8
bio.ras_0002.5
In addition , scaffold proteins have been shown to guide activation of specific effector pathway( s ) . For example , SHOC2 / Sur @-@ 8 bridges Ras and Raf to specifically enhance the Raf / MEK / ERK pathway without enhancing PI3K / AKT signaling ( 9 , 10 ) .
0-1.1 1-1.1 3-1.1.1.1.1.1 4-1.1.1.1.1 7-1.1.1 9-1.1.1.1 10-1.1.1.1.2 12-1.2.1.4.3 13-1.1.1.1.2.1.1 18-1.2 19-1.2 21-1.2.1.1.1.1.1 23-1.2.1.1.2.1.1 25-1.2.1.1.2.1.1 26-1.2.1 27-1.2.1.2.1.1 28-1.2.1.6.1.1.1 29-1.2.1.3.1.1 31-1.1.1.1.2.1.2 31-1.2.1.4.3 32-1.2.1.4 34-1.2.1.4.2.1.1 36-1.2.1.4.2.1.1 38-1.2.1.4.2.1.1 39-1.1.1.1.2.1 40-1.2.1.5.1 40-1.2.1.5.1.r 41-1.2.1.5 42-1.2.1.5.3.1.1.1 44-1.2.1.5.3.1.1.1 45-1.2.1.5.3 47-1.2.1.6.1.1.1.1 49-1.2.1.6.1.1.1.2
SDL-AMR-09
SDL-AMR-09
24885690
Expectedly , decreased serum concentrations led to lower proliferation rates in these cells , but exponential growth was sustained under all applied conditions .
2-1.1.1.2 3-1.1.1.1 4-1.1.1 5-1.1 6-1.1.2.r 7-1.1.2.1 7-1.1.2.1.2 7-1.1.2.1.2.r 8-1.1.2 10-1.1.2.1.1.r 11-1.1.2.1.1.1 12-1.1.2.1.1 14-1 15-1.2.1.1 16-1.2.1 18-1.2 20-1.2.2.2 21-1.2.2.1 22-1.2.2 22-1.2.2.r
a_pmid_2488_5690.50
PUMA
BRAF
EGFR
B-Raf
U2AF35
0-1.1.1.2.1.1 1-1.1.1.1 2-1.1.1 3-1.1 4-1.2.2 4-1.3.1.2 4-1.3.2 7-1.2.1.1 8-1.2.1 9-1.2.2 9-1.3.1.2 9-1.3.2 12-1.3.1.1.1 13-1.2.2 13-1.3.1.2 13-1.3.2 14-1.4.1.1.1.1.1 16-1.4.1.1.2.1.1 18-1.4.1.1.3.1.1.1 20-1.4.1.1.3.1.1.1 22-1.4.1 25-1.4.2.1.1.2 26-1.4.2.1.1.1.1 28-1.4.2.1.1.1.1 29-1.4.2.1
SDL-AMR-09
Eosinophils Human Superoxide production Human Transmigration through epithelial cells Human Transmigration through Matrigel Human CD11b @/@ CD18 ( Mac @-@ 1 ) translocation , degranulation Human IL @-@ 8 release
bel_pmid_1072_9607.18666
10729607
Taking into account the fact that lysates were of a mixture of tumour cells and surrounding stromal and infiltrating host cells , the immunoblotting of the tumour @-@ derived proteins showed similar results to those obtained using lysates of cultured cells .
SDL-AMR-09
15280923
6-1.1 12-1.1.1.1.1 13-1.1.1.1 13-1.1.1.2.1 14-1.1.1.2 15-1.1.1.2.1.2 17-1.1.1.2 18-1.1.1.2.2.2 19-1.1.1.2.2.1 20-1.1.1.2.2 23-1.2.1 24-1.2.1.1.r 26-1.2.1.1.1.1 28-1.2.1.1.1 29-1.2.1.1 30-1.2 31-1.2.2 31-1.2.2.1 31-1.2.2.1.r 32-1.2.2.1.1 32-1.2.2.1.1.2 32-1.2.2.1.1.2.r 32-1.2.2.2 35-1.2.2.1.1.1 37-1.2.2.1.1.1.1 38-1.2.2.1.1.1.1.1.r 39-1.2.2.1.1.1.1.1.1 40-1.2.2.1.1.1.1.1
pmid_1528_0923.70
ERK1
s2
C-Raf
Moreover , PLX4032 led to an increase in phosphorylation of FoxO1 @/@ 3A between 4 @–@ 10h after addition of compound ( not shown ) , which is known to promote its dissociation from DNA , and likely discards involvement of these factors as transcriptional regulators of HER3 in response to MAPK pathway inhibition .
SDL-AMR-09
bio.bmtr_0003.10
0-1 2-1.1.1.1.1 3-1.1 6-1.1.2 7-1.1.2.1.r 8-1.1.2.1 9-1.1.2.1.1.r 10-1.1.2.1.1.1.1 12-1.1.2.1.1.1.1 13-1.1.2.2.2 14-1.1.2.2.2.1.1 17-1.1.2.2 18-1.1.2.2.1 19-1.1.2.2.1.1.r 20-1.1.2.2.1.1 22-1.1.2.3.1 22-1.1.2.3.1.r 23-1.1.2.3 28-1.1.2.4.2 30-1.1.2.4 31-1.1.2.4.1.1 31-1.1.2.4.1.1.r 32-1.1.2.4.1 33-1.1.2.4.1.2.r 34-1.1.2.4.1.2.2.1 36-1.1.2.2.2 37-1.1.2.5.2 38-1.1.2.5 39-1.1.2.5.1 40-1.1.2.5.1.1.r 41-1.1.2.5.1.1.1 42-1.1.2.5.1.1 43-1.1.2.2.r 43-1.1.2.5.1.2.r 44-1.1.2.5.1.2.2 45-1.1.2.5.1.2 45-1.1.2.5.1.2.1 45-1.1.2.5.1.2.1.r 46-1.1.2.5.1.2.1.1.r 47-1.1.2.5.1.2.1.1.1.1 48-1.1.2.5.3.r 49-1.1.2.5.3 50-1.1.2.5.3.1.r 51-1.1.2.5.3.1.1.1.1 52-1.1.2.5.3.1.1 53-1.1.2.5.3.1
PAF
SDL-AMR-09
0-1.2.1.1 2-1.4 3-1.4 5-1 7-1.1.2.1.1 9-1.1.2.1.1 10-1.1.1 11-1.1 12-1.4 13-1.1.2.2.1.1 15-1.1.2.2.2.2.1.1.1.1 17-1.1.2.2.2 18-1.1.2.2.2.1 21-1.1.2.2.2.2.1.2 22-1.1.2.2.2.2 22-1.1.2.2.2.2.1 22-1.1.2.2.2.2.1.r 24-1.1.2.2.2.2.1.1.2 27-1.3.1.1 27-1.3.1.2 28-1.3.1.1.1 29-1.3.1 30-1.1.2.2.1.1
Mek , in turn , phosphorylates the N @-@ terminal acidic motif in C @-@ Raf , converting it to an allosteric activator of other Rafs ( Fig. 2B and C ) .
bio-kappa_0001.6
bio.bmtr_0002.15
To determine if this feedback model explains the activation of PI3K signaling in EGFR @-@ mutant cancers , we used shRNA to knockdown endogenous EGFR ( which carries an exon 19 deletion ) in the HCC827 NSCLC cell line and replaced with either EGFR ( exon 19 del ) wild @-@ type at T669 , or EGFR ( exon 19 del ) carrying a T669A mutation .
SDL-AMR-09
1-1.3 2-1.3.2.3.2.r 3-1.3.2.2.2 4-1.3.2.2.1 5-1.3.2.2 6-1.3.2 8-1.3.2.3 9-1.3.2.3.1.r 10-1.3.2.3.1.1.1 11-1.3.2.3.1.2 13-1.3.2.3.2.3.1.1.1 15-1.3.2.3.2.3 16-1.3.2.3.2.2.1 18-1.1.1 19-1.1 20-1.1.2.1.1 21-1.1.3.r 22-1.1.3 23-1.1.3.2.2 24-1.1.3.2.1.1 24-1.2.3.1.1.1 24-1.3.2.3.2.3.1.1.1 27-1.2.3.1.3 29-1.1.3.2.4.1 30-1.1.3.2.4.1.1 31-1.1.3.2 31-1.1.3.2.4 31-1.1.3.2.4.r 33-1.1.3.2.3.r 35-1.1.3.2.3.1.1 36-1.1.3.2.3.2.1.1 37-1.1.3.2.3 38-1.1.3.2.3 39-1 40-1.2 43-1.1.3.2.1.1 43-1.2.3.1.1.1 43-1.2.3.2.1.1 43-1.3.2.3.2.3.1.1.1 45-1.1.3.2.4.1 46-1.1.3.2.4.1.1 49-1.2.3.1.2 51-1.2.3.1.2 55-1.2.3 56-1.1.3.2.1.1 56-1.2.3.1.1.1 56-1.2.3.2.1.1 56-1.3.2.3.2.3.1.1.1 58-1.1.3.2.4.1 59-1.1.3.2.4.1.1 62-1.2.3.1.3 64-1.2.3.2.3.1 65-1.2.3.2.3 65-1.3.2.3.2.3
SDL-AMR-09
Our results show that in RKO this particular cancer cell trait is modulated by and dependent on B @-@ Raf @<sup> V600E </sup> and that targeting mutant <i> BRAF </i> is sufficient to restore sensitivity to caspase @-@ dependent apoptosis after serum withdrawal via p53 @-@ independent PUMA induction [ @<xref ref-type="bibr" rid="B27"> 27 </xref>@ ] .
24885690
a_pmid_2488_5690.67
0-1.1.2 0-1.1.2.r 1-1.1 1-1.1.1 1-1.1.1.r 2-1 5-1.2.1.3.1.1 6-1.2.1.1.2.3 7-1.2.1.1.2.2 8-1.2.1.1.2.1.1.2.1 9-1.2.1.1.2.1 10-1.2.1.1.2 12-1.2.1.1 14-1.2.1 15-1.2.1.2 17-1.2.1.1.1.1.1 19-1.2.1.1.1.1.1 21-1.2.1.1.1.2.1 23-1.2 23-1.2.1 23-1.2.1.r 24-1.2.r 25-1.2.2.1 26-1.2.1.1.1 26-1.2.1.1.1.2 26-1.2.1.1.1.2.r 26-1.2.2.1.1 26-1.2.2.1.1.2 26-1.2.2.1.1.2.r 28-1.2.2.1.1.1.1 31-1.2.2 33-1.2.2.2 34-1.2.2.2.2 35-1.2.2.2.2.1.r 36-1.2.2.2.2.1.1.1.1.1 38-1.2.2.2.2.1.1 39-1.2.2.2.2.1 40-1.2.2.2.2.1.2 41-1.2.2.2.2.1.2.1.1 42-1.2.2.2.2.1.2.1 44-1.2.2.2.2.1.3.2.2.1.1 46-1.2.2.2.2.1.3.2 46-1.2.2.2.2.1.3.2.1 46-1.2.2.2.2.1.3.2.1.r 47-1.2.2.2.2.1.3.1.1.1 48-1.2.2.2.2.1.3 51-1.2.2.2.2.1.3.3.1.1.1
bel_pmid_1074_4722.21132
Serine 15 in the N terminus of p53 has been shown to be the preferred ATM phosphorylation site ( 27 , 29 , 30 ) . As shown in Fig. 7A , ATM immunoprecipitated from irradiated cells was more active than that from control cells , and both ATM activities were inhibited by caffeine with IC50 at around 200 M.
10744722
0-1.1.1.3.2.1 1-1.1.1.3.1 4-1.1.1.3.3.1.1 5-1.1.1.3.3.1.2 7-1.1.1.3.3.2.1.1 9-1.1.1.3.r 10-1.1 12-1.1.1.3.r 14-1.1.1.2 15-1.1.1.1.1.1.1 16-1.1.1.1 17-1.1.1 19-1.1.2.1.1.1.1 21-1.1.2.1.1.1.2 23-1.1.2.1.1.1.3 27-1.2.3 28-1.2.3.1.r 29-1.2.3.1 30-1.2.3.1.1 32-1.2.1.3.1.1 33-1.2.1.1.2 33-1.2.1.3.2 34-1.2.1.1.2.1.r 35-1.2.1.1.2.1.1 36-1.2.1.1.2.1 38-1.2.1.2 39-1.2.1 40-1.2.1.3.r 42-1.2.1.3.2.1.r 43-1.2.1.3.2.1.1 44-1.2.1.3.2.1 46-1.2 46-1.2.2.2.1 48-1.2.1.1.1.1 48-1.2.1.3.1.1 49-1.2.2.2 51-1.2.2 52-1.2.2.1.r 53-1.2.2.1 57-1.2.2.1.1.2 58-1.2.2.1.1.2.1.1
SDL-AMR-09
P-TEFb
IL-3
threonine
1-1.2.1.1 1-1.3.3.2 2-1.2.1 3-1.2 4-1 5-1.3.r 7-1.3 7-1.3.3 7-1.3.3.r 8-1.3.2.1 10-1.3.3.1.r 11-1.3.3.1 13-1.1.r 14-1.1.1.1.1 16-1.1.2.1.1 17-1.1 18-1.1.3.1.1
bio.ras_0001.1
SDL-AMR-09
The most frequently mutated oncogenes in the deadliest cancers responsible for human mortality are KRAS , PIK3CA and BRAF .
0-1.1.2 1-1.1.1.1.1 2-1.1.1.1 3-1.1.1 4-1.1 4-1.1.3 6-1.1.3.r 7-1.1.3.r 10-1.1.3.1.r 12-1.1.3.1.1.1.1 14-1.1.3.1.2.1.1 15-1.1.3.1.1.1.2 15-1.1.3.1.2.1.2 17-1 17-1.4.1 19-1.2 20-1.2.1.r 21-1.2.1.1 22-1.2.1 24-1.3.r 25-1.3 27-1.3.2.1.1 29-1 29-1.4.1 31-1.4.1.1.1.2.1.1.1 33-1.4.1.1.1 33-1.4.1.1.1.2 33-1.4.1.1.1.2.r 36-1.5.1.1.1.1 38-1.5.1.1.1.2
Other less frequently observed mutations , such as those found in the G4 and G5 boxes , increase the rate of nucleotide exchange , thereby mimicking the GEFs and increasing the GTP - bound state ( 1 – 7 ) .
bio.ras_0001.10
SDL-AMR-09
Erk12
beta-catenin
beta-catenin
SDL-AMR-09
2-1.1.1.3 3-1.1.1.3 4-1.1.1.3.1.r 6-1.1.1.3.1 8-1.1.1.2.1.1 9-1.1 10-1.1.1 12-1.1.1.1.2 13-1.1.1.1 13-1.1.1.1.3.1.2.1 14-1.1.1.1.1.1 16-1.1.1.1.3 17-1.1.1.1.3.1.2.2 18-1.1.1.1.3.1.2.1.2.r 19-1.1.1.1.3.1.2.1.2 20-1.1.1.1.3.1.2.1.1.1 21-1.1.1.1.3.1.2.1.1.2 22-1.1.1.1.3.1.2.1.1.3 25-1.1.1.1.3.1 26-1.1.1.1.3.1.1.r 28-1.1.1.1.3.1.1.1.1 30-1.1.1.1.3.1.1.1.1 32-1.1.1.1.3.1.1.1.1 35-1 37-1.2 38-1.2.1 39-1.2.1.1.1.1.1 40-1.2.1.1 41-1.2.1.1.2.1.1 42-1.2.1.1.1 42-1.2.1.1.2 45-1.2.1.3 48-1.2.1.3.2
bio-kappa_0001.15
As a negative regulator of the pathway , PP2A can dephosphorylate the adapter protein Shc , required downstream of some tyrosine kinase receptors for the activation of the Raf / Mek / Erk module ; and it can dephosphorylate Mek and Erk proteins , thus inhibiting the cascade directly .
SDL-AMR-09
0-1.2.1 1-1.2 3-1.1 3-1.1.r 4-1 5-1.3.4 6-1.3.3 7-1.3.1.1.1 8-1.3.2 9-1.3
bio.bmtr_0003.9
This region does not contain any predicted FoxO binding sites .
ERK
0-1.1 1-1.1.1.r 2-1.1.1.1 3-1.1.1 4-1.3 5-1 6-1.2.1.1.2 7-1.2 8-1.2.2.1.2.1.1.1 10-1.2.2.1.2 11-1.2.1.1.1.1 11-1.2.2.1.1.1 12-1.2.1 12-1.2.2 15-1.4.2 16-1.4 19-1.4.1.2 20-1.4.1 23-1.4.1.3.1 24-1.4.1.3 26-1.5.1.1 26-1.5.1.2 28-1.5.1.1.1 29-1.5.1 30-1.5.1.2.1
SDL-AMR-09
bio.bmtr_0003.14
Knockdown of these factors modestly increased basal and PLX4032 @-@ induced HER2 levels , which likely contributes to the remarkable increase in pHER3 we observed ( Fig . 5D and 5E ) .
25
bio.mskcc_0001.50
1-1.4.1.1 2-1.4.1 3-1.4 5-1.1 6-1 7-1.3 8-1.2.r 9-1.2.1 10-1.2.1 14-1.2.1 18-1.2.1.5.1.1 20-1.2.1.5.1.1 22-1.2.2 23-1.2 30-1.2.1
SDL-AMR-09
Through metabolic labeling experiments , we find here that in addition to the S750 and T753 sites , B @-@ Raf is feedback phosphorylated on two other sites , S151 and T401 .
C-RAF
e2
1-1 2-1.1.r 3-1.1 4-1.1.1 6-1.2.1.1.1.1 7-1.2.1.1.1.2 8-1.2.1.1.2 8-1.2.2.3.1.3 10-1.2.1.1.2.1.1.1 11-1.2.1.1.2.1.1.2 12-1.2.1 13-1.2.1.2.2.1 14-1.2.1.2.2 15-1.2.1.2.2.r 16-1.2.1.2.3 17-1.2.1.2 17-1.2.1.2.1.1 19-1.2.1.3 20-1.2.1.3.1.r 21-1.2.1.3.1.1 22-1.2.1.3.1.1 24-1.2.1.3.1 26-1.2 29-1.2.2.4 29-1.2.2.4.1 29-1.2.2.4.1.r 30-1.2.2.4.1.1.1.r 30-1.2.2.4.r 32-1.2.2.1.2.1.1 34-1.2.2.1.1.1.1 36-1.2.2.1.1.2.1 39-1.2.1.1.2 39-1.2.2.1.3 41-1.2.1.1.2.1.1.1 42-1.2.1.1.2.1.1.2 43-1.2.2 44-1.2.2.2.2.1.1 45-1.2.2.2.2.1 46-1.2.2.2.2 47-1.2.2.2.2.r 48-1.2.2.2.3 49-1.2.2.2 49-1.2.2.2.1.1 51-1.2.2.3 52-1.2.2.3.1.r 53-1.2.2.3.1.2 54-1.2.2.3.1.2 56-1.2.2.3.1.1 56-1.2.2.3.1.1.r 58-1.2.2.3.1 61-1.2.2.1.2.1.1 62-1.2.1.1.2 62-1.2.2.1.3
As shown in Figure S1 , histone 2B phosphorylated by p38 SAPK had high levels of incorporated 32P , suggesting that p38 SAPK was active ; while under the same conditions , ASPP2 ( 693 @-@ 1128 ) fragment phosphorylated by p38 SAPK had very low levels of incorporated 32P , indicating that p38 SAPK is not an efficient kinase for ASPP2 phosphorylation .
bio.bmtr_0005.12
SDL-AMR-09
E2F
Raf-MAPK
Phelan
MDA-MB-468
18
GSK-3beta
K-Ras
ERK
EGFR
The proteins were then expressed in NIH 3T3 cells and examined for their abilities to alter cell morphology and induce focus formation .
bio.mskcc_0001.30
1-1.1.1 3-1.3 4-1.1 5-1.1.2.r 6-1.1.2.1.1 7-1.1.2.1.2 8-1.1.2 9-1 10-1.2 12-1.2.1.2.1.1 12-1.2.1.2.1.1.r 15-1.2.1.2.1 16-1.2.1.2.1.2.1 17-1.2.1.2.1.2 18-1.2.1.2 19-1.2.1.2.2 20-1.2.1.2.2.2.1 21-1.2.1.2.2.2
SDL-AMR-09
SDL-AMR-09
0-1.1.2.1.1 2-1.1.2.1.1 3-1.1.1 4-1.1 6-1.3 7-1 8-1.2.r 10-1.2.1 11-1.2
H @-@ Ras ubiquitination sites were also determined by the same approach .
bio.bmtr_0001.7
FoxO3A
Cdc12
bel_pmid_1073_7606.22816
10737606
Activation of the GFAP gene promoter by IL @-@ 11 and related cytokines Previous studies have shown that stimulation of gp130 molecules on neuroepithelial cells by LIF , CNTF , or the IL @-@ 6/sIL @-@ 6R complex induces activation of the GFAP gene promoter ( Bonni et al. , 1997 ; Nakashima et al. , 1999 b ) .
SDL-AMR-09
0-1.2 1-1.2.2.r 3-1.2.2.1.1.1.1 4-1.2.2.1.1 5-1.2.2 5-1.2.2.1 5-1.2.2.1.r 6-1.2.1.r 7-1.2.1.1.1.1 9-1.2.1.1.1.1 10-1.2.1 11-1.2.1.2.2 12-1.2.1.2.1.1 13-1.1.1.1 14-1.1.1 16-1.1 17-1.1.2.r 18-1.1.2.1 19-1.1.2.1.1.r 20-1.1.2.1.1.1.1 21-1.1.2.1.3.3 24-1.1.2.1.2 25-1.1.2.1.3.r 26-1.1.2.1.3.1.1.1 28-1.1.2.1.3.2.1.1 30-1.1.2.1.3 32-1.1.2.1.3.3.1.1.1 36-1.1.2.1.3.3.2.1.1 37-1.1.2.1.3.3 38-1.1.2 39-1.1.2.2 40-1.1.2.2.1.r 42-1.1.2.2.1.1.1.1.1 43-1.1.2.2.1.1.1 44-1.1.2.2.1 44-1.1.2.2.1.1 44-1.1.2.2.1.1.r 46-1.1.3.1.1.1.1.1.1 47-1.1.3.1.1.1 48-1.1.3.1.1.1.2.1 50-1.1.3.1.1.2.1 52-1.1.3.1.2.1.1.1.1 53-1.1.3.1 53-1.1.3.1.2.1 54-1.1.3.1.2.1.2.1 56-1.1.3.1.2.2.1
Ras
B-Raf
5D
CD18
HER2
NSCLC
cyclin D2
0-1.1.1.1 1-1.1.1 1-1.1.1.2 1-1.1.1.2.r 6-1.1.2.1 7-1.1.2 9-1 11-1.2 14-1.2.1.1.1.1 14-1.2.1.1.1.1.r 16-1.2.1.1.1 17-1.2.1.1.1.2.r 19-1.2.1.1.1.2.1.1.1 20-1.2.1.1.1.2 21-1.2.1.1.1.2.2.2 22-1.2.1.1.1.2.2 23-1.2.1.1.1.2.2.1.r 24-1.2.1.1.1.2.2.1.1.1.1 25-1.2.1.1.1.2.2.1 27-1.2.1.1 28-1.2.1.1.2.1 29-1.2.1.1.2 30-1.2.1.1.2.2.r 31-1.2.1.1.2.2.1.1 33-1.2.1.1.2.2.1.1 35-1.2.1.2 36-1.2.1.2.2.1.1.1 37-1.2.1.2.2 39-1.2.1
These results , along with the crystal structure , support a model in which mono @-@ ubiquitination at a Lys residue directly involved in GDP binding either enhances nucleotide exchange on K @-@ Ras , impairs GTP hydrolysis , or both .
bio.bmtr_0001.16
SDL-AMR-09
151
serine
-
hemin
GAP
Gammeltoft
Cancer
cancer
Our modeling and NMR analyses indicated that Ubiquitin dynamically samples a broad surface area of Ras that alters switch region dynamics .
bio.bmtr_0004.22
0-1.1.1.1 0-1.1.1.1.r 1-1.1.1 2-1.1 4-1.1.2 5-1 6-1.2.r 7-1.2.1.1.1 8-1.2.3 9-1.2 11-1.2.2.1.1 12-1.2.2.1 13-1.2.2 14-1.2.2.2.r 15-1.2.2.2.1.1 17-1.2.4 18-1.2.4.1.1.1 19-1.2.4.1.1 20-1.2.4.1
SDL-AMR-09
serine
actin
Ras
0-1 1-1 7-1.1.1.2 9-1.1.1.1.1.1.1 11-1.1.1.1.1.2.1.1.1.1.1 12-1.1.1.1.1.2.1.1 13-1.1.1.1.1.2.1.1.2.1 15-1.1.1.1.1.2.1.2.1 18-1.1 19-1.1.2.3 20-1.1.2.1 20-1.1.2.1.r 21-1.1.2.2.1.1.1 23-1.1.2.2.1.2.1.1.1.1.1 24-1.1.2.2.1.2.1.1 25-1.1.2.2.1.2.1.1.2.1 27-1.1.2.2.1.2.1.2.1 30-1.1.1 30-1.1.2 31-1.1.1.1 31-1.1.2.2 32-1.1.1.1.2.2.1.1.1.1 34-1.1.1.1.2.2.1 35-1.1.1.1.2.2.1.2.1.1 37-1.1.1.1.2.2 38-1.1.1.1.2.1.1.1 39-1.1.1.1.2
In addition , in co @-@ transfection experiments , Rlf ( Zwartkruis et al. , 1998 ) , but apparently not RalGDS ( Urano et al. , 1996 ) , can mediate Rap1 @- and C3G @-@ induced Ral activation .
SDL-AMR-09
bio.chicago_2015.19251
729
serine
e2
T669A
-
0-1.1 1-1 2-1.2.r 3-1.2.1.1.1 5-1.2.1.1.1 6-1.2 7-1.2.2.1.3 8-1.2.2.1 9-1.2.2.1.2.r 10-1.2.2.1.2.1.1 11-1.2.2 13-1.2.2.2 14-1.2.2.2.2.r 15-1.2.2.2.2.1.1 16-1.2.2.2.3.r 17-1.2.2.2.3.1.1.1.1 19-1.2.2.2.3.1 20-1.2.2.2.3.2.1.1 20-1.2.2.2.3.2.1.2 21-1.2.2.2.3
bel_pmid_1088_0513.7274
10880513
We show that IL @-@ 6 triggers selective activation of SHP2 and its association with RAFTK in Dex @-@ treated MM cells .
SDL-AMR-09
proline
l
Axin
Guichet
ERK2
K-Ras
threonine
753
SDL-AMR-09
However , mutation of the feedback sites significantly increased the transforming activities of B @-@ Raf proteins with intermediate or impaired kinase activity ( Fig . 4A ) .
bio.mskcc_0001.32
0-1 2-1.1.1 3-1.1.1.1.r 5-1.1.1.1.1 6-1.1.1.1 7-1.1.3 8-1.1 10-1.1.2.3 11-1.1.2.1 13-1.1.2.1.1.1.1 15-1.1.2.1.1.1.1 16-1.1.1.1 18-1.1.2.1.3 19-1.1.2 20-1.1.2.2.3 21-1.1.2.1.2 22-1.1.2.1 22-1.1.2.2 24-1.1.4.1 26-1.1.4.1.1
50
MAPK
5F
EGFR
SDL-AMR-09
bio.bmtr_0001.17
To corroborate this finding , we measure the activity of Ras by the GST @-@ RBD pull @-@ down assay .
1-1.4 2-1.4.2.2 3-1.4.2 3-1.4.2.1 3-1.4.2.1.r 5-1.1 6-1 8-1.2 9-1.2.1.r 10-1.2.1.1.1 11-1.3.r 13-1.3.1.1.1.1 15-1.3.1.1.1.1 16-1.3.1 18-1.3.1 19-1.3
Cancer
cancer
750
serine
p2
PUMA
V600E
SDL-AMR-09
siRNA @-@ mediated depletion of B @-@ Raf reduced cell proliferation by up to 65 % through the inhibition of ERK1 @/@ 2 activation , irrespective of the mutational status of B @-@ Raf .
bio.bel_0002.6
0-1.1.2.1.1.1 2-1.1.2 3-1.1 4-1.1.1.r 5-1.1.1.1.1 7-1.1.1.1.1 8-1 9-1.2.1 10-1.2 11-1.3.r 12-1.3 13-1.3 14-1.3.1.1 15-1.3.1 18-1.4 19-1.4.1.r 20-1.4.1.1.1.1 22-1.4.1.1.1.1 23-1.4.1 25-1.5 28-1.5.1.2 29-1.5.1 30-1.5.1.1.r 31-1.5.1.1 32-1.5.1.1 33-1.5.1.1
fascin
0-1.1.2.1.1 2-1.1.2.1.1 3-1.1.1 4-1.1 6-1.2 7-1 8-1.3.r 10-1.3.1 11-1.3
SDL-AMR-09
bio.ras_0003.6
H @-@ Ras ubiquitination sites were also determined by the same approach .
0-1.1.1 1-1.1 3-1 4-1.2.r 5-1.2.2 6-1.2.1.1 7-1.3 8-1.3
These residues are phosphorylated by activated ERK in vitro ,
bio.mskcc_0001.51
SDL-AMR-09
bel_pmid_1064_0734.39802
1-1.3.1 2-1.3 3-1.1 4-1 6-1.2.2 7-1.2.2.1.r 8-1.2.2.1.1.1 13-1.2.1.1.1.1.1 14-1.2.1.1.1.1.2 16-1.2.1.1.1.1.2 17-1.2.1.1.1.1.3 19-1.2.1.1.1.2.1.1.1 21-1.2.1.1 22-1.2.1 24-1.2.1.2 25-1.2.1.3 26-1.2.1.3.1.r 27-1.2.1.3.1.1.1.1 28-1.2.1.3.1 29-1.2.1.3.2.r 31-1.2.1.3.2.2 32-1.2.1.3.2.3.1.1 33-1.2.1.3.2.3.2 34-1.2.1.3.2 35-1.2.1.3.2.1.1 37-1.2.3 38-1.2.3.1.3.2.1 40-1.2.3.1.3.2 41-1.2.3.1.3.1 42-1.2.3.1.3 44-1.2.3.1.1 44-1.2.3.1.1.r 45-1.2.3.1 46-1.2.3.1.2.r 48-1.2.3.1.2.2.1.1.1 50-1.2.3.1.2.2 53-1.2.2.1.1.1 53-1.2.3.1.2.1.1
SDL-AMR-09
In this paper we demonstrate that expression of CD72 down @-@ modulates both extracellular signal @-@ related kinase ( ERK ) activation and Ca2+ mobilization induced by BCR ligation in the mouse B lymphoma line K46^mA , whereas BCR @-@ mediated ERK activation was not reduced by the ITIM @-@ mutated form of CD72 .
10640734
e2
RasGAP
a
1-1.1.2 2-1.1.1.1.1 3-1.1 5-1.3.1 5-1.3.1.r 6-1.3 6-1.3.1 6-1.3.1.r 7-1 8-1.2.r 10-1.2 11-1.2.1.r 12-1.2.1.1.1.1 13-1.2.1 14-1.2.1.2.1.1 16-1.2.1.3.1.2.1 17-1.2.1.3.1.2.2 18-1.2.1.3
<sec-title level="2"> Elevated ERK activity does not necessarily correlate with the status of EGFR and HER2 in breast cancer cells </sec-title>
15280923
SDL-AMR-09
pmid_1528_0923.72
SHP2
Phosphorylated endogenous ASPP2 was detected by the phospho @-@ specific antibody 30 minutes after RAS stimulation ( Figure 1D ) .
SDL-AMR-09
bmtr_0007.8
0-1.2.3 1-1.2.2 2-1.2.1.1 4-1 5-1.1.r 7-1.1.1.1 9-1.1.1 10-1.1 11-1.3.2.1 12-1.3.2.2 13-1.3 14-1.3.1.1.1.1 15-1.3.1 17-1.4.1 18-1.4.1.1
RasGEFs bind to Ras and lower the transition energy for the nucleotide exchange of the bound GDP for the more abundant cytosolic GTP , whereas RasGAPs bind to Ras and catalyze GTP hydrolysis .
bio.ras_0001.8
0-1.1.1.1.1.1 1-1.1.1 2-1.1.1.2.r 3-1.1.1.2.1.1 4-1.1 5-1.1.2 7-1.1.2.2.1 8-1.1.2.2 12-1.1.2.2.2 15-1.1.2.2.2.1 15-1.1.2.2.2.1.2 15-1.1.2.2.2.1.2.r 16-1.1.2.2.2.1.1.1 17-1.1.2.2.2.2.r 19-1.1.2.2.2.2.2.1 20-1.1.2.2.2.2.2 21-1.1.2.2.2.2.3 22-1.1.2.2.2.2.1.1 24-1 26-1.1.2.2.2.1 26-1.1.2.2.2.1.2 26-1.1.2.2.2.1.2.r 26-1.2.1 28-1.1.1.2.1.1 29-1.2 30-1.2.2 31-1.2.2.2.1 32-1.2.2.2
SDL-AMR-09
bel_pmid_1072_9607.19488
0-1.1.1.1.1.1.1 1-1.1.1 1-1.1.1.1 1-1.1.1.1.r 2-1.1.2.1.1.1.1.1.1 3-1.1 4-1.1.2.1.1.1.1.1.1 6-1.1.2.1.1.1.1.1.1 7-1.1.2.1 8-1.1.2.1.2.1.1.1.1 10-1.1.2.1.2.1.1.1.1 11-1.1.2 11-1.1.2.1.1.1 11-1.1.2.1.2.1 12-1.1.2.1.1 12-1.1.2.1.2 13-1.2.1 14-1.2 15-1.2.2.r 16-1.2.2.1.1.1 17-1.2.2 18-1.2.2.2.1.1.1 20-1.2.2.2.2.1.1 21-1.2.2.3.r 22-1.2.2.3.1.1 23-1.2.2.3 24-1.2.2.3.2.2 25-1.2.2.3.2 26-1.2.2.3.2.1 27-1.2.2.3.2.1
SDL-AMR-09
10729607
PAFR promoter 2 contained AP @-@ 2 and Sp @-@ 1 binding sites we demonstrated that PAF activates p44ERK1 @/@ p42ERK2 in CHO cells stably expressing PAF receptor
filamin
PLX4032
GATA-1
Dex
Ivanov
ERK
As expected from the heterogeneity seen in clinical specimens of breast cancer , there was variability in expression of EGFR , from high expression in MDA @-@ MB @-@ 468 and minimal expression in MDA @-@ MB @-@ 435 cells ( <xref ref-type="fig" rid="fig1"> Figure 1A </xref> ) .
15280923
SDL-AMR-09
1-1.4 2-1.4.1.r 5-1.4.1.1 6-1.4.1.1.1.r 7-1.4.1.1.1.1 8-1.4.1.1.1 10-1.4.1.1.1.2.2.1 11-1.4.1.1.1.2.2.2 17-1.1 17-1.2 18-1.1.1.r 19-1.1.1.1.1 21-1.4.1.1.1.2.r 22-1.2.2 23-1.2 25-1.2.1.1.1 27-1.2.1.1.1 29-1.2.1.1.1 31-1.3.2 32-1.3 34-1.3.1.1.1 36-1.3.1.1.1 38-1.3.1.1.1 39-1.2.1 39-1.3.1 42-1.5.1 43-1.5.1.1
pmid_1528_0923.74
0-1.6 1-1.6.1.1 2-1.6.1 4-1.1.1.1 6-1 7-1.3.r 9-1.3 10-1.2.r 12-1.2.1 13-1.2 18-1.4 19-1.4.r 21-1.5.2 22-1.5 23-1.5.1.r 24-1.5.1.r 25-1.5.1.1.1
bio-kappa_0001.18
SDL-AMR-09
Following ligand binding , Sos is brought from the cytoplasm to the activated receptor in a phosphotyrosine - dependent manner through adapter proteins such as Grb2 .
cdc2
bio.bmtr_0003.17
SDL-AMR-09
The increase in expression of HER3 after MAPK inhibition is due to activation of gene transcription , which was associated with a reduction of binding of the transcriptional repressors CTBP1 and CTBP2 to the HER3 gene promoter .
1-1.2 2-1.2.1.r 3-1.2.1 4-1.2.1.1.r 5-1.2.1.1.1.1 6-1.2.2 7-1.2.2.1.1.1.1 8-1.2.2.1 10-1 11-1 12-1.1 13-1.1.1.r 14-1.1.1.1 15-1.1.1 19-1.1.2 20-1.1.2.1.r 22-1.1.2.1 23-1.1.2.1.1.r 24-1.1.2.1.1 25-1.1.2.1.1.1.r 27-1.1.2.1.1.1.3 28-1.1.2.1.1.1.1 28-1.1.2.1.1.1.1.2 28-1.1.2.1.1.1.1.2.r 29-1.1.2.1.1.1.1.1.1 30-1.1.2.1.1.1 31-1.1.2.1.1.1.2.1.1 32-1 32-1.1.2.1.1.2.r 34-1.1.2.1.1.2.1.1.1.1 35-1.1.2.1.1.2.1.1 36-1.1.2.1.1.2 36-1.1.2.1.1.2.1 36-1.1.2.1.1.2.1.r
GAP-334
SDL-AMR-09
( c ) Axin inhibits secondary axis formation induced by CKI .
bio.chicago_2015.18464
1-1.1 3-1.2.1.1 4-1 5-1.3.1.1 6-1.3.1 7-1.3 8-1.3.2 9-1.3.2.1.r 10-1.3.2.1.1.1
147
lysine
-
C-Raf
bel_pmid_1069_9758.15770
which are dual @-@ specificity ( serine/threonine and tyrosine ) kinases that regulate downstream responses to a broad range of mitogenic , apoptotic , and differentiation @-@ inducing stimuli [ 368 @-@ 372 ] . Interestingly , MEK1 but not MEK2 is stimulated by H2O2 treatment , suggesting that only MEK1 is redox @-@ sensitive [ 154 ] .
2-1.1.1.1.2 4-1.1.1.1 7-1.1.1.1.1.1 8-1.1.1.1.1.1.2.2.1 10-1.1.1 12-1.1 13-1.1.3 14-1.1.2 17-1.1.2.1.2 18-1.1.2.1 19-1.1.2.1.1.r 20-1.1.2.1.1.1 22-1.1.2.1.1.2 25-1.1.2.1.1.3.1 27-1.1.2.1.1.3 28-1.1.2.1.1 30-1.1.4.1.1.1.1 32-1.1.4.1.1.1.2 35-1.2.3 35-1.2.4.2 37-1.2.1.2.2.1 38-1.2 39-1.2.2.1 39-1.2.2.1.r 40-1.2.2.3.2.1 42-1.2.1 42-1.2.2 43-1.2.1.1.r 44-1.2.1.1.1.2.1 45-1.2.1.1 47-1.2.4 48-1.2.4.1.r 49-1.2.4.1.3 50-1.2.4.1.1 52-1.2.4.1.2 54-1.2.4.1 56-1.2.4.3.1.1.1
10699758
SDL-AMR-09
-
367
345
MAPK1
bio.chicago_2015.17180
At the nucleus , PKC betaII mediates direct phosphorylation of the nuclear envelope polypeptide lamin B on sites involved in mitotic nuclear lamina disassembly ( 12 , 13 , 15 ) .
SDL-AMR-09
2-1.3 4-1.1.1.1 5-1.1.1.2 6-1 7-1.2.2 8-1.2 9-1.2.1.r 11-1.2.1.2.1 12-1.2.1.2 14-1.2.1.1.1 15-1.2.1.1.2 16-1.2.3.r 17-1.2.3 18-1.2.3.1 20-1.2.3.1.1.2.1 21-1.2.3.1.1.2.2 22-1.2.3.1.1.2 25-1.4.1.1.1.1 27-1.4.1.1.1.2 29-1.4.1.1.1.3
interrogative
B-Raf
p
0-1.3 2-1.1 3-1 4-1.2.1.1 5-1.2.1.2 6-1.2.1.3.2 7-1.2.1.3.1.1.1 8-1.2.1.3 9-1.2.1 10-1.2.1.4.r 11-1.2.1.4.1.1.1 12-1.2.1.4 13-1.2.1.4.2.1.1
SDL-AMR-09
bio.bmtr_0005.7
Interestingly , we observed two conserved putative MAPK phosphorylation sites in ASPP1 and ASPP2 .
ERK12
FGF signaling
ERK12
-
2
MTT
2
10
11
BRAF_gene
BRAF
Raf
RNA pol II
SDL-AMR-09
dSir2 Interacts Genetically with Hairy Embryos derived from mothers transheterozygous for hairy and dSir2 mated to wild @-@ type males exhibit moderate
0-1.1.1.1 1-1 2-1.3 3-1.2.r 4-1.2.1.1.1 5-1.2 6-1.2.2 7-1.2.2.1.r 8-1.2.2.1.1.1 9-1.2.2.1.2 10-1.2.2.1.2.1.r 11-1.2.2.1.2.1.1 12-1.2.2.1.2.1 13-1.1.1.1 14-1.2.2.1.3 15-1.2.2.1.3.1.r 16-1.2.2.1.3.1.1 18-1.2.2.1.3.1.1 19-1.2.2.1.3.1 20-1.2.2.1 20-1.2.2.1.4 20-1.2.2.1.4.r 21-1.2.2.1.4.1 21-1.2.2.1.4.1.1 21-1.2.2.1.4.1.1.r
bio.chicago_2015.17176
Ksr
s
bio.bmtr_0002.21
0-1.1 1-1 3-1.2 4-1.2.1.r 6-1.2.1.2.1 7-1.2.1.2.3.1.1 8-1.2.1.2 9-1.2.1.2.2.r 10-1.2.1.2.2.1.1 12-1.2.1 14-1.2.1.1.1 14-1.2.1.1.2 17-1.2.1.1.1.1.r 18-1.2.1.1.1.1.3.1.1 20-1.2.1.1 22-1.2.1.1.2.1.3.1.1
SDL-AMR-09
This supports the hypothesis that a dominant ERK feedback on ERBB3/PI3K/AKT is mediated though phosphorylation of T669 on EGFR ( or T677 HER2 ) .
pFopflash plasmid
Complex formation between B @-@ Raf and Pin1 correlated with the phosphorylation of B @-@ Raf on S/TP sites ( Fig . 1C ) and this interaction could be blocked when the MEK inhibitor U0126 was used to prevent ERK activation and the S/TP phosphorylation of B @-@ Raf ( Fig . 1D ) .
SDL-AMR-09
bio.mskcc_0001.12
0-1.1.1.1 1-1.1.1 3-1.1.1.2.1.1.1 5-1.1.1.2.1.1.1 6-1.1.1.2 7-1.1.1.2.2.1.1 8-1.1 9-1.1.2.r 11-1.1.2 12-1.1.2.1.r 13-1.1.2.1.1 14-1.1.2.1.1 15-1.1.2.1.1 18-1.1.2.1 20-1.1.3.1 22-1.1.3.1.1 24-1 27-1.2 29-1.2.1 32-1.2.2.1.2.1.1.1 33-1.2.2.1 33-1.2.2.1.2 33-1.2.2.1.2.r 34-1.2.2.1.1.1 36-1.2.2 38-1.2.2.2 39-1.2.2.2.2.1.1.1.1 40-1.2.2.2.2.1 41-1.2.2.2.2 44-1.2.2.2.2.2 46-1.1.1.2.1.1.1 48-1.1.1.2.1.1.1 50-1.2.3.1 52-1.2.3.1.1
serine
827
2+
C-Raf
hCdc14 phosphatase
B-Raf
A polyclonal antibody NGH.S4 was purified by affinity column purification .
1-1.2.2 2-1.2 3-1.2.1.1 5-1 5-1.1 6-1.1.r 7-1.1.1 8-1.1.2 9-1.1
bmtr_0007.3
SDL-AMR-09
SDL-AMR-09
0-1.1.1 0-1.1.1.r 1-1.1 2-1.1.2.r 4-1.1.2 5-1.1.2.1.r 6-1.1.2.1.1.1.1 7-1.1.2.1 9-1 12-1.1.3.r 14-1.1.3 15-1.1.3.1 17-1.1.3.1.3 18-1.1.3.1.1.1.1 21-1.1.2.1.1.2.1.1.1 21-1.1.3.1.2.1.1 22-1.1.3.1 24-1.2.1 26-1.2.1.1
bio.bmtr_0004.6
No increase in the rate of GTP hydrolysis was observed for mUbRas in the presence of the same GAP @-@ to Ras ratio ( Fig . 5b ) .
ATM
PKCa
V600E
PKC
Cancer
cancer
pmid_1528_0923.80
SDL-AMR-09
15280923
Six cell lines with different levels of EGFR expression were selected for treatment with PKI166 .
0-1.1.1 1-1.1 2-1.1 4-1.3.1 5-1.3 6-1.3.2.r 7-1.3.2.1.1.1 8-1.3.2 10-1 11-1.2.r 12-1.2 13-1.2.1.r 14-1.2.1.1.1
SDL-AMR-09
0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 2-1 4-1.2 6-1.2.1.1.2 7-1.2.1.1 8-1.2.1 9-1.2.1.2.1.1.1 10-1.2.1.2
bio.mskcc_0001.20
These findings support a model whereby feedback phosphorylation disrupts Raf heterodimerization .
bio.chicago_2015.18163
SDL-AMR-09
1-1.4 2-1.4.1.r 3-1.4.1.1 3-1.4.1.2 3-1.4.1.3 4-1.4.1.3.1 6-1.4.1.1.1 7-1.4.1 8-1.4.1.2.1 12-1.3 17-1.1 18-1.1.1 19-1.1.1.1.r 19-1.1.2.r 20-1.1.1.1.1.1.1.1 23-1.1.1.1 24-1 25-1.2.2 26-1.2.1.1.1.1 27-1.2.1 28-1.2 31-1.2.3 32-1.2.3.1.r 33-1.2.3.1.1 35-1.2.3.1.1 36-1.2.3.1 37-1.2.3.1.2.r 39-1.2.3.1.2 40-1.2.3.1.2.1.r 41-1.2.3.1.2.1.1.1
As demonstrated in Figure 5 , B and C , in the absence of neurotrophins , DRG neurons derived from NF1 @-@ deficient embryos exhibit elevated erk phosphorylation levels that are comparable to wild @-@ type neurons in the presence of NGF .
STAT
-
hKSR-2
pmid_1528_0923.111
SDL-AMR-09
1-1.3.1.1.1 2-1.3 3-1.3.2.1.1 5-1.3.2.1.1 7-1.3.2.1.1 8-1.3.1 8-1.3.2 10-1.1 11-1.1.1.r 13-1.1.1 13-1.1.1.1 13-1.1.1.1.r 14-1.4.1 15-1.4 16-1 17-1.2.1.1.1 19-1.2.1.1.1 20-1.2 21-1.5 22-1.5.2.1 23-1.5.2.2 24-1.5.1 26-1.6.r 27-1.6.1.2 27-1.6.2.2 28-1.6.1 28-1.6.2 29-1.6.1.4 30-1.6.1.4.1.1 31-1.6.1.4.1.2 33-1.6.1.3.1.1 35-1.6.1.3.2.1 36-1.6.1.3.1 36-1.6.1.3.2 36-1.6.2.3.1 37-1.6.1.1.r 38-1.6.1.1.1.2.1 45-1.6.1.1.1.1.1 45-1.6.2.1.1.1.1 46-1.6 46-1.6.2.1 47-1.6.1.1.2.2.1 54-1.6.1.1.2.1.1 56-1.6 57-1.6.2.3.1.1 59-1.6.2.3.2.1 60-1.6.2.3.2 69-1.6.1.1.1.1.1 69-1.6.2.1.1.1.1 70-1.6 71-1.6.1.1.2.2.1 78-1.6.1.1.2.1.1 81-1.7.1 82-1.5.2.1 82-1.7.1.1
For SUM149 and MDA @-@ MB @-@ 468 cells the combination of the inhibitors almost completely eliminated ERK1 @/@ 2 phosphorylation after 1 h incubation , although growth inhibition over 72 h was 54 @–@ 63 % with 0.5 <i> μ </i>@ <sc> M </sc> PKI166 plus 10 <i> μ </i>@ <sc> M </sc> U0126 , and 63 @–@ 81 % with 5.0 <i> μ </i>@ <sc> M </sc> PKI166 plus 10 <i> μ </i>@ <sc> M </sc> U0126 ( <xref ref-type="table" rid="tbl1"> Table 1 </xref> ) .
15280923
SKBR3
2+
0-1.1.1.1.1 0-1.2.3.3.1.1 1-1.1 4-1.1.2 6-1.1.3.1.1.1.1 6-1.2.3.3.2.1.2.1.1.1 8-1.2.3.3.2.1.2.1.1.1 9-1.1.3.2.1.1.1.1.1 9-1.2.3.3.2.1.1.1.1 10-1.1.3.1 11-1.1.3 12-1.1 12-1.1.3.2 14-1.2.3.3.2.1.1.1.1 18-1.2.3.3.2.1.2 21-1.2.3 22-1.2.3.1 22-1.2.3.1.r 23-1.2.3.3.1.1 26-1.2.3.3 26-1.2.3.3.2 26-1.2.3.3.2.r 28-1.2.3.3.2.1.2.1.1.1 30-1.2.3.3.2.1.2.1.1.1 32-1.1.3.2.1.1 32-1.2.3.3.2.1.2 33-1.2.3.3.2.1.1.1.1 35-1.2.3.3.2.1.1.1.1 36-1.2.3.3.2.1 38-1.2.1 39-1.2 39-1.2.3.r 41-1.2.2.1.1.1 42-1.2.2 43-1.2.2.2.1.1 44-1.2.2.1.2.1.1.1 45-1.2.2.1 45-1.2.2.1.2 45-1.2.2.1.2.r
SDL-AMR-09
LiCl Activates a Prosurvival Pathway through GSK @-@ 3 beta Inhibition and Activation of beta @-@ Catenincf @-@ mediated Transcription-- To determine whether LiCl had an effect on GSK @-@ 3 @-@ mediated beta @-@ catenin signaling , we used the pTopflash or pFopflash luciferase reporter plasmids .
bio.chicago_2015.18003
0-1.3.2 1-1.3.1 2-1.3 5-1.1.1.2.1 6-1.1.1 6-1.1.1.2 6-1.1.1.2.r 8-1.1.1.1.1 10-1.1.1.1.1 11-1.1.3 12-1.1 13-1.1.2 13-1.1.2.1 13-1.1.2.1.r 14-1.1.2.2.r 15-1.1.2.2.2.1 17-1.1.2.2.2 18-1.1.2.2.1 19-1.1.2.2 20-1.1.4.r 21-1.1.4.1.1 22-1 24-1.2.1 27-1.2.1.1 27-1.2.1.1.2 27-1.2.1.1.2.r 29-1.2.1.1.1.1 32-1.2 34-1.2.2 35-1.2.2.2.3 36-1.2.2.2.4 37-1.2.2.2 38-1.2.2.2.2.r 39-1.2.2.2.2 40-1.2.2.3.r 42-1.2.2.3 45-1.3.3.1 46-1.3.3.1.1.1 47-1.3.3.1.1 50-1.3.3.1.1.2.1.1.1
24885690
a_pmid_2488_5690.53
SDL-AMR-09
Here we show that the V600E mutation of B @-@ Raf also provides independency of serum @-@ derived growth signals in RKO and that targeting of oncogenically mutant <i> BRAF </i> is sufficient to deprive this vital feature of malignancy from the cells , thereby corroborating previous reports [ @<xref ref-type="bibr" rid="B6"> 6 </xref>@ ] .
SDL-AMR-09
Apoptosis was confirmed by the detection of cleaved caspase 3 at considerable levels in serum @-@ starved RBW @-@ 1 , while all other samples showed full @-@ length protein only ( Figure <xref ref-type="fig" rid="F2"> 2 </xref>@ H ) .
a_pmid_2488_5690.60
0-1.1.2 2-1.1 3-1.1.1.r 5-1.1.1 6-1.1.1.1.r 7-1.1.1.1.1.2 8-1.1.1.1.1.1.1 9-1.1.1.1.1.1.2 11-1.1.1.1.2 12-1.1.1.1 13-1.1.1.2.r 14-1.1.1.2.2.1 16-1.1.1.2.2 17-1.1.1.2.1.1 19-1.1.1.2.1.1 21-1 22-1.2.1.1 23-1.2.1.2 24-1.2.1 24-1.2.1.3 24-1.2.1.3.r 25-1.2 26-1.2.2.1.1 28-1.2.2.1 29-1.2.2 30-1.2.3 32-1.3.1
24885690
GTP
HER2
BRAF
K46^mA
6
bio.mskcc_0001.25
Not surprisingly , given that mutation of the S365 14 @-@ 3 @-@ 3 binding site enhances the membrane localization of B @-@ Raf ( 2 ) , increased heterodimerization with C @-@ Raf was observed for S365A B @-@ Raf compared to WT B @-@ Raf ( Fig . 3F ) .
SDL-AMR-09
0-1.1.4.1 0-1.1.4.1.r 1-1.1.4 5-1.1.1.1 5-1.1.1.1.2 5-1.1.1.1.2.r 5-1.1.3.1.1 9-1.1.3.1.1.1.3.1.1.1 11-1.1.3.1.1.1.3.1.1.1 13-1.1.3.1.1.1.3.1.1.1 14-1.1.3.1.1.1.3 16-1.1.3.1 18-1.1.3.1.2.2 19-1.1.3.1.2 21-1.1.2.1.1.1 23-1.1.1.2.1.1 25-1.1.3.1.3.1.1.1 28-1.1 29-1.1.1 29-1.1.2 31-1.1.1.2.1.1 33-1.1.1.1.1.1 33-1.1.1.2.1.1 35-1 37-1.1.1.1.2.1 38-1.1.1.1.1.1 40-1.1.1.1.1.1 41-1.1.2.r 43-1.1.2.1.2 44-1.1.1.1.1.1 44-1.1.2.1.1.1 46-1.1.1.1.1.1 46-1.1.2.1.1.1 48-1.1.5.1 50-1.1.5.1.1
bio.chicago_2015.17655
We may conclude that GAGA factor binds to ( CT ) n repeats independently of TBP binding and facilitates binding of the latter directly or indirectly .
SDL-AMR-09
0-1.1.1 1-1 2-1.1 3-1.1.2.r 4-1.1.2.1.1.1.1 5-1.1.2.1.1.1.2 6-1.1.2.1.3.2 12-1.1.2.1.2.1.2 13-1.1.2.1.3.1 15-1.1.2.1.3.2.1.1.1 16-1.1.2.1 16-1.1.2.1.3.2 17-1.1.2 18-1.1.2.2 19-1.1.2.2.2 23-1.1.2.2.2.2 23-1.1.2.2.2.3 25-1.1.2.2.2.3 25-1.1.2.2.2.3.1 25-1.1.2.2.2.3.1.r
6
DNA
DNA
bio.bmtr_0002.2
0-1.1 1-1 2-1.2.r 4-1.2.1.1.1.1.1 6-1.2.1.1.1.1.1 7-1.2.1.1.1 8-1.2.1 9-1.2.1.1 12-1.2.1.1.2 12-1.2.1.1.3 13-1.2.1.1.2.1.r 14-1.2.1.1.2.1.1.1 16-1.2.1.1.3.3 17-1.2.1.1.3 19-1.2.1.1.3.2.1.1.1 19-1.2.1.1.3.2.2.1.1 20-1.2.1.1.3.2.1.1.2 20-1.2.1.1.3.2.2.1.2 21-1.2.1.1.3.2.r 22-1.2.1.1.3.2.1.2.1.1 23-1.2.1.1.3.2 24-1.2.1.1.3.2.2.2.1.1 26-1.2 27-1.2.r 28-1.2.2.1.3.1.2.3 29-1.2.2 30-1.2.2.1.4.r 32-1.2.2.1.2 33-1.2.2.1.1.1.1.1.1.1 34-1.2.2.1.1.1 34-1.2.2.1.1.1.1 34-1.2.2.1.1.1.1.r 36-1.2.2.1.1 37-1.2.2.1 38-1.2.2.1.3 40-1.2.2.1.3.1.1.1.1 41-1.2.2.1.3.1 43-1.2.2.1.3.1.2.3 44-1.2.2.1.3.1.2.2.1
We hypothesized that the MEK @/@ ERK pathway may suppress trans @-@ phosphorylation of ERBB3 by directly phosphorylating the JM domains of EGFR and HER2 , and that this could be a dominant MEK inhibitor @-@ induced feedback leading to AKT activation in these cancers .
SDL-AMR-09
Mitogen-activated_protein_kinase_kinase
MEK
HER3
4A
SDL-AMR-09
bio.bmtr_0002.6
Together these data indicate that loss of this inhibitory threonine phosphorylation on the JM domains of EGFR and HER2 occurs in cancer cell lines following MEK inhibition , presumably due to differential subcellular localization and @/@ or binding proteins .
0-1.1.2 1-1.1.1 2-1.1 3-1 4-1.2.r 5-1.2 6-1.2.1.r 7-1.2.1.3 8-1.2.1.2 9-1.2.1.1.1.1 10-1.2.1 13-1.2.1.1.2.1.1 14-1.2.1.1.2.1.2 16-1.2.1.1.2.2.1.1.1 18-1.2.1.1.2.2.2.1.1 20-1.2.2.r 21-1.2.2.1.2.1 22-1.2.2 22-1.2.4.1.1.1 23-1.2.2 24-1.2.3 25-1.2.3.1.1.1.1 26-1.2.3.1 28-1.2.4.2 29-1.2.4 30-1.2.4 31-1.2.4.1.1 31-1.2.4.1.1.2 31-1.2.4.1.1.2.r 31-1.2.4.1.2.2 34-1.2.4.1 36-1.2.1.1.2.2 36-1.2.4.1 37-1.2.4.1.2.1 38-1.2.4.1.2
Sp-1
B
We found that STAT3 , but not STAT5 , was activated in response to IGF @-@ I in 293T cells cotransfected with IGF @-@ IR and STAT expression vectors . Moreover , tyrosine phosphorylation of STAT3 , JAK1 , and JAK2 was increased upon IGF @-@ I stimulation of endogenous IGF @-@ IR in 293T cells transfected with the respective STAT or JAK expression vector .
SDL-AMR-09
0-1.2.1 1-1.2 2-1.2.2.r 3-1.2.2.1.1.1.1 5-1.2.2 6-1.2.2.2.1 6-1.2.2.2.1.r 7-1.2.2.2.2.1.1 10-1.2.2.1 10-1.2.2.2 11-1.2.2.1.2.r 12-1.2.2.1.2 13-1.2.2.1.2.1.r 14-1.2.2.1.2.1.1.1 16-1.2.2.1.2.1.1.1 18-1.2.2.1.2.1.2.1.1 19-1.2.2.1.2.1.2 20-1.2.2.1.2.1.2.2 21-1.2.2.1.2.1.2.2.1.r 22-1.2.2.1.2.1.2.2.1.1.1.1 24-1.2.2.1.2.1.2.2.1.1.1.1 25-1.2.2.1.2.1.2.2.1 26-1.2.2.1.2.1.2.2.1.2.1.1.1.1 27-1.2.2.1.2.1.2.2.1.2.1 28-1.2.2.1.2.1.2.2.1.2 30-1.1.1.1.1 30-1.2.2.1.2.1.2.2.1 32-1.1.1.1.1.1.1.1 32-1.1.1.1.1.2.1.1 32-1.1.1.1.1.3.1.1 33-1.1.1.1 34-1.1.1.1.1.r 35-1.1.1.1.1.1.2.1.1 37-1.1.1.1.1.2.2.1.1 40-1.1.1.1.1.3.2.1.1 42-1.1.1 44-1.1.1.2.1.1.1 46-1.1.1.2.1.1.1 47-1.1.1.2 48-1.1.1.2.2.r 49-1.1.1.2.2.2 50-1.1.1.2.2.1.1 52-1.1.1.2.2.1.1 54-1.1.1.2.2.3.1.1 55-1.1.1.2.2.3 56-1.1.1.2.2.3.2 57-1.1.1.2.2.3.2.1.r 59-1.1.1.2.2.3.2.1.1.1.1.2 60-1.1.1.2.2.3.2.1.1.1.1.1.1 61-1.1.1.2.2.3.2.1 62-1.1.1.2.2.3.2.1.2.1.1.1.1 63-1.1.1.2.2.3.2.1.1.1 63-1.1.1.2.2.3.2.1.2.1 64-1.1.1.2.2.3.2.1.1 64-1.1.1.2.2.3.2.1.2
10747872
bel_pmid_1074_7872.20016
Eluting in HPLC fractions 78 to 79 was a peptide phosphorylated on S750 and T753 , the previously identified ERK sites , and eluting in fractions 26 and 58 to 59 were peptides phosphorylated at S151 and T401 , respectively .
SDL-AMR-09
0-1.1 3-1.1.2 4-1.1.2.1.1 6-1.1.2.1.2 9-1.1.1 10-1.1.1.1.4 17-1.1.1.1.3.2.1 18-1.1.1.1.3.2 19-1.1.1.1.3.1.1.1 20-1.1.1.1.3 22-1 23-1.1 23-1.2 23-1.3 25-1.1.2 25-1.2.2 25-1.3.2 26-1.2.2.1 27-1.1.2.1 27-1.3.2.1 28-1.3.2.1.1 30-1.3.2.1.2 32-1.1.1 32-1.2.1 32-1.3.1 33-1.1.1.2.3 36-1.3.2.1
bio.mskcc_0001.14
casein kinase I
Chk2
0-1.1.1.1 2-1.1.1 3-1.1 4-1 5-1.2.r 6-1.2.1 7-1.2.1.1.r 8-1.2.1.1.1.1 9-1.2 10-1.2.2.1 10-1.2.2.2 13-1.2.2.1.1.r 14-1.2.2.1.1.3.1.1 15-1.2.2 17-1.2.2.2.1.3 20-1.2.2.2.1.4.1.1 22-1.3.1 23-1.3.1.1
Phospho @-@ specific antibodies confirmed that treatment with AZD6244 inhibited phosphorylation of T669 of EGFR and the analogous T677 of HER2 ( Figure 5A ) .
SDL-AMR-09
bio.bmtr_0002.5
SDL-AMR-09
3-1.1.1.1.1.1 4-1.1.1 5-1.1.1.2.1.1 7-1 9-1.1 11-1.1.2.4.1.1.1 13-1.1.2.4.1.1.1 15-1.1.2.4 16-1.1.2.1.1.1 17-1.1.2 18-1.1.2.2.r 19-1.1.2.2.1.1 20-1.1.2.3.r 21-1.1.2.3.1.1 22-1.1.2.3
10747872
Dominant @-@ negative JAK1 or JAK2 was able to block the IGF @-@ IR @-@ mediated tyrosine phosphorylation of STAT3 in 293T cells .
bel_pmid_1074_7872.21262
1
bio.bmtr_0002.12
2-1.6 4-1.1 5-1 6-1.2.1.1.1 8-1.2.1.1.1 9-1.2 10-1.2.2 11-1.2.2.1.1.1 12-1.2.2.1.2.1 13-1.3.r 14-1.3.1.1 15-1.3 17-1.4 18-1.4.2.2 19-1.4.2.1.1.1 20-1.4.2 22-1.5.1 23-1.5.1.1 26-1.4.3 27-1.4.3.1.r 29-1.4.3.1.2 30-1.4.3.1.2.1.r 31-1.4.3.1.2.1 33-1.4.3.1.2.1.1 33-1.4.3.1.3.2.2 35-1.4.3.1.3.2.1.1 36-1.4.3.1.2.1.2.r 37-1.4.3.1.2.1.2.1.1.1.1 38-1.4.3.1.2.1.2.1.1.2.1 39-1.4.3.1.2.1.2.1 40-1.4.3.1.2.1.2 41-1.4.3.1.2.1.3 42-1.4.3.1.2.1.3.1.1.1.1 43-1.4.3.1.2.1.3.1 45-1.4.3.1.1 45-1.4.3.1.1.r 46-1.4.3.1.4 47-1.4.3.1 48-1.4.3.1 50-1.4.3.1.3 51-1.4.3.1.3.1.r 53-1.4.3.1.3.1 55-1.4.2 55-1.4.3.1.3.2.2 57-1.4.2.1.1.1 57-1.4.3.1.3.2.1.1
As a control , we treated CHO @-@ KI cells expressing EGFR T669A with HRG ligand to induce maximal ERBB3 phosphorylation ( Figure 6A ) , indicating that the lack of induction of phospho @-@ ERBB3 in EGFR T669A expressing cells following MEK inhibition was not simply due to the saturation of the system with phospho @-@ ERBB3 .
SDL-AMR-09
SDL-AMR-09
We obtained similar results using K @-@ Ras ( Supplementary Figure 6 ) , indicating that the effects of monoubiquitination on Ras are not isoform @-@ specific .
0-1.1 1-1 2-1.2.2 3-1.2 3-1.2.1 3-1.2.1.r 4-1.3 5-1.3.2.1.1 7-1.3.2.1.1 9-1.2.3.1.2 10-1.2.3.1 11-1.2.3.1.1 14-1.2.4 15-1.2.4.1.r 17-1.2.4.1.2 18-1.2.4.1.2.1.r 19-1.2.4.1.2.1 19-1.2.4.1.2.1.1 19-1.2.4.1.2.1.1.r 20-1.2.4.1.2.2.r 21-1.2.4.1.2.2.1.1 23-1.2.4.1.1 23-1.2.4.1.1.r 24-1.2.4.1.3 26-1.2.4.1
bio.bmtr_0004.8
832
824
13.434
Knockdown of these factors modestly increased basal and PLX4032 - induced HER2 levels , which likely contributes to the remarkable increase in pHER3 we observed ( Fig. 5D and 5E ) .
0-1.1 1-1.1.1.r 2-1.1.1.1 3-1.1.1 4-1.3 5-1 6-1.2.1.1.2 7-1.2 8-1.2.2.1.2.1.1.1 10-1.2.2.1.2 11-1.2.1.1.1.1 11-1.2.2.1.1.1 12-1.2.1 12-1.2.2 15-1.4.2 16-1.4 19-1.4.1.3 20-1.4.1 23-1.4.1.2.1 24-1.4.1.2 26-1.5.1.1 26-1.5.1.2 27-1.5.1.1.1 28-1.5.1 29-1.5.1.2.1
SDL-AMR-09
bio-exp_0001.13
-
Ras
b-ZIP
GTP
GEF
Cancer
cancer
C3G
CD72
C-RAF
AG
GEF
p2
0-1.2 1-1 4-1.1.r 5-1.1.1.1.1.1 6-1.1.1 7-1.1.1.2 8-1.1.1.2.1.r 10-1.1.1.2.1.1.1 11-1.1.1.2.1 12-1.1.1.2.2.r 14-1.1.1.2.2.1 15-1.1.1.2.2 16-1.1.1.2.3.r 18-1.1.1.2.3 20-1.1.2 21-1.1.2.2 22-1.1.2.2.1.r 23-1.1.2.2.1.1 24-1.1.2.2.1 30-1.1.2.3.1.1.1 33-1.1 35-1.1.3 36-1.1.3.2.r 38-1.1.3.2.2 39-1.1.3.2.3 40-1.1.3.2 41-1.1.3.2.4.r 43-1.1.3.2.4.1 45-1.1.3.2.4 46-1.1.3.2.4.2.r 48-1.1.3.2.4.2.1 49-1.1.3.2.4.2
Other possibilities would be that actin promotes interaction of the BR particle with a fibrous network in the nucleoplasm , allows binding to export receptors ( cf . ref . 52 ) , or is involved in the dramatic conformational change of the particle upon translocation through the nuclear pore .
bio.chicago_2015.19160
SDL-AMR-09
RASMAPK
SDL-AMR-09
bio.chicago_2015.18798
Furthermore , during early gastrulation , DLT normally colocalizes with CRB .
0-1 0-1.1.1 2-1.1.3.r 3-1.1.3.1 6-1.1.1.1.1.1 7-1.1.2 8-1.1 9-1.1.1.r 10-1.1.1.2.1.1
high amounts of Dpp signaling abolish brk transcription completely , intermediate amounts of Dpp only partially repress brk transcription , while the absence of Dpp results in high levels of brk transcription .
0-1.1.1.1.2 1-1.1.1.1 2-1.1.1.1.1.r 3-1.1.1.1.1.1.1.1 4-1.1.1.1.1 5-1.1.1 6-1.1.1.2.1.1.1 7-1.1.1.2 8-1.1.1.3 10-1.1.2.1.1 11-1.1.2.1 12-1.1.2.1.2.r 13-1.1.2.1.2 14-1.1.2.3.1 15-1.1.2.3 15-1.1.2.3.r 16-1.1.2 17-1.1.2.2 18-1.1.2.2 20-1 22-1.2.1 23-1.2.1.1.r 24-1.2.1.1 25-1.2 26-1.2.2.r 27-1.2.2.2 28-1.2.2 29-1.2.2.1.r 30-1.2.2.1 31-1.2.2.1
bio.chicago_2015.19269
SDL-AMR-09
BMP-1
SDL-AMR-09
In contrast , no differential sensitizing effect was observed for conventional chemotherapeutic agents ( mitomycin C , oxaliplatin , paclitaxel , etoposide , 5 @-@ fluorouracil ) , nor for the targeted agents cetuximab , sorafenib , vemurafenib , RAF265 , or for inhibition of PI3 kinase .
1-1 3-1.1.1.1 3-1.1.1.1.r 4-1.1.1.4 5-1.1.1.3 6-1.1.1 8-1.1 9-1.1.1.2.r 10-1.1.1.2.1.1 11-1.1.1.2.1.2 12-1.1.1.2.1 14-1.1.1.2.1.3.1.1.1.1 15-1.1.1.2.1.3.1.1.1.2 17-1.1.1.2.1.3.1.2.1.1 19-1.1.1.2.1.3.1.3.1.1 21-1.1.1.2.1.3.1.4.1.1 23-1.1.1.2.1.3.1.5.1.1 25-1.1.1.2.1.3.1.5.1.1 28-1.1.1.1.r 31-1.1.1.2.2.1 32-1.1.1.2.2 33-1.1.1.2.2.2.1.1.1.1 35-1.1.1.2.2.2.1.2.1.1 37-1.1.1.2.2.2.1.3.1.1 39-1.1.1.2.2.2.1.4.1.1 43-1.1.1.2.3 44-1.1.1.2.3.1.r 45-1.1.1.2.3.1.1.1 46-1.1.1.2.3.1
24885690
a_pmid_2488_5690.12
Cancer
cancer
SDL-AMR-09
pmid_1528_0923.102
0-1.1 1-1.1.1.r 2-1.1.1.1.1 3-1.1.1.2 4-1.4 5-1 7-1.2 8-1.2.1.r 9-1.2.1.1.1 11-1.2.1.1.1 13-1.2.1.1.1 20-1.5.1.2 23-1.5.2.1 24-1.5.2 26-1.3.1.1 28-1.3.2.1 29-1.3.1 29-1.3.2 30-1.6.r 32-1.6.1.1 34-1.6.2.1 35-1.6.1 35-1.6.2 37-1.6.3.1.1 38-1.6.3 41-1.6.3.2.1 42-1.6.3.1 42-1.6.3.2 45-1.7 47-1.7.1 48-1.7.1.1
Treatment with U0126 alone significantly increased the numbers of MDA @-@ MB @-@ 231 in the G @<sub> 1 </sub> phase of the cell cycle ( 89 @–@ 93 % compared with 70 @–@ 72 % of control or PKI 166 treated cells , <i> P </i>@ < 0.001 ) .
15280923
1996
HER2
bio.mskcc_0001.36
4-1.1.2.2 7-1.1.2.3 7-1.1.2.3.1.2.1 8-1.1.2.1.1 10-1.1.2.1.1 14-1.1.1 15-1.1 18-1.1.3 19-1.1.3.1 20-1.1.3.1.2.r 21-1.1.3.1.2.1.1 23-1.1.2.1.1 23-1.1.3.1.2.1.1 25-1 25-1.1.2.3 27-1.2.2 28-1.2.2.1.1 29-1.2.2.1 30-1.2 32-1.1.3.1.2.1.1 34-1.1.2.1.1 34-1.1.3.1.2.1.1 35-1.2.1.1 36-1.2.1 38-1.4.1 40-1.4.1.1
Not unexpectedly , for all of the oncogenic B @-@ Raf proteins , the S729A mutation , which disrupts heterodimerization with C @-@ Raf , caused a > 90 % decrease in C @-@ Raf activity levels ( Fig . 5B ) .
SDL-AMR-09
JM domain
PI3K
--
2+
N-terminus
B-Raf
Cancer
cancer
IL-2
Eagle
p
p
1128
HER3
t
interleukin-6
EGFR
p3
SDL-AMR-09
One of the most abundantly expressed PSPs , protein phosphatase 2A ( PP2A ) , can regulate the Raf / Mek / Erk pathway both positively and negatively .
bio-kappa_0001.10
3-1.1.1.2.2.1.2.1.1 4-1.1.1.2.2.1.2.1 5-1.1.1.2.2.1.2 8-1.1.1.2.1.1 9-1.1.1.2.1.2 10-1.1.1.2.1.3 15-1 18-1.1.1.1.1.1 20-1.1.1.1.1.1 22-1.1.1.1.1.1 23-1.1.1.1 26-1.1
5C
1B
0-1 2-1.1.1.1 5-1.1.1.2.1.1.1 6-1.1.1 6-1.1.1.2 6-1.1.1.2.r 7-1.1 8-1.1.2.2 9-1.1.2 10-1.1.2.1.r 11-1.1.2.1.1.1.1 12-1.1.2.1 13-1.1.2.1.2.1.1 14-1.1.2.2.1.r 19-1.1.2.2.1.1 20-1.1.2.2.1 21-1.1.2.2.2 24-1.1.2.2.2.1 27-1.1.2.2.2.1.1
SDL-AMR-09
However , both of the CD72 transfectants showed reduced phosphorylation of ERK1 and ERK2 compared to that of the parent cells regardless of the duration of Ag stimulation .
bel_pmid_1064_0734.39810
10640734
1997
Furthermore , Erk @-@ 2 phosphorylated threonine 1179 and serine 1185 ( and to a lesser extent , serine 395 ) in vitro , suggesting the importance of this pathway for SRC @-@ 1 regulation .
SDL-AMR-09
bel_pmid_1066_0621.21334
10660621
0-1 2-1.1.2.1.1 4-1.1.2.1.1 5-1.1 6-1.1.1.1.2.1 7-1.1.1.1.1 8-1.1.1 9-1.1.1.2.2.1 9-1.1.1.3.2.1 10-1.1.1.2.1 13-1.1.1.r 15-1.1.1.3.3.1 15-1.1.1.3.3.1.1 15-1.1.1.3.3.1.1.r 16-1.1.1.3.3 18-1.1.1.3.2.1 19-1.1.1.3.1 21-1.1.3 22-1.1.3 24-1.1.4 26-1.1.4.1 27-1.1.4.1.1.r 28-1.1.4.1.1.1 29-1.1.4.1.1 30-1.1.4.1.2.r 31-1.1.4.1.2.1.1.1 33-1.1.4.1.2.1.1.1 34-1.1.4.1.2
Serial deletions identified a minimal HER3 promoter retaining transcriptional response to vemurafenib and AZD6244 , which was located between -@ 401 and -@ 42 bp ( Fig. 5C ) .
0-1.1.1 1-1.1 2-1 4-1.2.2 5-1.2.1.1.1.1 6-1.2 6-1.2.1 6-1.2.1.r 7-1.2.3 8-1.2.3.2 9-1.2.3.1 9-1.2.3.1.1 9-1.2.3.1.1.r 10-1.2.3.1.1.1.r 11-1.2.3.1.1.1.1.1.1 12-1.2.3.1.1.1 13-1.2.3.1.1.1.2.1.1 17-1.2.4.r 18-1.2.4 20-1.2.4.1.1 23-1.2.4.2.1 26-1.3.1 27-1.3.1.1
SDL-AMR-09
bio-exp_0001.7
pmid_1528_0923.1
15280923
0-1.2.2 1-1.2 2-1.2.1.r 3-1.2.1.1.1.1.1 4-1.2.1.1 5-1.2.1.1.2.1.1 7-1.2.1.1.2.1.1 8-1.2.1 9-1 10-1.1.1 11-1.1 12-1.1.1.1.r 13-1.1.1.1.1.2.1 14-1.1.1.1.1.2.2 15-1.1.1.1
Dual blockade of EGFR and ERK1 @/@ 2 phosphorylation potentiates growth inhibition of breast cancer cells ( PMID : 15280923 )
SDL-AMR-09
HER3
5B
Although phosphorylation of the S151 site appears to have the greatest effect on Ras binding , our results indicate that phosphorylation of all the feedback sites contributes to the inhibition of C @-@ Raf binding .
SDL-AMR-09
0-1.3.r 1-1.2.1 5-1.2.1.1 6-1.3 10-1.3.1.3 10-1.3.1.3.1 10-1.3.1.3.1.r 11-1.3.1 12-1.3.1.2.r 13-1.3.1.2.1.1.1 14-1.3.1.2 16-1.1.2 16-1.1.2.r 17-1.1 17-1.1.1 17-1.1.1.r 18-1 20-1.2.1 20-1.3.1.1 22-1.2.1.1.1 24-1.2.1.1.2 25-1.2.1.1 26-1.2 27-1.2.2.r 29-1.2.2 30-1.2.2.1.r 31-1.2.2.1.1.1.1 33-1.2.2.1.1.1.1 34-1.2.2.1
bio.mskcc_0001.54
1-1.1 2-1 3-1.2.r 4-1.2.1 4-1.2.1.1 4-1.2.1.1.r 5-1.2 6-1.2.2.2.1.1.1 8-1.2.2.2 9-1.2.2.1.1.1 10-1.2.2
The analysis revealed that monoubiquitination abrogates GAP @-@ mediated GTP hydrolysis .
SDL-AMR-09
bio.bmtr_0004.24
PKI166
PKC
CHO
transforming growth factor-b2
Activation of tyrosine kinases Fyn and Lyn , but not Lck , also occurred within 2 min after PAF stimulation in the cells
10729607
SDL-AMR-09
bel_pmid_1072_9607.19486
0-1.1 0-1.2 1-1.1.1.r 2-1.1.1.1.1.1 2-1.1.1.2.1.1 3-1.1.1.1.1.2 3-1.1.1.2.1.2 4-1.1.1.1.1.3 5-1.1.1 6-1.1.1.2.1.3 8-1 9-1.2.1 9-1.2.1.r 10-1.2.2.1.1 12-1.1.3 14-1.1.2 14-1.1.2.2 14-1.1.2.2.1.1.r 14-1.1.2.2.r 15-1.1.2.2.1.1 16-1.1.2.2.1.2 17-1.1.2 18-1.1.2.1.1.1.1 19-1.1.2.1 20-1.1.2.1.2.r 22-1.1.2.1.2
B-Raf
-
JAK1
G12V
d2
NRX IV
0-1.1 1-1 2-1.2.1.1.1 3-1.2 3-1.3 6-1.3.1.r 7-1.3.1.1.1 8-1.3.1.1.2 12-1.3.2 13-1.3.2.1.r 14-1.3.2.1.1.1.1.1 15-1.3.2.1 16-1.3.2.1.2.1.1.1 17-1.3.2.1.1.1 17-1.3.2.1.2.1 18-1.3.2.1.1 18-1.3.2.1.2 20-1.4.1.1.1.1 22-1.4.1.1.1.2 24-1.4.1.1.1.3
bio.chicago_2015.18776
SDL-AMR-09
We compared cdc25A induction to that of cyclin E , which is regulated by E2F and Rb family members ( 4 , 20 , 45 ) .
bmtr_0007.12
SDL-AMR-09
All these demonstrate that ASPP2 is a novel substrate of MAPK and Ser827 of ASPP2 can be phosphorylated by RAS @/@ MAPK pathway .
0-1.1.1 1-1.1 2-1 4-1.2.1.2.1.1 7-1.2.1.3 10-1.2.1.1.1.1 14-1.2.1.2.1.1 15-1.2.2 17-1.2.2.1 18-1.2.2.1.2.r 19-1.2.2.1.2.1.1 21-1.2.2.1.2.1.1 22-1.2.2.1.2
tyrosine
tyrosine kinase receptor
HEK293T
Axin
e
147
B-Raf
bmtr_0006.4
SDL-AMR-09
This state is considered to be a short @-@ lived transition state intermediate in vivo [ 36 ] based on the relatively high GTP : GDP ratio in vivo [ 37 ] , the ability of GTP to dissociate the GEF @-@ Ras complex in vitro [ 31 ] , and the assumption that there are no proteins in vivo that might stabilize nucleotide @-@ free Ras and prevent GTP loading .
0-1.1.6 1-1.1 3-1 7-1.1.2.1 9-1.1.2 10-1.1.1 11-1.1 12-1.1.3 13-1.1.3.1 14-1.1.3.1 16-1.1.5.1.1.1 18-1.1.4 19-1.1.4.1.r 21-1.1.4.1.1.4.1 22-1.1.4.1.1.4 23-1.1.4.1.1.1.1.1 25-1.1.4.1.1.2.2.1 26-1.1.4.1.1 27-1.1.3.1 28-1.1.3.1 30-1.1.4.1.1.5.1.1.1 34-1.1.4.1.2 35-1.1.4.1.1 35-1.1.4.1.2.2.r 36-1.1.4.1.2.2.1 38-1.1.4.1.2.2 40-1.1.4.1.2.2.2.1.1.1 42-1.1.4.1.2.2.2.2.1.1 43-1.1.4.1.2.2.2 44-1.1.4.1.2.2.3 45-1.1.4.1.2.2.3 47-1.1.4.1.2.3.1.1.1 50-1.1.4.1 52-1.1.4.1.3 56-1.1.4.1.3.1.1 56-1.1.4.1.3.1.1.r 57-1.1.4.1.3.1 58-1.1.4.1.3.1.2 59-1.1.4.1.3.1.2 61-1.1.4.1.3.1.3.2 62-1.1.4.1.3.1.3 63-1.1.4.1.3.1.3.1.2.1 65-1.1.4.1.3.1.3.1 65-1.1.4.1.3.1.3.1.2 65-1.1.4.1.3.1.3.1.2.r 66-1.1.4.1.3.1.3.1.1.1 68-1.1.4.1.3.1.4 69-1.1.4.1.3.1.4.1.1 70-1.1.4.1.3.1.4.1
tyrosine
EGFR
2-1.1.2 3-1.1.1.1 5-1.1.1.1 7-1.2 7-1.2.r 8-1 9-1.3.r 10-1.3.1 12-1.3.1.1.1.1 13-1.3
His @-@ ubiquitinated K @-@ Ras was subsequently purified with anti @-@ Flag resin .
SDL-AMR-09
bio.bmtr_0001.5
TGF-beta
B-Raf
K-Ras
p53
SDL-AMR-09
bio.mskcc_0001.11
The Pin1 prolyl @-@ isomerase binds specifically to phosphorylated S/TP ( pS/TP ) motifs ( 33 ) , and isomerization of the pS @/@ TP bond is required for PP2A to efficiently dephosphorylate certain proteins , such as cdc25C , Myc , and C @-@ Raf ( 16 ) .
1-1.1.1.1.1 2-1.1.1 4-1.1.1 5-1.1 6-1.1.3 7-1.1.2.r 8-1.1.2.1 13-1.1.2 15-1.1.4.1.1.1 18-1 19-1.2.2 23-1.2.2.1.1 25-1.2.2.1 27-1.2 28-1.2.1.r 29-1.2.1.2.1.1 31-1.2.1.3 32-1.2.1 33-1.2.1.1.2 34-1.2.1.1 36-1.2.1.1.1.r 37-1.2.1.1.1.r 38-1.2.1.1.1.1.1.1 40-1.2.1.1.1.2.1.1 42-1.2.1.1.1 43-1.2.1.1.1.3.1.1 45-1.2.1.1.1.3.1.1 47-1.2.3.1.1.1
RBW-1
SUM149
0-1 1-1 3-1.1.1 4-1.1 5-1.1.2.r 6-1.1.2.1.1.1 7-1.1.2 9-1.1.2.2 10-1.1.2.2.1.r 11-1.1.2.2.1.1.1 13-1.1.2.2.1.1.1 14-1.1.2.2.2.r 15-1.1.2.2.2.1.1 17-1.1.2.2.2.1.1
In addition , we found that Rheb inhibits the association of B @-@ Raf with H @-@ Ras .
SDL-AMR-09
bio.bel_0002.10
GTP
bio.bel_0002.1
0-1.1.2.2.1.1.1 1-1.1.2.2.1.1.2 2-1.1.2.2.1.1.3 4-1.1.2.2 5-1.1.2 6-1.1.2.1.r 7-1.1.2.1.2.1 8-1.1.2.1.1 11-1.1.2.1.3.1 12-1.1.2.1.3 13-1.1.2.1.3.2.r 14-1.1.2.1.3.2.1.1 16-1.1.2.1.3.2.1.1 17-1.1.3 18-1.1 19-1.1.1.1 19-1.1.1.1.r 20-1.1.1 21-1.1.1.2.r 22-1.1.1.2.1.1 23-1 24-1.2 26-1.2.2 27-1.2.2.2.r 28-1.2.2.2.1.1 30-1.2.2.2.1.1
Protein kinase A @-@ dependent phosphorylation of serine 43 within the regulatory domain of Raf @-@ 1 reciprocally potentiates its interaction with Rheb and decreases its interaction with H @-@ Ras .
SDL-AMR-09
PAF receptor
401
threonine
Chk2
SDL-AMR-09
bel_pmid_1074_4722.21170
As shown in the Western blot ( Fig . 1A , lane 3 ) , the phospho @-@ S216 antibody recognized Cdc25C that was incubated with a wild type Chk2 in the in vitro kinase assay but failed to recognize unphosphorylated Cdc25C , incubated with a kinase @-@ dead mutant ( D347A ) ( Fig . 1A , lane 2 ) .
0-1.1.2.2.2.r 1-1.3 2-1.1.2.2.2.2 2-1.3.1.r 4-1.3.1 5-1.3.1 7-1.3.1.1.1.1 9-1.3.1.1.1.1.1 11-1.3.1.1.1.2 12-1.3.1.1.1.2.1 16-1.2.2.2.2 19-1.1.1 20-1.1 21-1.1.2.1.1 24-1.1.2.2 25-1.1.2.2.1.r 27-1.1.2.2.1.2 28-1.1.2.2.1.2 29-1.1.2.2.1.1.1 30-1.1.2.2.2.2 32-1.1.2.2.2.2 33-1.1.2.2.2.2 34-1.1.2.2.2.1 35-1.1.2.2.2 36-1 37-1.2 39-1.2.2 41-1.2.2.2.1.1 43-1.2.2.2.3 44-1.2.2.2.3.1.r 46-1.2.2.2.3.1.2.2 49-1.2.2.2.3.1 49-1.2.2.2.3.1.1 49-1.2.2.2.3.1.1.r 51-1.2.2.2.3.1.1.1 54-1.2.3.1.1 56-1.2.3.1.1.1 58-1.2.3.1.2 59-1.2.3.1.2.1
10744722
0-1.1 1-1.1.1.r 2-1.1.1.1.1 3-1.3 4-1 5-1.2 6-1.2.1.r 8-1.2.1.3.1.1.1 10-1.2.1.3.1.1.1 11-1.2.1.4 12-1.2.1.3 16-1.2.1.1.1.1 16-1.2.1.2.1.1 17-1.2.1 21-1.2.1.1.1.1 21-1.2.1.2.1.1
a_pmid_2488_5690.13
Treatment with dabrafenib efficiently inhibited phosphorylation of the B @-@ Raf downstream targets Mek 1 @/@ 2 and Erk 1 @/@ 2 .
24885690
SDL-AMR-09
SDL-AMR-09
0-1.1.1.1 2-1.1.1.1.2.1.1 2-1.2.1.2.1 3-1.2.1.1 4-1.1.1.1.1.r 5-1.1.1.1.1.1.1 6-1.1.1.1.3.r 6-1.1.1.2.3 8-1.1.1.1.3.2.2.1.1 10-1.1.1.1.3.2.2.1 11-1.1.1.1.3.2.2 14-1.1.1.1.3.1.1 14-1.1.1.2.1.1.1.1 15-1.1.1.3 16-1.1.1 17-1.1 19-1.1.2.1 20-1.1.2 22-1.1.2.2 23-1.1.2.2 24-1.1.2.2 25-1.1.2.2 26-1.1.2.2 27-1.1.2.2 28-1.1.2.2 29-1.1.2.2 31-1.1.3.1 33-1.1.3.1.1 35-1.2.1.2.1 36-1.2.1.1 37-1.2 39-1.2.1.3.2 40-1.2.1.3.2.1.1 41-1.2.1.3.2.1 44-1.2.1.3.1 45-1.2.1.3.1.1
Substitution of threonine 68 by alanine in the full @-@ length kinase @-@ dead Chk2 dramatically reduced but did not abolish the ATM phosphorylation of Chk2 @/@ Cds1 in vitro ( Fig . 4B ; threonine 68 accounts for approximately 70 % of the total phosphorylation ) .
10744722
bel_pmid_1074_4722.21126
Histone 2B
GDP
Guanosine_diphosphate
HA-MEKK1-K1255M
u
5D
p2
-
−−
B-Raf
Ras
e3
carboxy-terminus
l2
GAP
0-1 2-1.1 4-1.1.1.2.1.1 6-1.1.1.2.1.1 8-1.1.1.2.1.1 9-1.1.1.2 10-1.1.1.2 11-1.1.1.2.2.r 12-1.1.1.2.2.2.1 13-1.1.1.2.2.2 14-1.1.1.2.2.1.1 16-1.1.1.2.2.1.1 17-1.1.1 19-1.1.1.1.2.1 20-1.1.1.1.2 21-1.1.1.1 22-1.1.1.1.1.r 23-1.1.1.1.1.1.1 25-1.1.2.1 26-1.1.2
SDL-AMR-09
pmid_1528_0923.76
15280923
Thus , while the MDA @-@ MB @-@ 231 cell line with highly activated ERK1 @/@ 2 expressed a relatively high level of EGFR , other combinations occur .
His - tagged ubiquitin and Flag - tagged K @-@ Ras4B ( K @-@ Ras hereafter ) were expressed in HEK293T cells at levels similar to endogenous K @-@ Ras ( Fig. 1B ) and subjected to sequential affinity chromatography .
bio.ras_0003.2
2-1.1.1.1.2 2-1.1.1.2.3 3-1.1.1.1.1.1 5-1.1.1.2.3.1.1.1 7-1.1.1.2.3 8-1.1.1.2.1.1 8-1.1.1.2.2.1 10-1.1.1.2.1.1 12-1.1.1.2.1.1 12-1.1.1.2.2.1 14-1.1.1.2.2.1 18-1.1 18-1.1.3.1.1.1 19-1.1.2.r 20-1.1.2.1.1 21-1.1.2 22-1.1.3.r 23-1.1.3 23-1.1.3.1.1 24-1.1.3.1 25-1.1.3.1.1.1.1.r 26-1.1.3.1.1.1.1.2 27-1.1.1.2.1.1 27-1.1.1.2.2.1 27-1.1.3.1.1.1.1.1.1 29-1.1.1.2.2.1 29-1.1.3.1.1.1.1.1.1 31-1.1.4.1 32-1.1.4.1.1 34-1 35-1.2 36-1.2.2.r 37-1.2.2.2 38-1.2.2.1 39-1.2.2
SDL-AMR-09
C-Raf
bio.bmtr_0002.4
SDL-AMR-09
Targeting both the phosphorylated and non @-@ phosphorylated peptide forms , we detected a 66 % average decrease in EGFR T669 phosphorylation and a 75 % decrease in HER2 T677 phosphorylation upon treatment with AZD6244 ( Figure 5B , Supplemental Figure 8 ) .
0-1.3 3-1.3.2.2.1 5-1.3.2.2.1.1 5-1.3.2.2.1.1.r 7-1.3.2.1.1 7-1.3.2.2.1 8-1.3.2.1 8-1.3.2.2 11-1.1 12-1 14-1.2.1.2.1 15-1.2.1.2 16-1.2.1.2.2 17-1.2.1 18-1.2.1.1.r 19-1.2.1.1.1.3.1.1 21-1.2.1.1 22-1.2 24-1.2.2.2.1 25-1.2.2.2 26-1.2.2 27-1.2.2.1.r 28-1.2.2.1.1.3.1.1 30-1.2.2.1 32-1.4 33-1.4.1.r 34-1.4.1.1.1 36-1.5.1.1 37-1.5.1.1.1 39-1.5.1.2.2 40-1.5.1.2 41-1.5.1.2.1
CHO-KI
5A
pmid_1528_0923.95
MDA @-@ MB @-@ 435 cells were significantly inhibited by U0126 alone , and the addition of PKI166 made no difference .
0-1.1.2.1.1 2-1.1.2.1.1 4-1.1.2.1.1 5-1.1.2 7-1.1.3 8-1.1 9-1.1.1.r 10-1.1.1.1.1 11-1.1.1.2 13-1 15-1.2.2 16-1.2.2.1.r 17-1.2.2.1.1.1 18-1.2 19-1.2.1 19-1.2.1.r 20-1.2.1.r 20-1.2.3
15280923
SDL-AMR-09
protein phosphatase 2A
0-1.1.1.1 0-1.2 1-1.1.1 3-1 5-1.1.2.1 6-1.1.2 7-1.1 9-1.2.1 10-1.2.1 11-1.2.1.1.1 12-1.2.1.1 14-1.2 16-1.3.1.1 16-1.3.1.2 25-1.4 26-1.4.1.r 27-1.4.1.2.1 28-1.4.1.2.1.1 29-1.4.1 29-1.4.1.1 29-1.4.1.1.r 30-1.4.1.2 32-1.4.1.2.2.2 33-1.4.1.2.2 34-1.4.1.2.2.1.r 35-1.4.1.2.2.1.1 36-1.4.1.2.2.1 37-1.4.1.2.2.3 39-1.4.1.2.2.3.1 40-1.4.1.2.2.3.1.1.r 41-1.4.1.2.2.3.1.1
SDL-AMR-09
24885690
Cellular senescence was detected at very low levels in less than 5 % of cells ( Figure <xref ref-type="fig" rid="F2"> 2 </xref>@ D @-@ E ) , indicating that senescence alone cannot explain the strong reduction in cell growth observed upon withdrawal of serum .
a_pmid_2488_5690.58
1-2
s
e
OPCA
carcinoma
SDL-AMR-09
The effects of the MEK inhibitor on total HER2 , HER3 protein and on pHER3 were dose dependent , and inversely associated with the degree of inhibition of pERK ( Fig. 5B ) .
bio-exp_0001.5
1-1.1.1 2-1.1.1.1.r 4-1.1.1.1.1.1.1.1 5-1.1.1.1 5-1.1.1.1.1 5-1.1.1.1.1.r 6-1.1.1.2.r 7-1.1.1.2.1.2 8-1.1.1.2.1.1.1 10-1.1.1.2.2.1.1 10-1.1.1.2.3.1.1 11-1.1.1.1.1.1 16-1.1.2 17-1.1 19-1 20-1.2.3 20-1.2.3.r 21-1.2 22-1.2.2.r 24-1.2.2.1.r 26-1.2.2.1 28-1.1.1.2.3.2 28-1.2.2.1.1.1.1 30-1.3.1 31-1.3.1.1
Lck
Under standard long @-@ term cell culture conditions no differences in morphology or growth were observed between the cell clones ( Figures <xref ref-type="fig" rid="F1"> 1 </xref>@ B and <xref ref-type="fig" rid="F2"> 2 </xref>@ A ) .
1-1.2.1 2-1.2.2.2 5-1.2.2.1 6-1.2.2 7-1.2 7-1.2.r 8-1.1.1 8-1.1.1.r 9-1.1 10-1.1.3.r 11-1.1.3.1 12-1.1.3 13-1.1.3.2 15-1 18-1.1.2 19-1.1.2.1 21-1.3.1.1 21-1.3.1.2 26-1.3.1
a_pmid_2488_5690.49
SDL-AMR-09
24885690
SDL-AMR-09
bio.chicago_2015.17177
We now report that , although PS1 mutations augment gamma @-@ secretase cleavage at residue 42 , they in fact suppress both S3 @-@ cleavage of Notch and epsilon @-@ cleavage of APP near residue 50 .
0-1.1 1-1.3 2-1 5-1.2.4.r 6-1.2.4.1.1.1.1 7-1.2.4.1 8-1.2.4 9-1.2.4.2.1.1.2.1.1 11-1.2.4.2.1.1.2.1.1 12-1.2.4.2 14-1.2.4.2.1 15-1.2.4.2.1.1.1 17-1.2.1 18-1.2.3 19-1.2.3 20-1.2 22-1.2.2.1.1.1.1 24-1.2.2.1 26-1.2.2.1.1.2.1.1 27-1.2.2 28-1.2.2.2.1.1.1 30-1.2.2.2 32-1.2.2.2.1.2.1.1 33-1.2.2.1.1 33-1.2.2.1.1.3 33-1.2.2.1.1.3.r 34-1.2.2.1.1.3.1 35-1.2.2.1.1.3.1.1.1
K-Ras
GTP
C-Raf
bio.ras_0001.5
SDL-AMR-09
1-1.2 2-1.2.r 7-1.1.1.1.1.1 8-1.1.1 9-1.1.1.2.1.1 10-1.1 11-1.1.2.r 13-1.1.2.1.1 15-1.1.2.1.1 17-1
Under physiological conditions , the rate of GDP or GTP release from the G - domain is slow .
1-1.3 2-1.3.1.3.1 2-1.3.1.3.1.r 4-1.3.1.3.2.1.1 6-1.3.1.3.2.1.1 7-1.3.1.3 8-1.3.1.3.r 9-1.3.1.2 11-1.3.1.1.1 12-1.3.1.1 13-1.3.1 15-1.1.1.1 16-1.1.1 17-1.1.1 19-1.1 25-1.1.2.2.1 26-1.1.2.2 28-1 29-1.2.1.1 30-1.2.1 32-1.2 33-1.1.2.1.r 33-1.2.2.r 35-1.2.2
SDL-AMR-09
15280923
pmid_1528_0923.69
To test whether the ERK1 @/@ 2 activity was only a tissue culture phenomenon , selected cell lines were injected into the mammary fatpads of nude mice , and protein lysates were prepared from the tumours .
3
p2
2-1.3 4-1 4-1.4 4-1.4.r 5-1.2.r 6-1.2 7-1.2 8-1.2.2.2 9-1.2.2 10-1.2.2.1.r 12-1.2.2.1.1.1.1.1 13-1.2.2.1 13-1.2.2.1.1 13-1.2.2.1.1.r 14-1.2.3.r 15-1.2.3.1.2 16-1.2.3.1.1.1 17-1.2.3 18-1.2.3 20-1.4.1.1.1
SDL-AMR-09
CtBPs have also been described to negatively regulate transcriptional activity of the HER3 promoter in breast carcinoma cell lines ( 30 ) .
bio.bmtr_0003.12
DLT
cancer
Cancer
ERK12
calcium
B-Raf
Dpp
U0126
0-1.1 0-1.3.1.3.1.1.1 2-1.1.1.r 3-1.1.1.3.2 4-1.1.1.3 5-1.1.1.3.1.r 6-1.1.1.3.1 8-1.1.1.1.1 9-1.1.1.1 10-1.1.1 11-1.1.1.2.2 12-1.1.1.2 13-1.1.1.1.2.1.1.1 15-1.1.1.1.2.1.1.1 16-1.1.1.1.2 18-1.1.2.1 18-1.2.2.1 19-1.1.2.1.1 19-1.2.2.1.1 23-1.2.3 25-1.2.1.1.1.2.1 29-1.2.1.1 30-1.2.1.1.3.1 31-1.2.1.1.3 33-1.2.1.1.4 35-1.2 37-1.2.1 38-1.2.1.2 39-1.2.1.2.1.r 40-1.2.1.2.1.1.1 42-1.1.2.1 42-1.2.2.1 43-1.1.2.1.1 43-1.2.2.1.1 48-1.3.1.1.1 48-1.3.1.1.1.1.1 48-1.3.1.1.1.1.2 49-1.3.1.1.1.1 51-1.3.1.1.1.1.r 52-1.3.1.1.1.1.r 53-1.3.1.1.1.1.1.1.1 55-1.3.1.1.1.1.2.1.1 57-1.3.1.1.2.1.1.1.1 59-1.3.1.1.2.1.1.1.1 61-1.3.1.1.2.1.2.1.1 63-1.3.1.1.2.1 64-1.3.1.1.2.1.3.1.1 65-1.3.1 66-1.3.1.2.1.1.1.1 68-1.3.1.2.1.1.1.1 69-1.3.1.2.1 70-1.3.1.2 71-1.3.1.2.2
Furthermore , in many types of cells , antioxidants diminish or completely eliminate NF @-@ kB activation ( Table 1 ) . For example , H2O2 , UV , and ionizing radiation have all been observed to stimulate degradation of IkB ( Table 1 ) . Conversely , antioxidants and reductants such as BHA , NGA , a @-@ tocopherol , NAC , and PDTC decrease NF @-@ kB activity and translocation [ 12,253 ] .
SDL-AMR-09
10699758
bel_pmid_1069_9758.34686
H-Ras
PKI166
The total number of foci observed and , often , the sizes of the foci were increased , and cells within the foci exhibited a more transformed appearance .
SDL-AMR-09
bio.mskcc_0001.33
1-1.1.1.1.1 2-1.1.1.1 3-1.1.1.1.1.1.r 4-1.1.1.1.1.1 5-1.1.1.1.1.1.1 6-1.1.1 8-1.1.2 11-1.1.1.2 12-1.1.1.2.1.r 14-1.1.1.2.1 16-1.1 18-1 18-1.1.1 19-1.2.1 22-1.2.1.1 23-1.2 25-1.2.2.2.1 26-1.2.2.2 27-1.2.2
p
SDL-AMR-09
bio.bmtr_0004.25
All other activities , including the ability to bind regulators , were largely preserved and our kinetic modeling suggests that the GAP defect will dominate .
0-1.1.1.1 1-1.1.1.2 2-1.1.1 4-1.1.1.3 8-1.1.1.3.1.1 9-1.1.1.3.1.1.1 9-1.1.1.3.1.1.1.1 9-1.1.1.3.1.1.1.1.r 12-1.1.2 13-1.1 14-1 15-1.2.1.1 15-1.2.1.1.r 16-1.2.1.2 17-1.2.1 18-1.2 19-1.2.2.r 21-1.2.2.1.1.1.1 22-1.2.2.1 24-1.2.2
neurotransmitter transporter
SDL-AMR-09
bio.bel_0002.8
disruption of the KSR1 @/@ CK2 interaction or inhibition of CK2 activity significantly reduces the growth @-@ factor @-@ induced phosphorylation of C @-@ Raf and B @-@ Raf on the activating serine site in the negative @-@ charge regulatory region ( N @-@ region ) .
0-1.1.1 1-1.1.1.1.r 3-1.1.1.1.1.1.1 5-1.1.1.1.2.1.1 6-1.1.1.1 7-1.1 8-1.1.2 9-1.1.2.1.r 10-1.1.2.1.1 11-1.1.2.1 12-1.3 13-1 15-1.2.2.1 17-1.2.2.1 19-1.2.2 20-1.2 21-1.2.1.r 22-1.2.1.3.3.1.1.1 24-1.2.1.3.3.1.1.1 24-1.2.1.3.3.2.1.1 25-1.2.1.3.3 26-1.2.1.3.3.2.1.1 28-1.2.1.3.3.1.1.1 28-1.2.1.3.3.2.1.1 31-1.2.1.1 32-1.2.1.2.1.1 33-1.2.1 36-1.2.1.3.2.1 38-1.2.1.3.2 39-1.2.1.3.1 40-1.2.1.3 44-1.2.1.3
-
s2
Ras , like all GTPases , cycles between an inactive GDP @-@ bound state and an active GTP @-@ bound state .
SDL-AMR-09
0-1.1.1.1 0-1.2.1.1 0-1.3.1.1 3-1.1.2.1.2 6-1 9-1.2 9-1.2.2 9-1.2.2.1 9-1.2.2.1.r 9-1.2.2.r 9-1.3 9-1.3.2 9-1.3.2.r 10-1.2.3.1.1.1 12-1.2.3 12-1.3.3 16-1.2 16-1.2.2 16-1.2.2.r 16-1.3 16-1.3.2 16-1.3.2.r 17-1.3.3.1.1.1 19-1.2.3 19-1.3.3
bmtr_0006.2
26
pmid_1528_0923.92
Inhibition of growth by PKI166 was most effective in cells with high levels of EGFR and nonactivated ERK1 @/@ 2 ( SUM149 , MDA @-@ MB @-@ 468 ) when compared with cells with high EGFR and high basal level of phosphorylated ERK1 @/@ 2 ( MDA @-@ MB @-@ 231 ) .
0-1.1 1-1.1.2.r 2-1.1.2 3-1.1.1.r 4-1.1.1.1.1 6-1.2 7-1 9-1.3 9-1.4 11-1.4.1.1.1.1 12-1.3.1.1 12-1.4.1.1.1 13-1.3.1.1.2.r 14-1.3.1.1.2.1.1.1 15-1.3.1.1.2 17-1.3.1.1.2.2.1.1 19-1.3.1.1.2.2.1.1 21-1.3.2.1.1.1.1 23-1.3.2.1.2.1.1 25-1.3.2.1.2.1.1 27-1.3.2.1.2.1.1 30-1.4.r 32-1.3.2.1.1 32-1.3.2.1.2 32-1.4.2.1 33-1.3.1.1.1.r 34-1.3.1.1.1 35-1.3.1.1.2.1.1.1 36-1.3.2.1 37-1.4.1.1.2.3 38-1.4.1.1.2.1 39-1.4.1.1.2 40-1.4.1.1.2.2.r 41-1.4.1.1.2.2.2 42-1.4.1.1.2.2.1.1 44-1.4.1.1.2.2.1.1 46-1.4.2.1.1.1 48-1.4.2.1.1.1 50-1.4.2.1.1.1
SDL-AMR-09
15280923
IGF-IR
B-Raf
729
serine
bio.bmtr_0005.14
SDL-AMR-09
Each eluted fraction was measured for its radioactivity content ( Figure 1B , right panel ) .
0-1.1.2 1-1.1.1 2-1.1 4-1 7-1.2.1 8-1.2 8-1.2.2 8-1.2.2.r 10-1.3.1.2 11-1.3.1.2.1 13-1.3.1.1 14-1.3.1
0-1.1.2 1-1.1.2 2-1.1.1.1 4-1.1.1 5-1.1 6-1 7-1.2.r 8-1.2.1.1 9-1.2.1 12-1.2.2 13-1.2 14-1.1.2 14-1.2.3.r 15-1.2.3 16-1.2.3.1.r 17-1.2.3.1.2.1 19-1.2.3.1.2.2 20-1.2.3.1 21-1.2.3.1.1.r 22-1.2.3.1.1.2.2 23-1.2.3.1.1.2.1.1 25-1.2.3.1.1.2.1.1 26-1.2.3.1.1.1.1 30-1.2.3.1.1.4.1 32-1.1.2 33-1.2.4.r 35-1.2.4.1 35-1.2.4.2 36-1.2.4.1.1.1 37-1.2.4.2.1 41-1.2.4.1.3.1 42-1.2.3.1.1.4 42-1.2.4.1.3 46-1.2.4.1.2.1 48-1.2.4.1.1.2 48-1.2.4.2.1.2 49-1.2.4.1.1.2.1 50-1.2.4.1.1.2.1.1 52-1.2.4 53-1.2.4.1.1 55-1.2.1.2.1 55-1.2.4.2.1.1.2.1.1 55-1.2.4.2.1.1.2.1.1.r 57-1.2.4.2.1.1.2.1 58-1.2.4.2.1.1.2 59-1.2.4.2.1.1.1.1 63-1.2.4.2.1.1.3.1 64-1.2.4.2.1.1.3 68-1.2.4.2.1.1.4.1 70-1.2.4.1.1.2 71-1.2.4.1.1.2.1 72-1.2.4.1.1.2.1.1 76-1.2.4.3.1 77-1.2.3.1.2 77-1.2.4.3 77-1.2.4.3.r
bel_pmid_1079_1191.20850
In situ end @-@ labeling detection showed that apoptotic cell death was significantly increased in cells with 5 @-@ day treatment of antisense H @-@ ras oligodeoxynucleotide ( 34.0 +/- 4.5 %) in comparing with cells without treatment ( 2.5 +/- 1.2 % , t = 13.434 , P < 0.01 ) or treated with non @-@ specific antisense oligodeoxynucleotide ( 4.8 +/- 1.4 % , t = 12.453 , P < 0.01 ) at the corresponding time .
10791191
SDL-AMR-09
ERK12
beta-catenin
C-terminus
e
interrogative
s
p3
0-1.1.1 1-1.1 2-1 3-1.2.r 5-1.2.1.1.1.1.1 7-1.2.1.1.1.1 9-1.2.1.1 10-1.2 11-1.2.1 12-1.2.1.2.2.1.1 13-1.2.1.2 14-1.2.1.2.1.r 15-1.2.1.2.1.1.1 16-1.2.1.2.1.1.2 17-1.2.1.2.3.r 19-1.2.1.2.3.1.1.1 20-1.2.1.2.3
This observation suggested that the 60 @-@ residue linker region may assist Ldb binding by LIM B in the 1m construct .
bio.chicago_2015.18031
SDL-AMR-09
0.1
HER2
ERK
SDL-AMR-09
bio.bmtr_0005.4
0-1.3 1-1.1.1.1.1 2-1.1 3-1.1.2.1.1 4-1 5-1.2.1.1.1 7-1.2.2.1.1 8-1.1 9-1.4 10-1.4.1.1 11-1.4.1 13-1.4.2 14-1.4.2.2.1.1.1.1 15-1.4.2.2.1 16-1.4.2.2 18-1.5.1.1.1
Mechanistically ASPP1 and ASPP2 bind RAS @-@ GTP and potentiates RAS signalling to enhance p53 mediated apoptosis [ 2 ] .
93
cytokine
CRE
Shp2
Raf
PS1
22
bio.bmtr_0002.19
SDL-AMR-09
1-1.5 3-1.2 4-1.2.1.r 5-1.2.1.1.1 8-1.4 9-1 10-1.3.1.1.1.1 11-1.3.1 12-1.3.1.2.1.1 13-1.3 14-1.3.2.r 15-1.3.2 16-1.3.2.1 19-1.3.2.1.1 19-1.3.2.1.1.2 19-1.3.2.1.1.2.r
As expected , addition of AZD6244 failed to further augment ERBB3 and AKT phosphorylation in cells expressing the 669A mutant .
PKC betaII
S729A
-
SDL-AMR-09
0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 2-1 3-1.2 5-1.3 7-1.3.2 8-1.3.2.1.r 9-1.3.2.1 9-1.3.2.1.1 9-1.3.2.1.1.r 10-1.3.2.2.r 12-1.3.2.2 13-1.3.2.2.1.r 14-1.3.2.2.1.1.1 15-1.3.2.2.2.3.1.r 16-1.3.2.2.2.3.1 17-1.3.2.2.2.3 18-1.3.2.2.2.1.1.1 19-1.3.2.2.2 20-1.3.2.2.2.2.1.1 23-1.3.2.2.2.4.2 24-1.3.2.2.2.4 26-1.3.2.2.2.4.1.1 27-1.3.2.2.2.4.1
These results led us to examine the effect of monoubiquitination on the interaction of Ras with its cognate GEF and GAPs , which also target the switch domains .
bio.bmtr_0004.23
bio-kappa_0001.8
Phosphorylated Ksr can also function as a transactivator ; however , since Raf binding to Ksr induces limited kinase activity , in quiescent cells the constitutive association of Ksr with B @-@ Raf may serve to prevent C @-@ Raf binding to B @-@ Raf , safeguarding against undue activation of the pathway .
0-1.1.1.2 1-1.1.1.1.1 2-1.1.3 3-1.1.2 9-1.1.3.r 11-1.1.3.3 12-1.1.3.3.1.1.1.1.1 13-1.1.3.3.1.1 14-1.1.3.3 14-1.1.3.3.1.1.2.r 15-1.1.3.3.1.1.2 16-1.1.3.3.1 17-1.1.3.3.1.2.2 18-1.1.3.3.1.2.1 19-1.1.3.3.1.2 22-1.1.3.2.1 23-1.1.3.2 25-1.1.3.1.1.3 26-1.1.3.1.1 27-1.1.3.1.1.1.r 28-1.1.3.1.1.1 29-1.1.3.1.1.2.r 30-1.1.3.1.1.2.1.1 32-1.1.3.1.1.2.1.1 33-1 33-1.1.3 34-1.1.3.1 36-1.1.3.1.2 37-1.1.3.1.2.2.1.1.1 39-1.1.3.1.2.2.1.1.1 40-1.1.3.1.2.2 41-1.1.3.1.2.2.2.r 42-1.1.3.1.2.2.2 43-1.1.3.1.2.2.2 44-1.1.3.1.2.2.2 46-1.1.3.1.2.3 48-1.1.3.1.2.3.1.2 48-1.1.3.1.2.3.1.2.1 48-1.1.3.1.2.3.1.2.1.r 49-1.1.3.1.2.3.1 50-1.1.3.1.2.3.1.1.r 52-1.1.3.1.2.3.1.1
SDL-AMR-09
AKT
bio-kappa_0001.5
Allosteric activation by B @-@ Raf induces cis @-@ autophosporylation in the activation loop of the receiver kinase , i.e. C @-@ Raf , and renders it able to phosphorylate Mek .
SDL-AMR-09
0-1.1.1.2 1-1.1.1 2-1.1.1.1.r 3-1.1.1.1.1.1 5-1.1.1.1.1.1 6-1.1 12-1.1.2.3.1 13-1.1.2.3 17-1.1.2.3.1.1 20-1.1.2.3.1.1.2.1.1.1 22-1.1.1.1.1.1 22-1.1.2.3.1.1.2.1.1.1 24-1 25-1.2 26-1.2.1 27-1.2.2 29-1.1.2 29-1.2.2.1 30-1.2.2.1.1.1.1
20
lysine
1
bio.chicago_2015.18127
SDL-AMR-09
Axin also blocks beta @-@ catenin @-@ mediated transcription in colon cancer cells that have a mutation in the adenomatous polyposis coli gene .
0-1.1.1.1 1-1.4 2-1 3-1.2.1.1.1.1 5-1.2.1.1.1.1 7-1.2.1 8-1.2 9-1.3.r 10-1.3.2.2.1 11-1.3.2.2.2 12-1.3 16-1.3.3 17-1.3.3.1.r 19-1.3.3.1.1.1 20-1.3.3.1.1.2 21-1.3.3.1.1.3 22-1.3.3.1
Cds1
fibronectin
bio.bmtr_0005.13
1-1.1.2.2 2-1.1.2.1.1.1 4-1.1.2.2.1.r 5-1.1.2.2.1.1.1 7-1.1 8-1.1.1.r 9-1.1.1.1.1 10-1 11-1.2 12-1.2.2.r 14-1.2.2.1.1.1 15-1.2.2.1.1 16-1.2.2.1 17-1.2.2
The phosphorylated ASPP2 fragment by MAPK1 was digested by trypsin and fractioned on a high performance liquid chromatography ( HPLC ) .
SDL-AMR-09
bio-exp_0001.15
0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 3-1 4-1.2.r 6-1.2.1 6-1.2.1.1 6-1.2.1.1.r 7-1.2 8-1.2 10-1.3.1.2 11-1.3.1 12-1.3.1.1
These findings were confirmed in a second cell line ( Supplementary Fig. S5A ) .
SDL-AMR-09
3
DNA
DNA
6
BCR
C-Raf
-
47
456
IGF-IR
-1
Cancer
cancer
2B
24885690
0-1.1.1 2-1.1 3-1 4-1.2 5-1.2.1.r 6-1.2.1 6-1.2.1.2 6-1.2.1.2.r 8-1.2.1.1.1
a_pmid_2488_5690.48
SDL-AMR-09
Cell @-@ biological phenotypes related to mutant <i> BRAF </i>
GTP
bio.mskcc_0001.55
0-1.1.1 1-1.1 1-1.1.2 1-1.1.2.r 1-1.2 1-1.2.1 1-1.2.1.r 3-1 6-1.2.1.1.r 7-1.2.1.1.1.1 8-1.2.1.1.1 9-1.2.1.1 10-1.2.1.1.2 11-1.2.1.1.2.1.r 12-1.2.1.1.2.1.1.1.1 13-1.2.1.1.2.1 14-1.2.1.1.2.1.2.1 16-1.2.2.1.1.1 18-1.1.3 22-1.1.3.1.3 25-1.1.3.1 28-1.1.3.1.1.1.1 30-1.1.3.1.1.1.1 30-1.1.3.1.2.1.1 32-1.1.3.1.2.1.1 34-1.1.3.1.1.1.1 34-1.1.3.1.2.1.1
This finding is consistent with those of peptide binding studies conducted by Rushworth et al. ( 27 ) indicating that there are multiple points of contact between heterodimerized B @-@ Raf and C @-@ Raf proteins .
SDL-AMR-09
SDL-AMR-09
<sec-title level="1"> RESULTS </sec-title>
pmid_1528_0923.66
1-1 1-1.1 1-1.1.r
15280923
SDL-AMR-09
Previously , we found that in response to growth factor treatment , signaling from C @-@ Raf is downregulated by ERK @-@ dependent feedback phosphorylation on S/TP sites and that C @-@ Raf is subsequently dephosphorylated and returned to a signaling @-@ competent state through the activities of PP2A and the Pin1 prolyl @-@ isomerase ( 8 )
0-1.4 2-1.1 3-1 5-1.2.r 6-1.2.3 7-1.2.3.1.r 8-1.2.3.1.1 9-1.2.3.1.1 10-1.2.3.1 12-1.2.2.4.1 13-1.2.2.4.1 14-1.2.1.2.1 15-1.2.1.2.1 16-1.2.1.2.1 17-1.2.2.4.1 18-1.2.2.4.1 19-1.2.2.4.1 20-1.2.2.4.1 21-1.2.2.4.1 22-1.2.2.4.1 23-1.2.2.4.1 24-1.2.2.4.1 25-1.2.2.4.1 26-1.2.2.4.1 27-1.2.2.4.1 28-1.2.2.4.1 29-1.2.2.4.1 30-1.2.2.4.1 31-1.2.2.4.1 32-1.2.2.4.1 34-1.2.2.4 34-1.2.2.4.r 35-1.2.2.1 36-1.2.2 37-1.2.2.2 38-1.2.2.2.2.r 40-1.2.2.2.2.1 43-1.2.2.2.2 46-1.2.2.3 47-1.2.2.3.1.r 48-1.2.2.3.1.1.1.1 49-1.2.2.3.1 51-1.2.2.3.1.2.1.1 52-1.2.2.3.1.2 54-1.2.2.3.1.2 56-1.3.1.1.1
bio.mskcc_0001.10
FAK
GAP
1-1.4 2-1.4.1.r 3-1.4.1 4-1.4.1.1 6-1.1.1.1.1 7-1.1 8-1 9-1.2.2.1.1.1.1 10-1.2.2.1 11-1.2.2.1.2.1.1 12-1.2.1.1 13-1.3.r 14-1.3.3 15-1.3.1 16-1.3.2.1.1.3.1.1 18-1.3.2.1.1.3 18-1.3.2.1.1.3.2 18-1.3.2.1.1.3.2.r 19-1.3.2 20-1.3.5.2.1 21-1.3 22-1.3 23-1.3.4
SDL-AMR-09
bio.bmtr_0003.4
As shown in Fig. 5A , PLX4032 treatment increased HER3 and HER2 mRNAs in all six BRAF @-@ mutant thyroid cancer cell lines tested .
Cds1
0-1 0-1.1.1.1 3-1.1.1.1.1.1.1 5-1.1.1.1.2.1.1 6-1.1.1 7-1.1 9-1.1.2.2 10-1.1.2 11-1.1.2.1.r 12-1.1.2.1.1.1 13-1.1.2.3.r 14-1.1.2.3.1.2.1 15-1.1.2.3 17-1.1.3.1.1.1
Moreover , the RAS @-@ ASPP interaction enhances the transcription function of p53 in cancer cells [ 2 ] .
SDL-AMR-09
bio.bmtr_0005.20
B-Raf
Finally , CtBP1 and CtBP2 chromatin immunoprecipitation assays showed decreased binding to the HER3 promoter after treatment with PLX4032 ( Fig. 5F ) .
SDL-AMR-09
0-1.1 0-1.1.r 2-1.2.1.1.1.1.1 3-1.2.1.1 4-1.2.1.1.2.1.1 5-1.2.1.2 6-1.2.1 7-1.2 8-1 9-1.3.2 10-1.3 11-1.3.1.r 13-1.3.1.1.1.1.1 14-1.3.1 14-1.3.1.1 14-1.3.1.1.r 15-1.3.2.1 16-1.3.2.1.1 17-1.3.2.1.1.1.r 18-1.3.2.1.1.1.1.1 20-1.4.1 21-1.4.1.1
bio-exp_0001.14
753
threonine
IL-6
bio.mskcc_0001.40
SDL-AMR-09
As shown in Fig. 6A , only mutation of the S151 feedback site , which is in close proximity to the Ras binding domain ( residues 155 to 227 ) , was found to significantly increase binding to activated Ras .
1-1.2 2-1.2.1.r 3-1.2.1 4-1.2.1.1 6-1.1.1.2 7-1.1.1 11-1.1.1.1.3.1 12-1.1.1.1.3 16-1.1.1.1.3.2.r 17-1.1.1.1.3.2 19-1.1.1.1.3.2.1.r 21-1.1.1.1.3.2.1.1.1.1.1 22-1.1.1.1.3.2.1.1 23-1.1.1.1.3.2.1 25-1.1.1.1.3.2.1.2.1.1 25-1.1.1.1.3.2.1.2.1.2 26-1.1.1.1.3.2.1.2.1.1.1.1 27-1.1.1.1.3.2.1.2.1.2.1.r 28-1.1.1.1.3.2.1.2.1.2.1.1 32-1 34-1.1.3 35-1.1 36-1.1.2 37-1.1.2.1.r 38-1.1.2.1.2 39-1.1.2.1.1.1
Tandem mass spectrometric analysis of tryptic fragments from the bands migrating at the positions expected for mono @- and di @- ubiquitinated Ras revealed ubiquitination at Lys residues 104 and 147 of K @-@ Ras , and Lys residues 117 , 147 and 170 for H @-@ Ras ( fig. S1C ) .
SDL-AMR-09
bio.ras_0003.7
0-1.1.2.2 1-1.1.2.1 2-1.1.2 3-1.1 4-1.1.1.r 5-1.1.1.2.1.1 6-1.1.1 7-1.1.1.1.r 9-1.1.1.1 10-1.1.1.1.1 11-1.1.1.1.1.1.1 13-1.1.1.1.1.1 14-1.1.1.1.1.1.1.2 16-1.1.1.1.1.1.1.1.2.1.1 16-1.1.1.1.1.1.1.1.2.1.r 19-1.1.1.1.1.1.1.1.2.1.2 19-1.1.1.1.1.1.1.1.2.1.r 21-1.1.1.1.1.1.1.1.2 21-1.2 22-1.1.1.1.1.1.1.1.1.1 23-1 24-1.1.1.1.1.1.1.1.2 24-1.2 25-1.1.1.1.1.1.1 25-1.2.1.r 26-1.2.1.1.1.1.2.1 26-1.2.1.1.2.1.2.1 26-1.2.1.2.1.1.2.1 26-1.2.1.2.2.1.2.1 27-1.2.1.1.1 27-1.2.1.1.2 27-1.2.1.2.1 27-1.2.1.2.2 28-1.2.1.1.1.1.1 29-1.2.1.1 30-1.2.1.1.2.1.1 32-1.2.1.1.3.1.1 34-1.2.1.1.3.1.1 36-1.2.1 36-1.2.1.1 36-1.2.1.1.r 36-1.2.1.2 37-1.2.1.1.2.1.2.1 37-1.2.1.2.1.1.2.1 37-1.2.1.2.2.1.2.1 37-1.2.1.2.3.1.2.1 38-1.2.1.1.2 38-1.2.1.2.1 38-1.2.1.2.2 38-1.2.1.2.3 39-1.2.1.2.1.1.1 41-1.2.1.2.2.1.1 43-1.2.1.2.3.1.1 44-1.2.1.2.r 45-1.2.1.2.4.1.1 47-1.2.1.2.4.1.1 49-1.3.1 50-1.3.1.1
MEKERK
MKK
Ras
HER2
CtBP
ATM
15280923
SDL-AMR-09
pmid_1528_0923.107
0-1.1.1.1.1 1-1.1.1.2 2-1.1 3-1.1.2.1.1.1 5-1.1.2.1.1.1 6-1.1.2 7-1.1.3.r 8-1.1.3.1.1 10-1.1.3.1.1 12-1.1.3.1.1 13-1.1.3 19-1.2.1 19-1.2.1.r 20-1.2 23-1.3 24-1.3.1.r 25-1.3.1.3 26-1.3.1 27-1.3.1.1.r 28-1.3.1.1.1.1 31-1.3.1.2
U1026 alone inhibited ERK1 @/@ 2 phosphorylation in MDA @-@ MB @-@ 435 cells , with PKI 166 having no effect , as expected from minimal expression of EGFR in these cells .
Induction of the cyclin @-@ dependent kinase inhibitor p27 @<sup> KIP1 </sup> generally corresponded with increases in the proportion of cells in G @<sub> 1 </sub> , as shown for MDA @-@ MB @-@ 231 and SUM149 ( <xref ref-type="fig" rid="fig4"> Figure 4 </xref> ) .
pmid_1528_0923.104
0-1.1 1-1.1.1.r 3-1.1.1.2.1.1.1 5-1.1.1.2.1.1.1 6-1.1.1.2.1.1.2 7-1.1.1 7-1.1.1.2 7-1.1.1.2.r 12-1.3 13-1 14-1.2.r 15-1.2 16-1.2.1.r 18-1.2.1 19-1.2.1.1.r 20-1.2.1.1 27-1.2.1.2.r 27-1.4.r 28-1.4 29-1.4.1.r 30-1.4.1.1.1.1 32-1.4.1.1.1.1 34-1.4.1.1.1.1 35-1.4.1 36-1.4.1.2.1.1 39-1.5.1 40-1.5.1.1
15280923
SDL-AMR-09
a_pmid_2488_5690.47
This was found to be independent of the serum concentration , indicating that the phosphorylation status of Mek and Erk is dependent on mutant <i> BRAF </i> in RKO .
24885690
SDL-AMR-09
0-1.1.2 2-1 5-1.1 5-1.1.1 5-1.1.1.r 6-1.1.3.r 8-1.1.3.1 9-1.1.3 11-1.1.4 12-1.1.4.1.r 14-1.1.4.1.1.1 15-1.1.4.1.1 16-1.1.4.1.1.1.1.r 17-1.1.4.1.1.1.1.1.1.1 18-1.1.4.1.1.1.1 19-1.1.4.1.1.1.1.2.1.1 21-1.1.4.1 22-1.1.4.1.2.r 23-1.1.4.1.2 23-1.1.4.1.2.2 23-1.1.4.1.2.2.r 25-1.1.4.1.2.1.1 27-1.1.4.1.3.r 28-1.1.4.1.3.1.1
Venable et al. ( 66 ) also described an inhibition by ceramide of PLD stimulation by PKC , but ascribed this to an upstream effect on PKC rather than a decrease in the translocation to membranes .
bio.chicago_2015.17165
0-1.1.1.1.1.1.1 1-1.1.1.1 2-1.1.1.1.2.1 4-1.1.1.2.1 6-1.1.3 7-1.1 9-1.1.2 10-1.1.2.1.r 11-1.1.2.1.1.1 12-1.1.2.2.r 13-1.1.2.2.2.1.1 14-1.1.2.2 15-1.1.2.2.1.r 16-1.1.2.2.1.1.1 18-1 19-1.2 21-1.2.3.r 23-1.2.3.2 24-1.2.3 25-1.2.3.1.r 26-1.2.3.1 27-1.2.3.3 30-1.2.3.3.1 31-1.2.3.3.1.1.r 33-1.2.3.3.1.1 34-1.2.3.3.1.1.1.r 35-1.2.3.3.1.1.1
SDL-AMR-09
GDP
His - ubiquitinated K @-@ Ras was subsequently purified with anti - Flag resin .
2-1.1.2 3-1.1.1.1 5-1.1.1.1 7-1.2 7-1.2.r 8-1 9-1.3.r 10-1.3.1 12-1.3.1.1.1.1 13-1.3
bio.ras_0003.4
SDL-AMR-09
Breast_cancer
breast cancer
serine
These data suggest that PI3KC2β binding to nucleotide @-@ free Ras in vivo may prevent loading of nucleotides onto Ras .
bmtr_0006.8
0-1.1.1 1-1.1 2-1 3-1.2.r 4-1.2.1.1.1.1.1 5-1.2.1.1 6-1.2.1.1.2.r 7-1.2.1.1.2.2.1 9-1.2.1.1.2 9-1.2.1.1.2.2 9-1.2.1.1.2.2.r 10-1.2.1.1.2.1.1 11-1.2.1.1.3 12-1.2.1.1.3 13-1.2 14-1.2.1 15-1.2.1.2 16-1.2.1.2.2.r 17-1.2.1.2.2 19-1.2.1.2.1
SDL-AMR-09
histidine
-
0-1 2-1.1.2 2-1.1.2.1 2-1.1.2.1.r 4-1.1.1 4-1.1.1.r 5-1.1 7-1.1.3.2 8-1.1.3 9-1.1.3.1.r 10-1.1.3.1.1.1 12-1.2.r 14-1.2 14-1.2.1 14-1.2.1.r 15-1.2.1.1.r 17-1.2.1.1
bio.bmtr_0004.21
Surprisingly , monoubiquitination did not alter the intrinsic activity of Ras , despite the size of the modification .
SDL-AMR-09
669
Cancer
cancer
i
Raf-1
serine
827
Childs
serine
15
ASPP1
cyclin D3
These results are consistent with a greater fraction of ubiquitinated K @-@ Ras being in the GTP state ( Fig . 2 , A and B ) .
SDL-AMR-09
0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 3-1 6-1.2.1.3.1 6-1.2.1.3.1.1 6-1.2.1.3.1.1.r 7-1.2.1.3 9-1.2.1.2 10-1.2.1.1.1 12-1.2.1.1.1 16-1.2.2.1.1 19-1.3.1.1 19-1.3.1.2 24-1.3.1
bio.bmtr_0001.21
bio.bmtr_0005.3
SDL-AMR-09
It has recently been shown that oncogenic RAS can enhance the apoptotic function of p53 via ASPP1 and ASPP2 .
2-1.2 4-1 5-1.1.r 6-1.1.1.1 6-1.1.1.1.2 6-1.1.1.1.2.1.2.1 6-1.1.1.1.2.r 7-1.1.1.1.1.1 8-1.1 9-1.1.1 11-1.1.1.2.2 12-1.1.1.2 13-1.1.1.2.1.r 14-1.1.1.2.1.1.1 16-1.1.1.3.1.1.1 17-1.1.1.3 18-1.1.1.3.2.1.1
Dvl
V600E
C-terminus
e
Cancer
cancer
p19
Ras
-42
0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 3-1 4-1.2.r 5-1.2.1 5-1.2.1.r 6-1.2.2 7-1.2 8-1.3 9-1.3.1.r 10-1.3.1.1.1.1.1 12-1.3.1 14-1.3.1.1 15-1.3.1.1.2.1.1.1 16-1.3.1.1.2 17-1.3.1.1.2.2.1.1 18-1.3.1.1.4.r 19-1.3.1.1.4 20-1.3.1.1.3.r 21-1.3.1.1.3.1 22-1.3.1.1.3
10729607
SDL-AMR-09
These results are consistent with our previous data showing that PAF is able to translocate PKCa and PKCe from cytosol to plasma membrane
bel_pmid_1072_9607.86
0-1.1.1 1-1.1.1.1.r 2-1.1.1.1.1.1 5-1 6-1.1.3 7-1.1 8-1.1.2 9-1.1.2.1.r 10-1.1.2.1.1.1.1.1.1 12-1.1.2.1.1.1.1.1.1 14-1.1.2.1.1.1.1.2.1.1.1 16-1.1.2.1.1.1 17-1.1.2.1.1.1.2.1.1 19-1.1.2.1.1.1.2.2.1.1.1 21-1.1.2.1 21-1.1.2.1.1 21-1.1.2.1.1.r 22-1.1.2.2.r 23-1.1.2.2.1.1 25-1.1.2.2.1 26-1.1.2.2.2.2.1 27-1.1.2.2.2.2.2 28-1.1.2.2 29-1.1.2.2 33-1.1.3 34-1.1.3.2 34-1.1.3.2.r 35-1.1.3.2.r 38-1.1.3.1.2.1.1.1 40-1.1.3.1.2 41-1.1.3.1 42-1.1.3.1.1.r 43-1.1.3.1.1.1.1.1 44-1.1.3.1.1.1 45-1.1.3.1.1
bio-exp_0001.2
SDL-AMR-09
Upregulation of HER3 has been found to mediate resistance to PI3K @/@ AKT ( 26 ) or HER2 ( 27 ) inhibitors in HER2 @-@ amplified breast cancer cell lines , which is caused in part through a FoxO3A @-@ dependent induction of HER3 gene transcription .
B-Raf
SDL-AMR-09
bio-exp_0001.8
This region does not contain any predicted FoxO binding sites .
0-1.2.1 1-1.2 3-1.1 3-1.1.r 4-1 5-1.3.1 6-1.3.2 7-1.3.3.1.1.1 8-1.3.3 9-1.3
SDL-AMR-09
2-1.1.1 3-1.1 5-1 9-1.2.1 10-1.2 13-1.2.2.2.1.1 14-1.2.2 15-1.2.2.r
bio.bmtr_0001.4
His @-@ ubiquitinated proteins were purified by Co2+ metal affinity chromatography in 8M urea denaturing conditions .
151
serine
24885690
0-1.3.1.3.r 1-1.3.1.1.1 2-1.3.1.1 4-1.3.1.2 5-1.3.1 5-1.3.1.3.r 7-1.3.1.3 8-1.3.1.3.2 9-1.3.1.3.2.1 12-1.3.1.3.2.1.1.1.1 13-1.3.1.3.2.1.1 16-1.3.1.4.1.1.1 20-1.1 21-1.4 22-1 23-1.2.1.1.1 24-1.2.1 25-1.2
a_pmid_2488_5690.62
SDL-AMR-09
Since serum starvation is often used to model apoptosis mediated via the PUMA pathway [ @<xref ref-type="bibr" rid="B26"> 26 </xref>@ ] , we also analyzed PUMA protein levels .
BRAF
e
SDL-AMR-09
1-1.1.1.3.1.1 3-1.1.1.3.1.1 6-1.1.1.4.1.1.1.1 8-1.1.1.4.1 9-1.1.1.4 13-1.1.1 18-1.1 20-1 21-1.2.1.1 27-1.2 31-1.2.1.2 32-1.2.1.2 33-1.2.1
For B @-@ Raf , two ERK @-@ dependent feedback sites , S750 and T753 , have been identified , and phosphorylation of these sites has been reported to have a negative regulatory effect
bio.mskcc_0001.8
ERK2
-
bio-kappa_0001.13
In addition to promoting C @-@ Raf activation , PP2A is also able to dephosphorylate Erk - dependent sites on C @-@ Raf .
SDL-AMR-09
0-1 1-1 3-1.1 4-1.1.2.1 5-1.1.2.1 6-1.1.2.1 7-1.1.2 9-1.2.1.2.1.1 11-1.2.2 12-1.2 14-1.2.1 15-1.2.1.1.1.1.1.1 17-1.2.1.1.1 18-1.2.1.1 19-1.2.1.1.2.r 20-1.2.1.1.2.1.1 22-1.2.1.1.2.1.1
However , replacement with the EGFR ( exon19 del ) T669A mutant led to increased tyrosine phosphorylation of both EGFR and ERBB3 , and activation of PI3K @/@ AKT signaling , mimicking the effect of MEK inhibition ( Figure 6C ) .
bio.bmtr_0002.18
0-1.3 2-1.1 3-1.1.1.r 5-1.1.1.1.1 10-1.1.1.2.1 11-1.1.1 11-1.1.1.2 11-1.1.1.2.r 12-1 13-1.2.r 14-1.2.1 15-1.2.1.1.1.1.1.1 15-1.2.1.1.2.1.1.1 16-1.2.1.1.1 16-1.2.1.1.2 19-1.2.1.1.1.1.2.1.1 20-1.2.1.1 21-1.2.1.1.2.1.2.1.1 23-1.2 24-1.2.2 25-1.2.2.1.r 26-1.2.2.1.1.1 28-1.2.2.1.1.1 29-1.2.2.1.2 31-1.2.3 33-1.2.3.1 34-1.2.3.1.1.r 35-1.2.3.1.1.1.1.1 36-1.2.3.1.1 38-1.4.1 39-1.4.1.1
SDL-AMR-09
2+
bio.bmtr_0005.19
SDL-AMR-09
We and others have recently shown that ASPP2 can potentiate RAS signaling by binding directly via the ASPP2 N @-@ terminus [ 2,6 ] .
0-1.1.1 1-1.1 2-1.1.2.1 4-1.3 5-1 6-1.2.r 7-1.2.1.2.1.1 8-1.2 9-1.2.1 10-1.2.1.1.1.1.1 11-1.2.1.1 12-1.2.1.3.r 13-1.2.1.3 14-1.2.1.3.3 17-1.2.1.3.2.2 18-1.2.1.3.2.1.1 20-1.2.1.3.2.1.1
Because PLD activates PKC through the formation of diacylglycerol in VSMCs , 47 PLD also may contribute to this suppression .
0-1 1-1.1.1.1.1 2-1.1 3-1.1.2.1.1 6-1.1.3 7-1.1.3.1.r 8-1.1.3.1.1.1 12-1.1.4.1.1.1 13-1.1.1.1.1 14-1.2.2 15-1.2 16-1.2.1 17-1.2.1.2.r 18-1.2.1.2.1 19-1.2.1.2
bio.chicago_2015.17114
SDL-AMR-09
H2O2
Hydrogen_peroxide
8A
e
thyroid cancer
Thyroid_cancer
PP2A
HER3
a_pmid_2488_5690.46
While the expression of Mek 1 @/@ 2 and Erk 1 @/@ 2 was independent of serum concentration and <i> BRAF </i> status , the phosphorylation of these effector kinases was constantly active in the <i> BRAF </i>@ -@ mutant clones but low in <i> BRAF </i>@ -@ wild @-@ type cells ( Figure <xref ref-type="fig" rid="F1"> 1 </xref>@ C ) .
0-1 2-1.2.2 7-1.2.2.1.1.1.1 7-1.2.2.1.2.1.1 8-1.2.2.1 12-1.2.2.1.1.1.1 12-1.2.2.1.2.1.1 14-1.2 14-1.2.1 14-1.2.1.r 15-1.2.3.r 16-1.2.3.1.1 17-1.2.3.1 18-1.2.3 20-1.2.3.2.1.1.1 22-1.2.3.2 25-1.1.1.1 29-1.1.1.1.1 30-1.1.1.1.r 31-1.1.1.2 31-1.1.1.2.r 32-1.1.1 36-1.1.1.3.1.1.1 39-1.1.1.3.1 39-1.1.1.3.1.2 39-1.1.1.3.1.2.r 40-1.1.1.3 41-1.1 42-1.1.2 45-1.1.2.1.1.1.1 48-1.1.2.1.1.2 50-1.1.2.1.1.2 51-1.1.2.1 53-1.3.1
24885690
SDL-AMR-09
The tryptic peptide with ubiquitination at Lys147 ( K147 ) was the most frequently observed peptide for both K @-@ Ras and H @-@ Ras , while Lys117 appeared as a secondary major ubiquitination site in H @-@ Ras .
bio.bmtr_0001.9
1-1.1.3.2.1.1.1 2-1.1 2-1.1.3 4-1.1.3.1.3 10-1.1.3.r 12-1.1.1.1.1 13-1.1.1.1 14-1.1.1 15-1.1 15-1.1.3 18-1.1.2.1.1.1.1 20-1.1.2.1.1.1.1 20-1.1.2.1.2.1.1 22-1.1.2.1.2.1.1 24-1.1.2.1.1.1.1 24-1.1.2.1.2.1.1 26-1 28-1.2 29-1.2.1.r 31-1.2.1.3 32-1.2.1.2 33-1.2.1.1 34-1.2.1 36-1.1.2.1.2.1.1 38-1.1.2.1.1.1.1 38-1.1.2.1.2.1.1
SDL-AMR-09
-
central armadillo repeat
cysteine
U0126
1
0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 2-1 3-1.2.r 4-1.2.2 8-1.2.2.3 10-1.1.2 13-1.2.2.2.1.1 13-1.2.3.1.2.1 15-1.2.2.2.2.1 16-1.2.2.2.1 16-1.2.2.2.2 19-1.2.1 19-1.2.1.r 20-1.2 22-1.2.3 25-1.2.3.2.r 26-1.2.3.2.2.1.1 27-1.2.3.2
bio.bmtr_0004.11
SDL-AMR-09
These results indicate that variations in the linker length on this scale ( 1 @-@ 2 bonds ) do not influence the sensitivity of mUbRas to GAP downregulation .
Ras
STAT3
PSP
1
2
PSP
14-3-3
1
doxycycline
Raf
3
28
p2
HKe3 ER
G1
B-Raf
MEK2
TBP
1B
10744722
As shown in Fig. 3A in normal cells , IR causes activation of Chk2 @/@ Cds1 ( lane 2 ) , and this activation is inhibited by prior treatment of cells with caffeine ( lane 4 ) .
bel_pmid_1074_4722.15494
0-1.2.1.3.r 1-1.3 2-1.3.1.r 3-1.3.1 4-1.3.1.1 6-1.4.1 7-1.4 9-1.1.1 9-1.1.1.1 9-1.1.1.1.r 10-1.1 11-1.1.2 13-1.1.2.1.1.1.1 15-1.1.2.1.2.1.1 17-1.1.3.1 18-1.1.3.1.1 23-1.1.2 25-1.2 27-1.2.1.3 28-1.2.1 29-1.2.1.1.r 30-1.2.1.1 31-1.2.1.2.r 32-1.2.1.2 34-1.2.3.1 35-1.2.3.1.1
SDL-AMR-09
DLT
In contrast to the GEF @-@ Ras complex , which is disrupted by addition of guanine nucleotides , the PI3KC2β RBD @-@ Ras complex is stable even in the presence of high concentrations of GTP or GDP .
bmtr_0006.7
SDL-AMR-09
1-1.2 2-1.2.1.r 4-1.2.1.1.1.1 6-1.2.1.2 7-1.2.1 11-1.2.1.3 12-1.2.1.3.1.r 13-1.2.1.3.1 14-1.2.1.3.1.1.r 15-1.2.1.3.1.1.1 16-1.2.1.3.1.1 19-1.1.1.2.1.1 20-1.1.1.1.1 22-1.1.2.1.1 23-1.1 25-1 26-1.3.2 29-1.3 30-1.3.1.r 31-1.3.1.2 32-1.3.1 33-1.3.1.1.r 34-1.3.1.1.1.1.1 35-1.3.1.1 36-1.3.1.1.2.2.1
gamma-tubulin
12V
SDL-AMR-09
0-1.4 2-1.1 5-1.3 5-1.3.r 6-1 7-1.2.1.1.1.1 8-1.2.1 9-1.2 10-1.2.2 11-1.2.r 12-1.2.3.2.2.1 13-1.2.3.2.2.2 14-1.2.3
bio.bmtr_0003.19
Accordingly , knockdown of CTBPs acutely induced HER3 expression and phosphorylation in thyroid cancer cells .
tyrosine
1
HER3
MDA-MB-468
SRC-1
Colorectal_cancer
colorectal cancer
ERK12
-
6C
p
Ras
actin
Colorectal_cancer
colon cancer
C-terminus
Gly13
-
19
e
RBO-2
c
-
RKO
1A
pmid_1528_0923.98
The addition of U0126 to 0.5 or 5.0 <i> μ </i>@ <sc> M </sc> PKI166 significantly increased the growth inhibition produced by the receptor tyrosine kinase inhibitor alone ( <xref ref-type="table" rid="tbl1"> Table 1 </xref> ) .
SDL-AMR-09
1-1.1 2-1.1.1.r 3-1.1.1.1.1 4-1.1.2.r 5-1.1.2.1.2.1 6-1.1.2 14-1.1.2.1.1.1 14-1.1.2.2.1.1 15-1.3 16-1 18-1.2.1 19-1.2 20-1.2.2 21-1.2.2.1.r 23-1.2.2.1.1.1.1.1 24-1.2.2.1.1.1.1.2 25-1.2.2.1.1.1.1.3 26-1.2.2.1 26-1.2.2.1.1 26-1.2.2.1.1.r 27-1.2.2.1.2 30-1.4.1 31-1.4.1.1
15280923
p42ERK2
MEK
RAS
20
0-1 4-1.1 4-1.1.1 4-1.1.1.r 5-1.1.3.r 6-1.1.3.2.1.1.1 8-1.1.3.2 9-1.1.3 11-1.1.4 12-1.1.4.1.3 14-1.1.4.1.3 14-1.1.4.1.3.1.2.1 15-1.1.2.1.1 15-1.1.4.1.2.1.1 17-1.1.4.1.1 18-1.1.4.1
Therefore , mUbRas is insensitive to GAP @-@ mediated regulation , similar to an oncogenic Ras @-@ G12V mutation .
bio.bmtr_0004.7
SDL-AMR-09
bio.mskcc_0001.56
SDL-AMR-09
0-1.3 0-1.3.r 2-1.1.2 3-1.1.1.1 4-1.1.1 5-1.1 6-1.4 7-1 10-1.2.1.1.2.1 12-1.2.1.1.2.1 12-1.2.1.2.2.1 13-1.2.1 14-1.2.1.2.2.1 16-1.6.1.1.1.1.2.1 17-1.6.1.1.1.1 19-1.2.2 20-1.2 23-1.5.1.1.1 26-1.6 28-1.6.1.1.1.2 29-1.6.1.1.1 32-1.6.1.1.1.1.2.1 33-1.6.1.1.1.1 34-1.6.1 35-1.6.1.1 36-1.6.1.1.1.1.2.1 38-1.6.1.1.3 39-1.6.1.1.3
Interestingly , these peptide binding studies also indicate that homodimerized B @-@ Raf and C @-@ Raf proteins have multiple contact points ( 27 ) , suggesting that feedback phosphorylation of the Raf proteins may disrupt Raf homodimers as well
0-1.2 1-1.2.1 3-1.1.2.1.1 8-1.1.1.1.1.1.1 9-1.1.1.1 10-1.1.1 12-1.1.1.2 13-1.1.1.3 14-1.1.1.3.1.r 15-1.1.1.3.1.1.1.1 16-1.1.1.3.1 18-1.1.3.2 19-1.1.3 20-1.1.3.1.r 21-1.1.3.1.2 22-1.1.3.1 23-1.1.3.1 24-1.1.3.1.1.1 25-1.1.3.1.1 26-1.1.3.1.3.r 27-1.1.3.1.3.1.1 28-1.1.3.1.3
10640734
SDL-AMR-09
bel_pmid_1064_0734.39822
Taken together , CD72 down @-@ modulates both ERK activation and Ca2+ mobilization induced by BCR ligation , strongly suggesting that CD72 negatively regulates BCR signaling in K46^mA cells .
0-1.1 2-1.4 3-1 5-1.5.r 7-1.5.1.1.1 8-1.5.1 8-1.5.1.1 8-1.5.1.1.r 9-1.5 12-1.2.1.1.1 13-1.2 16-1.3.1.1 17-1.3.1 18-1.3.3.1 19-1.3.3 20-1.3 22-1.3.2.2.1.1.1 24-1.3.2.2.1.1.1 26-1.3.2.2 27-1.3.2.1.1.1.1.1 28-1.3.2.1 28-1.3.2.1.1 28-1.3.2.1.1.r 29-1.3.2
10737606
SDL-AMR-09
We have further identified , in the GFAP promoter region , a STAT3 site at which nucleotide substitutions almost completely abolished the IL @-@ 11 @-@ induced GFAP promoter activation .
bel_pmid_1073_7606.7132
Thus , expression of CD72 appears to negatively regulate BCR @-@ mediated Ca2+ mobilization in K46^mA cells .
SDL-AMR-09
2-1.1.1.2 3-1.1.1.2.1.r 4-1.1.1.2.1.1.1 5-1.1 7-1.1.1 8-1.1.1 9-1.1.1.1.2.1.1.1 11-1.1.1.1.2 13-1.1.1.1 14-1.1.1.3.r 15-1.1.1.3.1.1 16-1.1.1.3
bel_pmid_1064_0734.39820
10640734
S729A
SDL-AMR-09
0-1.1 1-1.1.1.r 2-1.1.1.1.1 3-1.1.2.r 4-1.1.2.1.1 6-1.1.2.1.1 7-1.1.2 9-1 10-1.2.r 11-1.2.1 11-1.2.1.r 12-1.2.3 13-1.2.2.1 15-1.2.2 16-1.2 18-1.3.1.1
Phosphorylation of ASPP2 by RAS @/@ MAPK Pathway Is Critical for Its Full Pro @-@ Apoptotic Function ( PMC3847091 )
bmtr_0007.1
EGFR
BRAF
A further negative regulator of the cascade , at the level of C @-@ Raf , is Protein phosphatase 5 ( PP5 ) , which associates with C @-@ Raf via its N @-@ terminal tetratricopeptide ( TPR ) domain in growth factor stimulated cells .
bio-kappa_0001.16
1-1.1.3 2-1 3-1 4-1.2.r 6-1.2 11-1.2.1.r 12-1.2.1 13-1.2.1 14-1.2.1 17-1.1.1.1 18-1.1.1.2 19-1.1.1.3 25-1.1 25-1.1.2 25-1.1.2.r 26-1.1.2.1.r 26-1.1.2.3.r 27-1.1.2.1.1.1 29-1.1.2.1.1.1 31-1.1.2.3.2.2 31-1.1.2.3.2.2.r 32-1.1.2.3.2.1.1 34-1.1.2.3.2.1.1 35-1.1.2.3.1.1 39-1.1.2.3.1.2 40-1.1.2.2.r 41-1.1.2.2.1.1 42-1.1.2.2.1.1 43-1.1.2.2.1 44-1.1.2.2
SDL-AMR-09
Guichet
MDA-MB-231
1-1.3 3-1.3.2 4-1.3.2.1.r 5-1.3.2.1 6-1.3.2.2.r 7-1.3.2.2.1.1.1 8-1.3.2.2 10-1.1.1 11-1.1 12-1.1.2.1.1.2 12-1.1.2.1.3.2 14-1.1.2.1.1.2 14-1.1.2.1.3.2 15-1.1.2.1.1.1.1 15-1.1.2.1.2.1.1 15-1.1.2.1.3.1.1 17-1.1.2.1.1.1.1 17-1.1.2.1.2.1.1 17-1.1.2.1.3.1.1 19-1.1.2.1.2 19-1.1.2.1.2.2 19-1.1.2.1.2.2.1.2.1 19-1.1.2.1.2.2.r 20-1.1.2.1.2.3.1 22-1.1.2.1.2.1.1 24-1.1.2.1.2.1.1 25-1.1.2.1.2.3 26-1.1.2.1 28-1.1.2.1.3.3 29-1.1.2.1.3.4 31-1.1.2.1.1.2 31-1.1.2.1.3.2 33-1.1.2.1.1.2 33-1.1.2.1.3.2 34-1.1.2.1.1.1.1 34-1.1.2.1.2.1.1 34-1.1.2.1.3.1.1 36-1.1.2.1.1.1.1 36-1.1.2.1.2.1.1 36-1.1.2.1.3.1.1 37-1.1.3.r 38-1.1.3.1.1.2 38-1.1.3.1.1.2.1.1 40-1.1.3.1.1.1.1 41-1.1.3.1 42-1.1.3 43-1 43-1.1.2 44-1.2 45-1.2.2.1.1.1 46-1.2.2.1.1 47-1.2.2.1 51-1.2.2 52-1.2.2.2.1.1.1 53-1.2.2.2.1.1 54-1.2.2.2.1 55-1.2.2.2 60-1.2.3 62-1.2.3.2 63-1.2.3.2 64-1.2.3.2.1.2 64-1.2.3.2.1.2.1.1 64-1.2.3.2.2.2 64-1.2.3.2.2.2.1.1 66-1.2.3.2.1.1.1 68-1.2.3.2.1.2 68-1.2.3.2.1.2.1.1 68-1.2.3.2.2.2 68-1.2.3.2.2.2.1.1 70-1.2.3.2.2.1.1 74-1.1 79-1.1.2.1.1.1.1 79-1.1.2.1.2.1.1 79-1.1.2.1.3.1.1 81-1.1.2.1.1.1.1 81-1.1.2.1.2.1.1 81-1.1.2.1.3.1.1
To examine the effect of ubiquitination on GTP loading , we purified wild @-@ type K @-@ Ras , oncogenic G12V @-@ K @-@ Ras mutant or the ubiquitinated subfraction of wild @-@ type K @-@ Ras from 32P @-@ orthophosphate labeled cells and utilized thin layer chromatography ( TLC ) and high performance liquid chromatography ( HPLC ) to assess the ratio of 32P @-@ GTP to 32P @-@ GDP that co @-@ purified with each form of K @-@ Ras .
bio.bmtr_0001.10
SDL-AMR-09
SDL-AMR-09
bel_pmid_1069_9758.36926
0-1.2.2.1.1.1.1.1 1-1.1.3 3-1.1.2.1.1 5-1.1.2.1.1 6-1.1 7-1.1.1.1.1 10-1.1.1.2.2 11-1.1.1.2 12-1.1.1.2.1.r 13-1.1.1.2.1.1.1.1 14-1.1.1.2.1 15-1.1.1.2.1.2.1.1 20-1.2.1.1.1.1.1 21-1.2.1.1 22-1.2.1.1.2.1.1 23-1.2.1 24-1.2.1.2.1.1.1 25-1.2.1.2 25-1.2.2.1.1 26-1.2.1.2.2.1.1 27-1.2 28-1.2.2 31-1.2.2.2.1.1.1 32-1.2.2.2.1.1.2 33-1.2.2.2.1 35-1.2.2.1.1.1.1.1 35-1.2.2.1.1.2.1.1 39-1.2.2.1.1.2.1.1
10699758
Once activated , Raf @-@ 1 phosphorylates serines in the catalytic sites of MKK @/@ MEK [ 345,367 ] . MKK1 @/@ MEK1 and MKK2 @/@ MEK2 activate members of the MAP kinase family ( ERK @-@ 1/ERK @-@ 2 ) ,
The combination of agents significantly increased the antiproliferative action of PKI166 at the 0.5 and 5.0 <i> μ </i>@ <sc> M </sc> doses in cells expressing higher levels of EGFR or HER2 ( SUM149 , MDA @-@ MB @-@ 468 , SKBR3 ) , including MDA @-@ MB @-@ 231 cells .
SDL-AMR-09
1-1.1 2-1.1.1.r 3-1.1.1 4-1.3 5-1 7-1.2.2 7-1.2.2.1 7-1.2.2.1.r 8-1.2 9-1.2.1.r 10-1.2.1.1.1 13-1.2.1.2.1.1.1 14-1.2.1.2.1 22-1.2.1 22-1.2.1.2 22-1.2.1.2.r 23-1.4.r 24-1.4 25-1.4.1 26-1.4.1.1.1.2 26-1.4.1.1.1.2.1 26-1.4.1.1.1.2.1.r 27-1.4.1.1.1 27-1.4.1.1.2 28-1.4.1.1.1.1.r 29-1.4.1.1.1.1.1.1 30-1.4.1.1 31-1.4.1.1.2.1.1.1 33-1.4.2.1.1.1.1 35-1.4.2.1.2.1.1 37-1.4.2.1.2.1.1 39-1.4.2.1.2.1.1 41-1.4.2.1.3.1.1 44-1.4.3 45-1.4.3.1.1.1 47-1.4.3.1.1.1 49-1.4.3.1.1.1 50-1.4
pmid_1528_0923.96
15280923
2
bio.chicago_2015.17152
SDL-AMR-09
Whether PKC regulation of DAT and other neurotransmitter transporters is due to direct phosphorylation of the transporter remains unclear .
0-1.1.1 0-1.1.1.r 1-1.1.3.1.1.1 2-1.1.3 3-1.1.3.2.r 4-1.1.3.2.1.1.1 5-1.1.3.2 6-1.1.3.2.2.2 7-1.1.3.2.2.1.1 8-1.1.3.2.2.1.2 10-1.1 11-1.1 12-1.1.2.2 13-1.1.2 16-1.1.3.2.2.1.2 17-1 18-1.2 18-1.2.1 18-1.2.1.r
e2
interrogative
threonine
bio.mskcc_0001.18
Consistent with these data , we found that B @-@ Raf interacted with C @-@ Raf in an inducible and transient manner following growth factor treatment ( Fig . 3B and C ) .
0-1.3 1-1.3.1.r 2-1.3.1.1 3-1.3.1 5-1.1 6-1 7-1.2.r 8-1.2.1.1.1 10-1.2.1.1.1 10-1.2.2.1.1 11-1.2 12-1.2.2.r 13-1.2.2.1.1 15-1.2.1.1.1 15-1.2.2.1.1 16-1.2.3.r 18-1.2.3 20-1.2.4 22-1.2.5 23-1.2.5.1.1 24-1.2.5.1.1 25-1.2.5.1 27-1.4.1.1 27-1.4.1.2 29-1.4.1.1.1 30-1.4.1 31-1.2.2.1.1
SDL-AMR-09
669
threonine
oligodeoxynucleotide
bio-kappa_0001.27
In principle , these reactions are fast and fully reversible , so that the GEF merely acts as a catalyst to increase the rate at which equilibrium between the GDP @- and GTP - bound forms of the protein is reached .
SDL-AMR-09
0-1.3 1-1.3 3-1.1.1.1 4-1.1.1 6-1.1 7-1 8-1.2.1.2 11-1.4 12-1.4.1.4.r 14-1.4.1.1.1.1 15-1.4.1.3 16-1.4.1 21-1.4.1.4 23-1.4.1.4.2 29-1.4.1.4.2.1.1.1.1.1.1.1.1 31-1.4.1.4.2.1.1.1 32-1.4.1.4.2.1.1.1.2.1.1.1.1 34-1.4.1.4.2.1.1.1.1.1 34-1.4.1.4.2.1.1.1.2.1 38-1.4.1.4.2.1.1.1.1 38-1.4.1.4.2.1.1.1.2 40-1.4.1.4.2.1
2005
bio-kappa_0001.20
SDL-AMR-09
1-1.1.1.1 2-1.1.1.2 4-1.1.1.2 5-1 6-1.2.r 7-1.2.1 8-1.2
The guanine nucleotide @-@ binding switch in three dimensions .
Chk2
10744722
bel_pmid_1074_4722.15496
Immediately after IR , an increase in serine 216 @-@ phosphorylated Cdc25C was observed in the nuclear fraction ( Fig . 1B , lane 2 ) , and prior treatment of cells with caffeine inhibited this increase ( Fig . 1B , lane 4 ) .
SDL-AMR-09
0-1.1.3.2 1-1.1.3 2-1.1.3.1 2-1.1.3.1.1 2-1.1.3.1.1.r 5-1.1.1 7-1.1.1.1.2.2.1 8-1.1.1.1.2.1 10-1.1.1.1.2.3 11-1.1.1.1.1.1 13-1.1 14-1.1.2.r 16-1.1.2.1 17-1.1.2 19-1.2.3.1.1 21-1.2.3.1.1.1 23-1.1.4.1.2 24-1.1.4.1.2.1 27-1 27-1.1.4.1 28-1.2.1.3 29-1.2.1 30-1.2.1.1.r 31-1.2.1.1 32-1.2.1.2.r 33-1.2.1.2 34-1.2 36-1.1.1 38-1.1.4.1.1 40-1.1.4.1.1.1 42-1.2.3.1.2 43-1.2.3.1.2.1
MEK
0-1.1.1.1.1.1 0-1.1.1.2.1.1 0-1.1.1.3.1.1 1-1.1 2-1.1.1.r 3-1.1.1.1.2.1.1 5-1.1.1.2.2.1.1 7-1.1.1 8-1.1.1.3.2.1.1 10-1 12-1.2.1.1.1 14-1.2.1.1.1 15-1.2 16-1.2.2.r 17-1.2.2.2 18-1.2.2.1.1 20-1.2.2.1.1 22-1.2.2.3.1.1 23-1.2.2.3 24-1.2.2.3.2 25-1.2.2.3.2.1.r 27-1.2.2.3.2.1.1.1.1.2 28-1.2.2.3.2.1.1.1.1.1.1 29-1.2.2.3.2.1 30-1.2.2.3.2.1.2.1.1.1.1 31-1.2.2.3.2.1.1.1 31-1.2.2.3.2.1.2.1 32-1.2.2.3.2.1.1 32-1.2.2.3.2.1.2
10747872
bel_pmid_1074_7872.21236
SDL-AMR-09
tyrosine phosphorylation of STAT3 , JAK1 , and JAK2 was increased upon IGF @-@ I stimulation of endogenous IGF @-@ IR in 293T cells transfected with the respective STAT or JAK expression vector .
C-Raf
0-1.1.1 1-1.1 3-1 4-1.2.r 6-1.2 6-1.2.1 6-1.2.1.r 7-1.2.1.1.r 8-1.2.1.1.1.1.1 9-1.2.1.1 11-1.3 12-1.3.1.1.1.1.1 13-1.3.1.1 14-1.3.1 15-1.2.1.1.1.r 15-1.3.2.r 16-1.3.2 17-1.3.2.1 18-1.3.2.1.1.r 19-1.3.2.1.1 20-1.2.1.1.1.r 21-1.3.2.1.1.1.1.2.1 22-1.3.2.1.1.1.1.2 23-1.3.2.1.1.1.1.1.1
15280923
pmid_1528_0923.82
SDL-AMR-09
Growth inhibition was determined from the results of MTT assays , comparing PKI166 treated cells with cells exposed to medium with 0.1 % DMSO .
SDL-AMR-09
0-1.2.1.1.1 2-1.2.1.1.1 3-1.2 4-1.2.2.1 6-1.3.1 7-1.3.1.1.r 8-1.3.1.1.3 9-1.3.1.1 10-1.3.1.1.2.r 11-1.3.1.1.2.1.1.1 12-1.3.1.1.2 13-1.3.1.1.1.r 14-1.3.1.1.1.1.1.1.1.1 15-1.3.1.1.1.1.1 16-1.3.1.1.1.1.1.2.1.1 17-1.3.1.1.1 17-1.3.1.1.1.1 17-1.3.1.1.1.1.r 18-1.3 19-1.3.2.1 19-1.3.2.1.r 20-1.3.2.2 20-1.3.2.2.1 20-1.3.2.2.1.r 21-1.3.2 22-1.3.2.3.r 23-1.3.2.3.3.1.1 24-1.3.2.3.3 24-1.3.2.3.3.2 24-1.3.2.3.3.2.r 25-1.3.2.3.2 28-1.1
bio.bmtr_0003.1
Montero @-@ Conde et al. “ Relief of feedback inhibition of HER3 transcription by RAF and MEK inhibitors attenuates their antitumor effects in BRAF mutant thyroid carcinomas.” ( PMC3651738 )
1500
-1
Flag
The ability to form H @-@ DNA cannot substitute for GAGA factor binding to the ( CT ) n sequence .
1-1.2.1 3-1.2.1.1 4-1.2.1.1.1.1.1 6-1.2.1.1.1.1.1 7-1 7-1.1 7-1.1.r 8-1.2 9-1.2.2.r 10-1.2.2.1.1.1 11-1.2.2.1.1.2 12-1.2.2 19-1.2.2.2.1.2
SDL-AMR-09
bio.chicago_2015.17831
Flag
1
2-1.3 5-1 6-1.2.2 7-1.2 8-1.2.1.r 9-1.2.1.1.1 10-1.3 11-1.3.1.r 12-1.3.1.3 12-1.3.1.3.1 12-1.3.1.3.1.r 13-1.3.1.2 14-1.1 14-1.3.1 15-1.3.1.1.r 16-1.3.1.1.1.1.1 18-1.3.1.1 19-1.3.1.1.2.1.1 21-1.3.1.3.2.r 23-1.3.1.3.2.1.2 24-1.3.1.3.2.1.2 25-1.3.1.3.2 26-1.3.1.3.2.3.2.1 26-1.3.1.3.2.3.2.1.r 27-1.3.1.3.2.3.2 28-1.3.1.3.2.1.1.1 28-1.3.1.3.2.2.1.1 28-1.3.1.3.2.3.1.1 30-1.3.1.3.2.2.2.1 31-1.3.1.3.2 32-1.3.1.3.2.3.3.1
SDL-AMR-09
bmtr_0006.11
As a result , BiFC traps this form of Ras resulting in greater fluorescence complementation for Ras17N ( and Ras17N/69N ) compared to wild type or constitutively activated Ras ( 61L or 12V ) .
APP
Here we find that both normal and oncogenic B @-@ Raf proteins are phosphorylated on four S/TP sites ( S151 , T401 , S750 , and T753 ) by activated ERK .
SDL-AMR-09
bio.mskcc_0001.9
0-1.3 1-1.1 2-1 5-1.2.3.1 7-1.2.3.2 7-1.2.3.2.2.2.1 8-1.2.1.5.1.1 10-1.2.1.5.1.1 13-1.2 25-1.2.1 28-1.2.2.r 29-1.2.2.2 30-1.2.2.1.1
MDA @-@ MB @-@ 231 and MDA @-@ MB @-@ 435 tumour lysates showed high levels of p @-@ ERK1 @/@ 2 in comparison to MDA @-@ MB @-@ 468 and GI101A tumours ( <xref ref-type="fig" rid="fig1"> Figure 1B </xref> ) .
pmid_1528_0923.71
SDL-AMR-09
0-1.1.1.1.1.1 2-1.1.1.1.1.1 4-1.1.1.1.1.1 5-1.1.1 6-1.1.1.1.1.1 6-1.1.1.2.1.1 8-1.1.1.1.1.1 8-1.1.1.2.1.1 10-1.1.1.2.1.1 11-1.1.1.3 12-1.1 13-1 14-1.2.1 15-1.2 16-1.2.2.r 17-1.2.2.2 19-1.2.2.1.1 21-1.2.2.1.1 22-1.2.3.r 23-1.2.3 24-1.2.3.1.r 25-1.2.3.1.1.1.1 27-1.2.3.1.1.1.1 29-1.2.3.1.1.1.1 30-1.2.3.1 31-1.2.3.1.2.1.1 32-1.2.3.1.3 35-1.3.1 36-1.3.1.1
15280923
24885690
Consistent with RKO modeling a distinct subpopulation of patients characterized by the presence of certain molecular features and the absence of others [ @<xref ref-type="bibr" rid="B7"> 7 </xref>@ ] , no implication of p53 in apoptosis was observed ( Figure <xref ref-type="fig" rid="F2"> 2 </xref>@ H ) .
a_pmid_2488_5690.61
SDL-AMR-09
0-1.2 1-1.2.1.r 2-1.2.1.1.1.1 3-1.2.1 5-1.2.1.2.2 6-1.2.1.2 7-1.2.1.2.1.r 8-1.2.1.2.1 9-1.2.1.2.3 13-1.2.1.2.3.1.r 14-1.2.1.2.3.1.1.2.2 15-1.2.1.2.3.1.1.2.1 16-1.2.1.2.3.1.1.2 16-1.2.1.2.3.1.2.2 17-1.2.1.2.3.1 20-1.2.1.2.3.1.2.2.2.r 21-1.2.1.2.3.1.2.2.2 24-1.2.1.3.1.1.1 28-1.1.1 28-1.1.1.r 29-1.1 30-1.1.2.r 31-1.1.2.1.1 32-1.1.3.r 33-1.1.3 35-1 37-1.3.1
bmtr_0007.4
To test the efficacy of the purified phospho @-@ specific
1-1 3-1.1 6-1.1.1.1 7-1.1.1.2.1 9-1.1.1.2
SDL-AMR-09
1
10660621
bel_pmid_1066_0621.6864
SDL-AMR-09
0-1.1.1 1-1.1.1.1.r 2-1.1.1.1 3-1.1.1.1.1 4-1.1.1.1.1.1.1.1 6-1.1.1.1.1.1.1.1 7-1.1.1.2.r 8-1.1.1.2.1.1 9-1.1.1.2.1.2 10-1.1.1.2.1.3 11-1.1 13-1.1.2.2.1 15-1.1.2.2 17-1.1.2.3.1.1.1 18-1.1.2.3.1.1.2 20-1.1.2.3 21-1.1.2 22-1.1.2.1.r 24-1.1.2.1 24-1.1.2.1.2 24-1.1.2.1.2.r 25-1.1.2.1.1.1 26-1.1.2.1.1.2 28-1.2.1.1.2 29-1.2.1.1 29-1.2.1.1.1 29-1.2.1.1.1.r 30-1.2.1 31-1.2.1.2 32-1.2.1.3.r 34-1.2.1.3.2 35-1.2.1.3 36-1.2.1.3.1.r 37-1.2.1.3.1.1.1 39-1.2.1.3.1.1.1 40-1.2 41-1.2.2 43-1.2.2.2 47-1.2.2.3 48-1.2.2.3.1.1 49-1.2.2.3.1 51-1.2.2.3.1.2 52-1.2.2.3.1.2.1.1 53-1.2.2.3.1.2.1.1 54-1.2.2.3.1.2.1.1 55-1.2.2.3.1.3.2.1 58-1.2.2.3.1.3.2 60-1.2.2.3.1.3 61-1.2.2.3.1.3.1.1.1.1 63-1.2.2.3.1.3.1.1.1.1 64-1.2.2.3.1.3.1.1.1.2 65-1.2.2.3.1.3.1
Treatment of cells expressing SRC @-@ 1 with epidermal growth factor enhanced the ligand @-@ dependent , progesterone receptor @-@ mediated activation of a target reporter gene . These results identify phosphorylation as a regulatory modification of SRC @-@ 1 and provide a basis upon which to identify signaling pathways that regulate SRC @-@ 1 function and , consequently , modify steroid @/@ nuclear receptor action .
bio-exp_0001.11
CtBPs have also been described to negatively regulate transcriptional activity of the HER3 promoter in breast carcinoma cell lines ( 30 ) .
SDL-AMR-09
2-1.4 4-1 4-1.5 4-1.5.r 5-1.2.r 6-1.2 7-1.2 8-1.2.1.2 9-1.2.1 10-1.2.1.1.r 12-1.2.1.1.1.1.1.1 13-1.2.1.1 13-1.2.1.1.1 13-1.2.1.1.1.r 14-1.3.r 15-1.3.1.2 16-1.3.1.1.1 17-1.3 18-1.3 20-1.5.1.1.1
s
MDA-MB-468
0-1.1.1.2 1-1.1.1.1 3-1.1 5-1.1.1 5-1.1.2 8-1.1.2.1 9-1.1.2.2.r 10-1.1.2.2.1.1 12-1.1.2.2.1.1 14-1.1.3.1.1.1 16-1 17-1.2 18-1.2.2.r 19-1.2.2.3.1 20-1.2.2.3 21-1.2.2.3.r 23-1.2.2.1 24-1.2.2 25-1.2.2.2 27-1.2.2.2.1 29-1.2.2.2.1.2.1.1.1.1 31-1.2.2.2.1.2.1.2.1.1 32-1.2.2.2.1.2
SDL-AMR-09
These findings are similar to what has been observed for C @-@ Raf ( 8 ) and suggest that feedback phosphorylation is a conserved mechanism used to disrupt the Ras @/@ Raf interaction .
bio.mskcc_0001.17
d5
Dephosphorylation of cyclin E by Cdc14 reverses the effects of the mitotic kinases and promotes cyclin E - Cdk2 binding to chromatin .
SDL-AMR-09
0-1.1.1 1-1.1.1.1.r 2-1.1.1.1.1.1 3-1.1.1.1.1.2 4-1.1.1.2.r 5-1.1.1.2.1.1 6-1.1 8-1.1.2 9-1.1.2.1.r 11-1.1.2.1.1 12-1.1.2.1 13-1 14-1.2 15-1.2.2.1.1 16-1.2.2.1.1 18-1.2.2.1.2.1.1 19-1.2.2 20-1.2.2.2.r 21-1.2.2.2.1.1
bio.chicago_2015.18690
serine
151
tyrosine
0-1.1 1-1.1.1.r 2-1.1.1.1.1 4-1.1.1.1.1 6-1.1.1.1.1 7-1.1.2.r 8-1.1.2.1 9-1.1.2 10-1 11-1.2.r 12-1.2.1.2 13-1.2.1 14-1.2.1.1.r 15-1.2.1.1.1.1.1 17-1.2.1.1.1.1.1 18-1.2.1.1 21-1.2.2.3.1 22-1.2.2.3 23-1.2.2 24-1.2.2.2.r 25-1.2.2.2.1 26-1.2.2.2 27-1.2.2.1.r 29-1.2.2.1
Treatment of MDA @-@ MB @-@ 468 with either drug resulted in similar inhibition of ERK1 @/@ 2 phosphorylation , with almost complete elimination of phosphorylated proteins by the combination .
15280923
pmid_1528_0923.109
SDL-AMR-09
V600E
-
V600E
threonine
753
0-1 2-1.1.1.1.1.2.1 3-1.1.1.1.1.2 4-1.1.1.1.1 6-1.1.1.1.1.1.2.1 11-1.1.1.1 13-1.2.1
a_pmid_2488_5690.45
Furthermore , all cells expressed <i> BRAF </i> protein at comparable levels ( Figure <xref ref-type="fig" rid="F1"> 1 </xref>@ C ) .
24885690
SDL-AMR-09
Ras
beta-catenin
JM domain
B-Raf
77
cysteine
PKI166 alone minimally altered the ERK1 @/@ 2 status in the MDA @-@ MB @-@ 231 cells , and U0126 produced some inhibition , while the combination resulted in a substantial reduction , reflecting the effect on cell proliferation and apoptosis .
SDL-AMR-09
pmid_1528_0923.110
0-1.1.1.1.2.1 1-1.1.1.1.3 2-1.1.1.3 3-1.1.1 5-1.1.1.2.1.2.1 7-1.1.1.2.1.2.1 8-1.1.1.2 9-1.1.1.4.r 11-1.1.1.4.2.1 13-1.1.1.4.2.1 15-1.1.1.4.2.1 16-1.1.1.4 18-1.1 19-1.1.2.1.2.1 20-1.1.2 21-1.1.2.2.1 22-1.1.2.2 24-1 26-1.2.1 27-1.2 28-1.2.2.r 30-1.2.2.2 31-1.2.2 33-1.2.3 35-1.2.3.1 36-1.2.3.1.1.r 37-1.2.3.1.1.1.1 38-1.2.3.1.1.1 39-1.2.3.1.1 40-1.2.3.1.1.2
15280923
ERBB3
CTn sequence
mRNA
5F
0-1 2-1.1.1.1 3-1.1.1 5-1.1 6-1.1.2.r 7-1.1.2 7-1.1.2.1 7-1.1.2.1.r 10-1.1.2.2.1
bio.bmtr_0004.26
SDL-AMR-09
Furthermore , this outcome was specific to monoubiquitination at position 147 .
SDL-AMR-09
bio.chicago_2015.17091
A model is proposed in which endosomal Sca and Gp150 promote Notch activation in response to Delta , by regulating acquisition of insensitivity to Delta in a subset of cells .
1-1.1 3-1 6-1.1.1.1.3 7-1.1.1.1.1.1.1 8-1.1.1.1 9-1.1.1.1.2.1.1 10-1.1.1 11-1.1.1.2.1.1.1 12-1.1.1.2 13-1.1.1.2.2.r 14-1.1.1.2.2 15-1.1.1.2.2.1.r 16-1.1.1.2.2.1.1.1 18-1.1.1.3.r 19-1.1.1.3 20-1.1.1.3.1 21-1.1.1.3.1.1.r 22-1.1.1.3.1.1 22-1.1.1.3.1.1.1 22-1.1.1.3.1.1.1.r 23-1.1.1.3.1.1.3.r 24-1.1.1.3.1.1.3 25-1.1.1.3.2.r 27-1.1.1.3.2 28-1.1.1.3.2.1.r 29-1.1.1.3.2.1
e
6A
p
-
SDL-AMR-09
A major advance was our ability to easily generate mUbRas , modified at a single site , in a form suitable for detailed biophysical studies .
bio.bmtr_0004.19
1-1.2 2-1 4-1.1.1 4-1.1.1.r 5-1.1 6-1.1.3.r 7-1.1.3 8-1.1.2 11-1.1.2.2.3 12-1.1.2.2.3.1.r 14-1.1.2.2.3.1.1 15-1.1.2.2.3.1 17-1.1.2.3.r 19-1.1.2.3 20-1.1.2.3.1 21-1.1.2.3.1.1.r 22-1.1.2.3.1.1.2 23-1.1.2.3.1.1.1 24-1.1.2.3.1.1
e2
SDL-AMR-09
bio.mskcc_0001.44
1-1.2 2-1.2.1.r 3-1.2.1 4-1.2.1.1 7-1.1.2.1.1.1 9-1.1.2 10-1.1.2.2.r 11-1.1.2.2.1.1.1 12-1.1.2.2.1.1.2 13-1.1.2.2 15-1.1.1.4.1 15-1.1.1.4.1.1 15-1.1.1.4.1.1.r 17-1.1.1.4 21-1.1.1.1.2.1 23-1.1.1.2.2.1 25-1.1.1 26-1.1.1.3.2.1 27-1.1.1.1.1.1 27-1.1.1.2.1.1 27-1.1.1.3.1.1 29-1.1.1.1.1.1 29-1.1.1.2.1.1 29-1.1.1.3.1.1 32-1 34-1.1
As indicated in Fig. 7A , when PP2A was inhibited with okadaic acid treatment , slower @-@ migrating forms of the V600E , G466A , and D594G B @-@ Raf proteins were found to accumulate .
SDL-AMR-09
<i> BRAF </i> targeting in RKO
24885690
1-1.1.1.1 3-1 4-1.2.r 5-1.2.1.1
a_pmid_2488_5690.33
e3
Dulbecco
50
1
ERK-1
p6
p53
bio.ras_0002.4
SDL-AMR-09
1-1.2 2-1.2.1.r 3-1.2.1.1.1 5-1.2.1.1 6-1.2.1 8-1.3 9-1 10-1.1.r 12-1.1 14-1.1.1.1.1.1 15-1.1.1 16-1.1.1.2.r 17-1.1.1.2.1 19-1.1.1.2.2 19-1.1.1.2.2.r 20-1.1.1.2 23-1.1.2.2 24-1.1.2 27-1.1.2.1
The specificity in Ras - induced signaling is primarily determined by the balance between Ras affinity for each of its effectors and the local concentrations of those effectors .
This interaction leads to the activation of PP5 catalytic activity and to the selective dephosphorylation of the activating serine residue at position 338 , terminating the signal .
SDL-AMR-09
0-1.1.1 1-1.1 2-1 3-1.2.r 5-1.2.1 6-1.2.1.1.r 7-1.2.1.1.1.1.1 8-1.2.1.1.2 9-1.2.1.1 10-1.2 13-1.2.2.2 14-1.2.2 15-1.2.2.1.r 17-1.2.2.1.3 18-1.2.2.1.2.1.1 19-1.2.2.1 22-1.2.2.1.1 24-1.2.3 26-1.2.3.1
bio-kappa_0001.17
PI3K
MDA-MB-468
T677A
PKI166
PKI166
s
3
SDL-AMR-09
bio.chicago_2015.17743
0-1.4 3-1.2 4-1.2.1.r 5-1.2.1.1 6-1.2.1 7-1.2.2 9-1.2.2.1 10-1.2.2 11-1.2.2.2 12-1.2.2.1.1.r 13-1.2.2.1.1.1 14-1.2.2.1.1 15-1.2.2.1.1.2 16-1.2.2.1.1.2.1.r 17-1.2.2.1.1.2.1.1 18-1.2.2.1.1.2.1 19-1.2.2.1.1.2.1.2.1 20-1.2.2.1.1.2.1.2 22-1 23-1.1.r 25-1.1 26-1.1.1.r 27-1.1.1.1.1.1 28-1.1.1 29-1.1.1.2.1.1 30-1.1.1.2.1.2 31-1.1.1.2.1.3 32-1.1.1.2.1.4 36-1.3.1.1.1.1.1.1 37-1.3.1.1.1.1.1.2 38-1.3.1.1.1 39-1.3.1.1.1.2.1 41-1.3.1.1.2.1 43-1.3.1.2.1.1.1.1 44-1.3.1.2.1 45-1.3.1.2.1.2.1.1 47-1.3.1.2.2.1 49-1.3.1.3.1.1.1.1 50-1.3.1 50-1.3.1.2.1 50-1.3.1.3.1 51-1.3.1.3.1.2.1 52-1.3.1.3.2
Currently , a link between MAPK activation and the phosphorylation and activation of transcription factors involved in proliferation and cell growth is established by the finding that MAPK activates p90 ribosomal S6 kinase ( p90RSK ; De Cesare et al. , 1998 ; Frodin and Gammeltoft , 1999 ; Smith et al. 1999 ) .
K-Ras
SDL-AMR-09
The most prevalent oncogenic mutations in Ras ( Gly12 and Gly13 in the G1 box , and Gln61 in the G3 box ) preserve the GTP bound state by inhibiting intrinsic GTPase activity and by interfering with the ability of GAPs .
1-1.1.1.1 2-1.1.1 3-1.1.2 3-1.1.2.1.2.1 4-1.1 5-1.1.1.2.r 6-1.1.1.2.1.1 8-1.1.3.1.1.1 9-1.1.3 10-1.1.3.2.1.1 13-1.1.3.1.2.1.1 14-1.1.3.1.2.1.2 17-1.1.3.3.1.1 20-1.1.3.3.2.1.1 21-1.1.3.3.2.1.2 23-1 25-1.2.1.1.1 26-1.2 28-1.3.r 29-1.3.1 30-1.3.1.2.2 31-1.3.1.2.1.1.1 32-1.3.1.2 33-1.3 35-1.3.2 36-1.3.2.2.r 38-1.3.2.2 39-1.3.2.2.1.r 40-1.3.2.2.1.1.1
bio.ras_0001.9
ERBB3
The tryptic peptide with ubiquitination at Lys147 ( K147 ) was the most frequently observed peptide for both K @-@ Ras and H @-@ Ras , while Lys117 appeared as a secondary major ubiquitination site in H @-@ Ras .
bio.ras_0003.8
SDL-AMR-09
1-1.1.2.1.1.1.1 2-1.1 2-1.1.2 4-1.1.2.2 4-1.1.2.2.3 4-1.1.2.2.3.r 10-1.1.2.r 12-1.1.3.1.1 13-1.1.3.1 14-1.1.3 15-1.1 15-1.1.2 18-1.1.1.1.1.1 20-1.1.1.1.1.1 20-1.1.1.2.1.1 21-1.1.1 22-1.1.1.2.1.1 24-1.1.1.1.1.1 24-1.1.1.2.1.1 26-1 28-1.2 29-1.2.1.r 31-1.2.1.3 32-1.2.1.1 33-1.2.1.2 34-1.2.1 36-1.1.1.2.1.1 38-1.1.1.1.1.1 38-1.1.1.2.1.1
-
2-1.1.1.1.1.1 3-1.1.1.1.1.2 4-1.1.1 4-1.1.1.1.1 4-1.2.1 7-1.1 10-1.1.2 13-1.1.2.1.1.1.1 15-1.1.2.1.2.2 15-1.1.2.1.2.2.r 16-1.1.2.1.2.1.1.1 18-1 20-1.2.1.1 21-1.2 25-1.2.2.r 27-1.2.2.1.1.1 28-1.2.2.1.1 28-1.2.2.1.1.1.1 33-1.2.2.1.1.1.1.1.2 33-1.2.2.1.1.1.1.1.2.1 33-1.2.2.1.1.1.1.1.2.1.r 34-1.2.2.1.1.1.1.1.3.2 35-1.2.2.1.1.1.1.1.1 36-1.1.2.1.2 36-1.2.2 36-1.2.2.1.1.1.1.1 38-1.2.2.1.1.1.1.1.3.1.2.1 39-1.2.2.1.1.1.1.1.3.1.1
SDL-AMR-09
Of the two radioactive peaks , one represented the linker region between the GST and our ASPP2 fragment and the other corresponded to a fragment of the same mass as that containing the second putative phosphorylation site , serine 827 .
bio.bmtr_0005.16
The transition from the inactive to active state requires formation of nucleotide @-@ free Ras through the action of exchange factors .
bmtr_0006.3
1-1.1 4-1.1.2.1 4-1.1.2.1.1 4-1.1.2.1.1.r 6-1.1.1.1 6-1.1.2.1 7-1.1.1 7-1.1.2 8-1 9-1.2 10-1.2.1.r 11-1.2.1.2.1 13-1.2.1 13-1.2.1.2 13-1.2.1.2.r 14-1.2.1.1.1 17-1.2.2 18-1.2.2.1.r 19-1.2.2.1.1 20-1.2.2.1
SDL-AMR-09
5
serine
MEK
GSK-3beta
2H
r
EGFR
Recovery of ERK1 @/@ 2 phosphorylation in the U0126 @-@ treated cells over the period of the growth inhibition assays was not investigated , but the data may also suggest that other signal pathways were contributing to the growth and survival of the cells .
15280923
SDL-AMR-09
0-1.1.2 1-1.1.2.1.r 2-1.1.2.1.1.1.1 4-1.1.2.1.1.1.1 5-1.1.2.1 6-1.1.2.1.2.r 8-1.1.2.1.2.1.1.1.1 10-1.1.2.1.2.1 11-1.1.2.1.2 15-1.1.2.2.r 17-1.1.2.2.1.1 18-1.1.2.2.1 19-1.1.2.2 21-1.1.1 21-1.1.1.r 22-1.1 24-1 26-1.2.1.1 27-1.2 28-1.2.1.3 29-1.2.1 30-1.2.1.2.r 31-1.2.1.2.1.2 32-1.2.1.2.1.1 33-1.2.1.2.1 35-1.2.1.2 36-1.2.1.2.2.r 38-1.2.1.2.2.1 39-1.2.1.2.2 40-1.2.1.2.2.2 41-1.2.1.2.2.1.1.r 43-1.2.1.2.2.1.1
pmid_1528_0923.112
-
bio.bmtr_0003.8
0-1.1.1 1-1.1 2-1 4-1.2.2 5-1.2.1.1.1.1 6-1.2 6-1.2.1 6-1.2.1.r 7-1.2.3 8-1.2.3.1.2 9-1.2.3.1 9-1.2.3.1.1 9-1.2.3.1.1.r 10-1.2.3.1.1.1.r 11-1.2.3.1.1.1.1.1.1 12-1.2.3.1.1.1 13-1.2.3.1.1.1.2.1.1 17-1.2.4.r 18-1.2.4 20-1.2.4.1.1 23-1.2.4.2.1 26-1.3.1 28-1.3.1.1
SDL-AMR-09
Serial deletions identified a minimal HER3 promoter retaining transcriptional response to vemurafenib and AZD6244 , which was located between -@ 401 and -@ 42 bp ( Fig . 5C ) .
24885690
SDL-AMR-09
a_pmid_2488_5690.56
0-1 2-1.1.1.2 3-1.1 5-1.1.1 6-1.1.1.1.r 7-1.1.1.1.1.1.1 8-1.1.1.1.1.1.2 10-1.1.1.1.1.1.2 15-1.1.1.1.1.1.3 16-1.1.1.1 19-1.1.2.1.1.1 26-1.1.1.1.2.2.1.1 27-1.1.1.1.2.3 28-1.1.1.1.2.3 31-1.1.1.1.2.3.1.1.1.1 33-1.1.1.1.2.3.1
However , senescence can be overcome by phosphoinositide 3 @-@ kinase ( PI3K ) / AKT signaling [ @<xref ref-type="bibr" rid="B24"> 24 </xref>@ ] which is hyperactivated in RKO due to a <i> PIK3CA </i> mutation .
interrogative
SDL-AMR-09
bio.bmtr_0002.7
0-1.1 3-1.1.1 5-1 6-1.2.2.1.1.1.1.1 7-1.2.2.1 7-1.2.2.1.1 7-1.2.2.1.1.r 9-1.2.2 10-1.2 11-1.2.1.r 12-1.2.1.1.1.1 13-1.2.1
Mutation of T669 and T677 abrogates MEK inhibitor @-@ induced suppression of ERBB3 Activation
ILK also appears to regulate muscle differentiation by activating Erk , which suppresses transcription factors required for myogenic differentiation ( Huang et al. , 2000 ) .
SDL-AMR-09
bio.chicago_2015.18005
0-1.1.1.1.1 1-1.3 2-1 4-1.1 5-1.1.2.1 6-1.1.2 7-1.1.3.r 8-1.1.3 9-1.1.3.2.1.1 12-1.1.3.2 12-1.1.3.2.2 12-1.1.3.2.2.r 13-1.1.3.2.2.1.1 14-1.1.3.2.2.1 15-1.1.3.2.2.1.2 16-1.1.3.2.2.1.2.1.r 17-1.1.3.2.2.1.2.1.1 18-1.1.3.2.2.1.2.1 20-1.2.1.1.1.1.1 21-1.2.1.1 22-1.2.1.1.2.1 24-1.2.1.2.1
p53
1B
TRX
0-1.1 2-1.4 3-1.3 4-1.2 5-1 7-1.5 8-1.5.1 9-1.5.1 11-1.5.1.1 12-1.5.1.1.1.r 13-1.5.1.1.1.1.1.1.1 15-1.5.1.1.1.1 16-1.5.1.1.1
It is also intrinsically very slow and thus has to be accelerated by GTPase - activating proteins ( GAPs ) .
SDL-AMR-09
bio-kappa_0001.24
0-1 1-1.1 3-1.1 5-1.2 5-1.2.1 5-1.2.1.r
SDL-AMR-09
bio.bmtr_0004.2
Passage 1 @-@ 1 ( Results )
Fanto
As shown in Fig. 5B , immediately after -@ irradiation , the amount of threonine 68 @- phosphorylated Chk2 increased ( lane 2 ) , and prior treatment of cells with caffeine markedly reduced this increase ( lane 4 ) .
SDL-AMR-09
0-1.1.3.r 0-1.2.1.3.r 1-1.3 3-1.4 4-1.4.1 6-1.2.2 7-1.2.2 8-1.2.2 9-1.2.2 10-1.2.2 11-1.2.2 12-1.2.2 13-1.2.2 14-1.2.2 15-1.2.2 16-1.2.2 17-1.2.2 18-1.2.2 19-1.2.2 20-1.2.2 21-1.2.2 22-1.2.2 25-1 26-1.2.1.3 27-1.2.1 28-1.2.1.1.r 29-1.2.1.1 30-1.2.1.2.r 31-1.2.1.2 32-1.2.3 32-1.2.3.r 33-1.2 35-1.2.2 37-1.2.4.1 38-1.2.4.1.1
bel_pmid_1074_4722.88
10744722
ERK12
PLX4032
-
5
ERK1
Tcf-4
-
SDL-AMR-09
Under normal signaling conditions , Ras activation helps mediate these events by recruiting the Raf proteins to the plasma membrane , which induces the release of 14 @-@ 3 @-@ 3 from the N @-@ terminal binding site and facilitates phosphorylation of the Raf kinase domain ( 19 ) .
bio.mskcc_0001.4
1-1.4 2-1.4.1 3-1.4.r 5-1.1.1.1.1 6-1.1 7-1 8-1.2 9-1.2.2.1 10-1.2.2 11-1.3.r 12-1.3 14-1.3.2.1.1 15-1.3.4.1.2 16-1.3.3.r 18-1.3.3.1 19-1.3.3 22-1.3.4 24-1.3.4.1 25-1.3.4.1.1.r 26-1.3.4.1.1.1.1 28-1.3.4.1.1.1.1 30-1.3.4.1.1.1.1 33-1.3.4.1.2.1.1.1 35-1.3.4.1.2.1.1.1 36-1.3.4.1.2.2 37-1.3.4.1.2 39-1.3.5 40-1.3.5.1 41-1.3.5.1.1.r 43-1.3.5.1.1.2 44-1.3.5.1.1.1 45-1.3.5.1.1 47-1.5.1.1.1
10666199
0-1.1.4.r 1-1.1.4.2.1 2-1.1.4.2.1 3-1.1.4.2.1 5-1.1.4.2 6-1.1.4.3 7-1.1.4 8-1.1.4.1.r 9-1.1.4.1.1.1 10-1.1.4.1 12-1.1.1.2.1.1 14-1.1.1.2.1.1 18-1.1.1.1.1.1.1 19-1.1.1.1.1.1.2 20-1.1.1.1 20-1.1.2.2 21-1.1 22-1.1.2 26-1.1.1.1 26-1.1.2.2 28-1.1.3 29-1.1.3.1.r 30-1.1.3.1 31-1.1.3.1.1.r 32-1.1.3.1.1.1.1.1 33-1.1.3.1.1 36-1.2 38-1.2.1.1.1.2 39-1.2.1.1.1 40-1.2.1.1.1.1.r 41-1.2.1.1.1.1.1.1 42-1.2.1.1.1.1.1.2 43-1.2.1.1 45-1.2.1.1.2.1.1 46-1.2.1.1.2.1 47-1.2.1.1.2 52-1.2.1.1.2.2 54-1.2.1 55-1.2.1.2.r 56-1.2.1.2.2.1.1.1 58-1.2.1.2.2.1.1.1 60-1.2.1.2.2 61-1.2.1.2.1.1 62-1.2.1.2 63-1.2.1.2.3 64-1.2.1.2.3.1.1.1 66-1.2.1.2.3.1.1.1
SDL-AMR-09
During IL @-@ 6 @-@ induced macrophage differentiation of M1 cells , IL @-@ 6 down @-@ regulated cyclin D1 expression and induced p19( INK4D ) expression , leading to reduction in cdk4 activities . In contrast , sustained expression of cyclin D1 and a significantly lesser amount of p19( INK4D ) induction were observed in IL @-@ 6 @-@ treated M1 cells overexpressing GATA @-@ 1 .
bel_pmid_1066_6199.38222
p53
EGFP
C-terminus
serine
2
6
SDL-AMR-09
Importantly , we show that wild @-@ type B @-@ RAF can also activate C @-@ RAF .
bio.bel_0002.3
0-1.3 2-1.1 3-1 4-1.2.r 5-1.2.1.1.2 7-1.2.1.1.2 8-1.2.1.1.1.1 10-1.2.1.1.1.1 10-1.2.1.2.1.1 11-1.2 12-1.2.1.3 13-1.2.1 14-1.2.1.2.1.1 16-1.2.1.1.1.1 16-1.2.1.2.1.1
Erk
ASPP2
stauro
beta-catenin
GEF
Cancer
cancer
SDL-AMR-09
0-1.3.1.1 2-1.1 2-1.1.r 3-1 5-1.2.3.1.1 10-1.2 11-1.2.3.1.1 13-1.2.3.1.1
CKI did not phosphorylate GSK3 beta , B56 alpha , or beta @-@ TrCP .
bio.chicago_2015.17707
f
SDL-AMR-09
bio.mskcc_0001.42
Interestingly , when the S729A mutation was introduced into the FBm mutant , binding to C @-@ Raf was abolished ( Fig . 6A ) , indicating that the increased heterodimerization observed when the feedback sites are mutated is still dependent on 14 @-@ 3 @-@ 3 binding .
0-1.4 0-1.4.r 2-1.3.r 4-1.3.1.1 5-1.3.1 5-1.3.2 5-1.3.2.3 5-1.3.2.3.r 7-1.3 8-1.3.2.4.2.1.r 11-1.3.1 11-1.3.2 11-1.3.2.3 11-1.3.2.3.r 13-1.1 14-1.1.1.r 15-1.1.1.2.1 17-1.1.1.2.1 17-1.3.2.2.1 19-1 21-1.2.1 23-1.2.1.1 26-1.5 27-1.5.1.r 29-1.5.1.1.1 30-1.5.1.1 31-1.5.1.1.2 32-1.5.1.1.2.1.r 34-1.3.2.4.2.1 34-1.5.1.1.2.1.1.1 35-1.3.2.4.2 35-1.5.1.1.2.1.1 37-1.5.1.1.2.1 39-1.5.1.3 40-1.5.1 41-1.5.1.2.r 42-1.5.1.2.1.2.1 44-1.5.1.2.1.2.1 46-1.5.1.2.1.2.1 47-1.5.1.2
1m
However , the withdrawal of serum resulted in the inhibition of cell growth of the wild @-@ type cells RBW @-@ 1 ( Figure <xref ref-type="fig" rid="F2"> 2 </xref>@ B and C ) .
a_pmid_2488_5690.51
0-1 3-1.1.1 4-1.1.1.1.r 5-1.1.1.1 6-1.1 7-1.1.2.r 9-1.1.2 10-1.1.2.1.r 11-1.1.2.1.1 12-1.1.2.1 15-1.1.2.1.1.2 17-1.1.2.1.1.2 18-1.1.2.1.1 19-1.1.2.1.1.1.1 21-1.1.2.1.1.1.1 23-1.2.1.1 23-1.2.1.2 28-1.2.1
24885690
SDL-AMR-09
At the nucleus , PKC betaII directly phosphorylates the nuclear envelope polypeptide lamin B at sites involved in mitotic nuclear lamina disassembly ( 8 @-@ 10 ) .
SDL-AMR-09
2-1.4 4-1.2.1.1 5-1.2.1.2 6-1.3 6-1.3.r 7-1 9-1.1.2.1 10-1.1.2 12-1.1.1.1 13-1.1.1.2 14-1.5.r 15-1.5 16-1.5.1 18-1.5.1.1.2.2 19-1.5.1.1.2.1 20-1.5.1.1.2 23-1.6.1.1.1.1 25-1.6.1.1.1.2
bio.chicago_2015.17227
AZD6244
Ras
SDL-AMR-09
pmid_1528_0923.81
Initial studies used a dose range of 0.1 @–@ 5.0 <i> μ </i>@ <sc> M </sc> ( data not shown ) , and the results of treating cells with 0.5 and 5.0 <i> μ </i>@ <sc> M </sc> are shown in <xref ref-type="table" rid="tbl1"> Table 1 </xref>@ .
15280923
0-1.1.1.1 1-1.1.1 2-1.1 4-1.1.2.1 5-1.1.2 6-1.1.2.2.r 7-1.1.2.2.1 9-1.1.2.3.1 17-1.1.3.2 18-1.1.3.1 18-1.1.3.1.r 19-1.1.3 22-1 24-1.2.1 24-1.2.1.1 24-1.2.1.1.r 25-1.2.1.1.1.r 26-1.2.1.1.1 27-1.2.1.1.1.1 28-1.2.1.1.1.2.r 29-1.2.1.1.1.2.1.1 30-1.2.1.1.1.2 31-1.2.1.1.1.2.2 39-1.2 42-1.2.2 43-1.2.2.1
MAP kinase
ASPP2
4
m
oncwt-
K-Ras
Raf
1
0-1.1.1 4-1.4 5-1 6-1.2.r 7-1.2 8-1.2.1.r 9-1.2.1.1.1.1 10-1.2.1 12-1.3.1 13-1.3 15-1.3.2 16-1.3.2.1.3 19-1.3.2.1.1.1.1 22-1.3.2.1.1.2.1 23-1.3.2.1.1.2 24-1.3.2.1.1.2.2.2 25-1.3.2.1.1.2.2 26-1.3.2.1.1.2.2.1.r 27-1.3.2.1.1.2.2.1.1 28-1.3.2.1.1.2.2.1 30-1.5.1.1.1
SDL-AMR-09
bio.bmtr_0003.18
These corepressors have been previously linked to inhibition of HER3 transcription through promoter regions that show overlapping occupancy with ZNF217 , a transcription factor also involved in HER3 regulation ( 30 ) .
histidine
C-Raf
S1D
bmtr_0007.11
1-1.2.1.2.1.1.2 3-1 3-1.1.1 4-1.1 6-1.2.1.1.1.1.1 6-1.2.1.2.1.1.1.1 8-1 10-1.2.1.1 12-1.2.1.1.1.1.1 12-1.2.1.2.1.1.1.1 13-1.2.1 16-1.2.1.2 18-1.2.1.2.1 20-1.2.1.2.1.1.2 22-1.2.1.1.1.1.1 22-1.2.1.2.1.1.1.1
SDL-AMR-09
The phospho @-@ specific antibody for ASPP2 is specific as knockdown of ASPP2 resulted in a lack of detection of phospho @-@ ASPP2 .
bio.bmtr_0001.2
We utilized an unbiased mass spectrometry @-@ based approach to identify ubiquitination sites of Ras .
0-1.1 1-1 3-1.2.2 3-1.2.2.1 3-1.2.2.1.r 4-1.2.1.1.1 5-1.2.1.1 7-1.2.1 8-1.2 10-1.3 11-1.3.2.2 12-1.3.2 13-1.3.2.1.r 14-1.3.2.1.1.1
SDL-AMR-09
GST-RBD
GTP
serine
216
bio-kappa_0001.14
SDL-AMR-09
Since the sites have been described alternatively as negative regulatory or activating , the significance of these dephosphorylation events for Raf activation is unclear .
2-1.2.1 5-1.2 6-1.2.3 6-1.2.3.r 7-1.2.2.r 8-1.2.2.1 9-1.2.2.1 10-1.2.2 11-1.2.2.2 14-1.3 15-1.3.2.r 16-1.3.2.1 17-1.3.2 19-1.3.1.r 20-1.3.1.1.1.1 21-1.3.1 23-1 23-1.1 23-1.1.r
beta-galactosidase
BRAF
1
GTP
p53
2G
0-1.1 1-1.1.1.r 2-1.1.1 2-1.1.1.2 2-1.1.1.2.r 3-1.1.1.1.1 4-1 5-1.2.r 6-1.2.1.2.1.1 8-1.2.1.2.1.1 9-1.2.1 9-1.2.1.1 9-1.2.1.1.r 11-1.2.2.1 12-1.2.2 14-1.2 16-1.2.3.3 18-1.2.3 19-1.2.3.1.r 20-1.2.3.1 21-1.2.3.1 22-1.2.3.1
bel_pmid_1064_8414.21216
SDL-AMR-09
10648414
Overexpression of mutant FGFR3 resulted in IL @-@ 6 independence , decreased apoptosis , and an enhanced proliferative response to IL @-@ 6 .
401
threonine
B-Raf
B-Raf
K375M
c2
bio.bmtr_0002.3
0-1.1 1-1 2-1.2.2 3-1.2.1 4-1.2 6-1.3 8-1.3.2 9-1.3.2.1.r 10-1.3.2.1.1.1 11-1.3.2.2.r 12-1.3.2.2 13-1.3.2.2.1.r 14-1.3.2.2.1.3 15-1.3.2.2.1.2.1.1 16-1.3.2.2.1.2.1.2 17-1.3.2.2.1.1.1.1 18-1.3.2.2.1 21-1.3.2.3.1.1.3.1.1.1 23-1.3.2.3.1.1.3 24-1.3.2.3 25-1.3.2.3.2.1.3.1.1.1 27-1.3.2.3.2.1.3 28-1.3.2.3.1.1.2.1 28-1.3.2.3.2.1.2.1 29-1.3.2.3.1 29-1.3.2.3.2
SDL-AMR-09
We used tandem mass spectrometry to measure the effects of AZD6244 on phosphorylation of this JM domain threonine residue in both EGFR @-@ mutant and HER2 @- amplified cancer models .
p2
e
28
30
ASPP2
Bonni
bio.chicago_2015.19008
0-1.2 1-1.2 4-1.1.1.1 5-1.1.1 6-1.1.1.2.r 7-1.1.1.2.1.1 8-1.1.1.3.r 9-1.1.1.3.1.2.1.1 11-1.1.1.3.1 11-1.1.1.3.1.1 11-1.1.1.3.1.1.r 12-1.1.1.3 13-1.1.1.3.2.r 14-1.1.1.3.2.1.1 16-1.1.1.1.1.1.1.1.1.1 17-1.1.1.1.1.1.1 18-1.1.1.1.1.1.1.2.1 20-1.1.1.1.1.1.2.1 22-1 24-1.1 25-1.1.2.r 27-1.1.2 28-1.1.2.2.r 29-1.1.2.2.1 31-1.1.2.2 32-1.1.2.2.2.1 33-1.1.2.2.2 34-1.1.2.2.2.2.r 35-1.1.2.2.2.2.1.1.1 36-1.1.2.2.2.2
SDL-AMR-09
For instance , the proposed role of Grb2 in clathrin @-@ independent endocytosis of EGFR ( Yamazaki et al. , 2002 ) may be related to the ability of Grb2 to mediate EGFR signaling to actin cytoskeleton
RAF265
V600E
bio-kappa_0001.4
1-1.1.2.1.1 3-1.1.2.1.1 5-1.1.1 6-1.1 6-1.3.1.2.2.1 6-1.3.1.2.2.2 8-1.2 9-1 10-1.3 11-1.3 13-1.3.1.1.2 14-1.3.1.1 17-1.3.1.1.1 19-1.3.1.1.1 20-1.3.1.1.1.2.1 22-1.3.1 23-1.3.1.r 25-1.3.1.2 26-1.3.1.2.1.r 27-1.3.1.2.1.1 31-1.3.1.2.2.1.1 35-1.4.1 36-1.4.1.1
SDL-AMR-09
In B @-@ Raf , this motif is negatively charged due to the constitutive phosphorylation of Ser446 and @/@ or 447 , and to the presence of two aspartates at position 448 @/@ 9 ( Fig. 2A ) .
66
1
EGF receptor
SDL-AMR-09
0-1.1.1.2 4-1.1.1 5-1.1 7-1.1.2 8-1.1.2.1.r 9-1.1.2.1.1.1 10-1.1.2.2.r 11-1.1.2.2.1.1 13-1 16-1.2.2.1 17-1.2.2.1 18-1.2.2 19-1.2.2
This switch - ON process involves the exchange of GDP for GTP , and is , at least in principle , reversible .
bio-kappa_0001.22
15280923
<sec-title level="2"> PKI166 inhibition of breast cancer cell proliferation </sec-title>
1-1.1.1.1 2-1 3-1.2.r 4-1.2.1.1.2.1 5-1.2.1.1.2.2 6-1.2.1 7-1.2
SDL-AMR-09
pmid_1528_0923.79
cyclin E
BRAF
G12V
RKO
0-1.1 0-1.1.1 0-1.1.1.r 1-1.2.2.1.1 2-1.2 3-1.2 5-1.2.1.1.1.1.1 6-1.2.1.1 7-1.2.1 9-1.2.1.2 10-1.2.1.3 11-1.2.1.3.1.r 12-1.2.1.3.1.1.1.1 13-1.2.1.3.1 14-1.2.3.r 16-1.2.3.1.1 17-1.2.3.2.1.1 18-1.2.3.2.2 19-1.2.3 19-1.2.3.2 19-1.2.3.2.r 21-1.3.4 23-1.3.4.2.2 24-1.3.4.2 25-1.3.4.2.1.r 26-1.3.4.2.1 28-1.3.1 29-1.3 30-1.3.2.1.1.1 31-1.3.2 32-1.3.2.2.r 34-1.3.2.2 35-1.3.2.2.1.r 36-1.3.2.2.1.1.1.1 37-1.3.2.2.1 38-1.3.2.2.1 39-1.3.3.r 40-1.3.3.1 41-1.3.3
SDL-AMR-09
Results CD72 negatively regulates both ERK activation and Ca2+ mobilization induced by BCR ligation in the K46^mk B lymphoma cells To investigate the signaling function of CD72 , we assessed CD72 expression on the surface of B cell lines by flow cytometry .
bel_pmid_1064_0734.39804
10640734
PLX4032
B-Raf
0.5
PDTC
-
bio.bmtr_0003.15
Finally , CtBP1 and CtBP2 chromatin immunoprecipitation assays showed decreased binding to the HER3 promoter after treatment with PLX4032 ( Fig . 5F ) .
0-1.1 0-1.1.r 2-1.2.1.1.1.1.1 3-1.2.1.1 4-1.2.1.1.2.1.1 5-1.2.1.2 6-1.2.1 7-1.2 8-1 9-1.3.2 10-1.3 11-1.3.1.r 13-1.3.1.1.1.1.1 14-1.3.1 14-1.3.1.1 14-1.3.1.1.r 15-1.3.2.1 16-1.3.2.1.1 17-1.3.2.1.1.1.r 18-1.3.2.1.1.1.1.1 20-1.4.1 22-1.4.1.1
SDL-AMR-09
5C
-
B
SDL-AMR-09
0-1.1.2.2.1 2-1.1.2 2-1.1.2.2 2-1.1.2.2.r 3-1.1.2.1.1 3-1.2.1.2.2.1.1 5-1.1.1 5-1.1.1.r 6-1.1 7-1.1.3.1.1.1.1 9-1.1.3.1 10-1.1.3 12-1 13-1.1.1 13-1.2.4.1 16-1.2.1 18-1.2.1.1.2.1.1 19-1.2.1.2.r 20-1.2.1.2.1.4 21-1.2.1.2.1.4 22-1.2.1.2.1.4 23-1.2.1.2.1.3.1.1.1 25-1.2.1.2 26-1.2.1.2.2.2.1.1.1 28-1.2.1.2.1.3 28-1.2.1.2.2.2 29-1.2.1.2.1.2 30-1.2.1.2.1.1.1 37-1.2 38-1.2.2 41-1.2.3.1.1 42-1.1 42-1.2.3 42-1.2.3.1 42-1.2.3.1.r 44-1.3.1 45-1.3.1.1
Full @-@ length Axin did not activate TCF @-@ dependent transcription , but unexpectedly , the introduction of L521P into full @-@ length Myc @- or Flag @-@ tagged murine Axin [ mFlagAx-( 1 @-@ 956 )] transformed it into a transcriptional activator ( Figure 5D ) .
bio.chicago_2015.18510
449
GSK3 beta
c2
GST-RBD
U0126
-
-
ERBB
bio.mskcc_0001.13
SDL-AMR-09
0-1.3 2-1.1.1.2 3-1.1.1 3-1.1.1.1 3-1.1.1.1.r 4-1.1 5-1.1.2.r 6-1.1.2.1.1.1 8-1.1.2 9-1.1.2.2.r 11-1.1.2.2.2 12-1.1.2.2 13-1.1.2.2.1.r 14-1.1.2.2.1.1.1 16-1.1.2.2.1.1.1 17-1 19-1.2 20-1.2.2.r 22-1.2.2 25-1.2.2.1.1 26-1.2.2.1 27-1.2.2.1.2.1.1.1 28-1.2.2.1.2
Together , these findings indicate that Pin1 is needed for the efficient dephosphorylation of B @-@ Raf and are consistent with the model that S/TP phosphorylation inhibits Raf signaling .
bio.ras_0003.3
His - ubiquitinated proteins were purified by Co2+ metal affinity chromatography in 8M urea denaturing conditions .
2-1.1.1 3-1.1 5-1 9-1.2.1 10-1.2 13-1.2.2.2.1.1 14-1.2.2 15-1.2.2.r
SDL-AMR-09
PAF
i2
-
0-1.1.1 1-1.1 2-1.1.2.1.1 3-1.1.3.r 4-1.1.3.1.1 5-1.1.3 6-1 7-1.2 9-1.2.2 9-1.2.3 12-1.2.2.1.2 12-1.2.2.1.2.1 12-1.2.2.1.2.1.r 14-1.2.3.1.2 14-1.2.3.1.2.1 14-1.2.3.1.2.1.r 15-1.2.2.1 15-1.2.3.1 17-1.1.2.1.1 19-1.2.2.2 19-1.2.3.2 20-1.2.2.2.1.r 21-1.2.2.2.1.1.1
We immunoprecipitated Ras from HEK293T cells and compared the sensitivity of the monoubiquitinated and unmodified fractions of Ras to regulation by GAP .
bio.bmtr_0004.13
SDL-AMR-09
HER2
L521P
SDL-AMR-09
We show here that ASPP2 is phosphorylated by the RAS/Raf/MAPK pathway and that this phosphorylation leads to its increased translocation to the cytosol @/@ nucleus and increased binding to p53 , providing an explanation of how RAS can activate p53 pro @-@ apoptotic functions ( Figure 5 ) .
bio.bmtr_0005.22
0-1.1 1-1 2-1.3 3-1.2.r 4-1.2.1.1.1 6-1.2 9-1.2.2.1.1 10-1.2.2 14-1.2 15-1.2.3 18-1.2.3.1.1 19-1.2.3.1.1.1 20-1.2.3.1.1.1.2.r 22-1.2.3.1.1.1.2.1 23-1.2.3.1.1.1.2 24-1.2.3.1.1.1.2.2 25-1.2.3.1 26-1.2.3.1.1 26-1.2.3.1.2 27-1.2.3.1.2.1 28-1.2.3.1.2.1.2.r 29-1.2.3.1.2.1.2.1.1 33-1.2.4 36-1.2.4.1.1.1.1.1 37-1.2.4.1 38-1.2.4.1.1 39-1.2.4.1.1.2.1 40-1.2.4.1.1.2.2.1 42-1.2.4.1.1.2.2 43-1.2.4.1.1.2 45-1.2.5.1 46-1.2.5.1.1
32
SDL-AMR-09
When compared to p38 SAPK , MAPK1 was clearly able to phosphorylate the ASPP2 fragment in vitro ( Figure 1B , left and middle panels ) .
1-1.3.r 3-1.3.1.2.1.1 4-1.3.1.2.1.2 6-1.1.2.1.1 8-1.2 9-1 9-1.3 11-1.1 11-1.3.1 13-1.1.1.1.1.1 15-1.1.3 16-1.1.3 18-1.4.1.3 19-1.4.1.3.1 21-1.4.1.1.1 22-1.4.1 23-1.4.1.2.1 24-1.4.1.1 24-1.4.1.2
bio.bmtr_0005.11
SDL-AMR-09
bio.bmtr_0001.8
Tandem mass spectrometric analysis of tryptic fragments from the bands migrating at the positions expected for mono @- and di @-@ ubiquitinated Ras revealed ubiquitination at Lys residues 104 and 147 of K @-@ Ras , and Lys residues 117 , 147 and 170 for H @-@ Ras ( fig . S1C ) .
0-1.1.2.2 1-1.1.2.1 2-1.1.2 3-1.1 4-1.1.1.r 5-1.1.1.1.1.1.1 7-1.1.1.2.r 9-1.1.1.2 10-1.1.1.2.1 11-1.1.1.2.1.1.1 13-1.1.1.2.1.1 14-1.1.1.2.1.1.1.2 16-1.1.1.2.1.1.1.1.2.1.1 16-1.1.1.2.1.1.1.1.2.1.r 19-1.1.1.2.1.1.1.1.2.1.2 19-1.1.1.2.1.1.1.1.2.1.r 21-1.1.1.2.1.1.1.1.2 21-1.2 22-1.1.1.2.1.1.1.1.1.1 23-1 24-1.1.1.2.1.1.1.1.2 24-1.2 25-1.1.1.2.1.1.1 25-1.2.1.r 26-1.2.1.1.1.1.2.1 26-1.2.1.1.2.1.2.1 26-1.2.1.2.1.1.2.1 26-1.2.1.2.2.1.2.1 27-1.2.1.1.1 27-1.2.1.1.2 27-1.2.1.2.1 27-1.2.1.2.2 28-1.2.1.1.1.1.1 29-1.2.1.1 30-1.2.1.1.2.1.1 32-1.2.1.1.3.1.1 34-1.2.1.1.3.1.1 36-1.2.1 36-1.2.1.1 36-1.2.1.1.r 36-1.2.1.2 37-1.2.1.1.2.1.2.1 37-1.2.1.2.1.1.2.1 37-1.2.1.2.2.1.2.1 37-1.2.1.2.3.1.2.1 38-1.2.1.1.2 38-1.2.1.2.1 38-1.2.1.2.2 38-1.2.1.2.3 39-1.2.1.2.1.1.1 41-1.2.1.2.2.1.1 43-1.2.1.2.3.1.1 44-1.2.1.2.r 45-1.2.1.2.4.1.1 47-1.2.1.2.4.1.1 51-1.3.1.1
B-Raf
HER3
U0126
2+
EGFR
bio.chicago_2015.18319
0-1.1.1.1.1.1 2-1.1.3 3-1.1.1 4-1.1.1.2.r 5-1.1.1.2.1.1 8-1.1.4.1.1.1 9-1.1 10-1.1.2 13-1.1.2.1 15-1.1.4 17-1.1.4.1.1.1 19-1.1.4.1.1.1 21-1.1.4.2.1.1.1 24-1.1 26-1.2.1 27-1.2 29-1.2.2 30-1.2.2.1.r 31-1.2.2.1 33-1.1.4.1.1.1 35-1.1.4.1.1.1 37-1.2.3.1.1.1.1 39-1.2.3.1.1.1.2
Axin is also phosphorylated by GSK @-@ 3 beta and stabilized by its phosphorylation in contrast to beta @-@ catenin ( 22 ) , and the phosphorylation increases the binding of Axin to beta @-@ catenin ( 23 , 24 ) .
SDL-AMR-09
SDL-AMR-09
For some of these transcription factors , the domain that interacts with Groucho is mapped to a short peptide motif .
bio.chicago_2015.17615
1-1.3.2 2-1.3.2.r 3-1.3.3 4-1.3.1 5-1.3 8-1.1 10-1.1.1 11-1.1.1.1.r 12-1.1.1.1.1.1 14-1 15-1.2.r 17-1.2.1.1 18-1.2.1 19-1.2
RKO
5
CKI
SDL-AMR-09
bio.bmtr_0005.9
0-1.1.1 1-1 2-1.1 3-1.1.2.1 3-1.1.2.1.r 4-1.1.2.2.1.1.1.1 5-1.1.2.2.1 6-1.1.2 7-1.1.2.2 8-1.1.2.2.2.1.1.1 9-1.1.2.2.2
We thus tested whether RAS activation may regulate ASPP2 phosphorylation .
2
693
SDL-AMR-09
0-1.3 1-1.1 2-1 3-1.2.r 4-1.2.1 4-1.2.1.1 4-1.2.1.1.r 5-1.2 7-1.2.2 8-1.2.2.1.r 9-1.2.2.1.1.1 10-1.2.2.2.r 11-1.2.2.2.1.1.1.1 13-1.2.2.2.1 14-1.2.2.2
Here we show that monoubiquitination decreases the sensitivity of Ras to GAP @-@ mediated hydrolysis .
bio.bmtr_0004.18
homeodomain
3A
GTP
HER2
tyrosine kinase Fyn
bel_pmid_1066_6199.2154
overexpressions of cyclin D1 or bcl @-@ 2 inhibited only differentiation or apoptosis , respectively
0-1.1 1-1.1.1.r 2-1.1.1.1.1.1 3-1.1.1.1.1.2 4-1.1.1 5-1.1.1.2.1.1 7-1.1.1.2.1.1 8-1 9-1.3 10-1.2.1 11-1.2 12-1.2.2 14-1.4 14-1.4.r
10666199
SDL-AMR-09
C-Raf
B
bio.chicago_2015.18750
1-1.1.3.5 2-1.1.3.4 3-1.1.3.3 4-1.1.3.1.1.1 5-1.1.3.1.1.2 7-1.1.3.2.1.1 8-1.1.3 11-1.1.2.1 13-1.1.3.r 13-1.1.4.r 15-1.1.4.1.1.r 16-1.1.4.2 17-1.1.4 18-1.1.4.1.r 20-1.1.4.1.1.3 21-1.1.4.1.1.2 22-1.1.4.1.1 22-1.2.1.1.1 23-1.1.4.1.1.1.1 25-1.1.4.1.1.1.1 26-1.1.4.1.1.r 28-1.1.4.1 31-1.1.3.2.1.1 32-1.1.3.1 32-1.1.3.2 32-1.1.4.1.2 32-1.2.1.1.2 33-1.1.4.1.2.1.1 35-1.1.4.3.1.1.1.1.1.1 35-1.2.2.1.1.1.1.1.1 36-1.1.4.3.1 36-1.1.4.3.1.1.1 36-1.1.4.3.1.2.1 36-1.2.2.1 36-1.2.2.1.1.1 36-1.2.2.1.2.1 37-1.1.3.4 37-1.1.4.3.1.1.1.2.1 37-1.1.4.3.1.2.1.2.1 37-1.2.2.1.1.1.2.1 37-1.2.2.1.2.1.2.1 39-1.1.4.3.1.1.2.1 41-1.1.4.3.1.2.1.1.1.1 41-1.2.2.1.2.1.1.1.1 42-1.1.4.3.1 42-1.1.4.3.1.1.1 42-1.1.4.3.1.2.1 42-1.2.2.1 42-1.2.2.1.1.1 42-1.2.2.1.2.1 43-1.1.3.4 43-1.1.4.3.1.1.1.2.1 43-1.1.4.3.1.2.1.2.1 43-1.2.2.1.1.1.2.1 43-1.2.2.1.2.1.2.1 45-1.1.4.3.1.1.2.1 49-1.2.3.1 50-1.2.3 53-1.2.1.1.3 54-1.2.1.1 55-1.1.3.1.r 56-1.2.1.1.1.1.1 58-1.2.1.1.1.1.1 59-1.1.4.3.1 59-1.1.4.3.1.1.1 59-1.1.4.3.1.2.1 60-1.1.4.1.2.1.1 62-1.2 64-1.2.1 66-1.2.1.2 69-1.2.1.1.2.1.1 70-1.2.1.2.2.r 71-1.2.1.2.2.3 71-1.2.1.2.2.3.r 72-1.2.1.2.2.2.1 72-1.2.1.2.2.2.1.1 72-1.2.1.2.2.2.1.1.r 74-1.2.1.2.2.2 75-1.2.1.2.2.1 76-1.2.1.2.2 78-1.2.2.1.1.1.1.1.1 79-1.2.2.1 79-1.2.2.1.1.1 79-1.2.2.1.2.1 80-1.2.2.1.1.1.2.1 80-1.2.2.1.2.1.2.1 82-1.2.2.1.2.2 84-1.2.2.1.2.1.1.1.1 85-1.2.2.1 85-1.2.2.1.1.1 85-1.2.2.1.2.1 86-1.2.2.1.1.1.2.1 86-1.2.2.1.2.1.2.1 88-1.2.1.3.1.3.1.3.2.1 91-1.2.1.3.2 97-1.2.1.3.1.1.1.1.1 98-1.2.1.3.1.1 99-1.2.1.3.1.1.2.1.1 100-1.2.1.3.1 102-1.2.1.3.1.2.2.1.1.1 103-1.2.1.3.1.2.2 104-1.2.1.3.1.2 106-1.2.1.3.1.2.1.1.1 107-1.2.1.3.1.1.1 107-1.2.1.3.1.1.2 107-1.2.1.3.1.2.1 109-1.2.1.3.1.3.1.1.1.1.1.1 110-1.2.1.3.1.3.1.1.1 111-1.2.1.3.1.3.1.1.1.2.1 113-1.2.1.3.1.3.1.1.2.1 115-1.2.1.3.1.3.1.2.1.1.1.1 116-1.2.1.3.1.3.1.2.1 117-1.2.1.3.1.3.1.2.1.2.1.1 119-1.2.1.3.1.3.1.2.2.1 121-1.2.1.3.1.3.1.3.1.1.1.1 122-1.2.1.3.1.3.1.3.1 123-1.2.1.3.1.3.1.3.1.2.1.1 125-1.2.1.3.1.3.1.3.2.1
SDL-AMR-09
The only other known zinc finger @-@ homeodomain cooperation is in Drosophila , where it was recently shown that the orphan nuclear receptor alphaFtz @-@ F1 is a cofactor for the homeodomain protein Ftz ( Guichet et al. , 1997 ; Yu et al. , 1997 ) ; in this case , the physical association between alphaFtz @-@ F1 and Ftz is thought to enhance the binding of the Ftz to its lower @-@ affinity target sequences ( Guichet et al. , 1997 ; Yu et al. , 1997 ) , much in the same way that Extradenticle and Pbx modulate the DNA binding activity of Hox proteins ( Phelan et al. , 1995 ; Lu and Kamps , 1996 ; Peltenburg and Murre , 1997 ) .
bio.bel_0002.4
The homologous site on B @-@ Raf , S445 , is constitutively phosphorylated , accounting for the higher basal activity of B @-@ Raf .
SDL-AMR-09
4-1.1.3.1.1 6-1.1.3.1.1 11-1.2 12-1 14-1.3 15-1.3.1.r 17-1.3.1.3 17-1.3.1.3.1 17-1.3.1.3.1.r 18-1.3.1.2 19-1.3.1 20-1.3.1.1.r 21-1.3.1.1 22-1.3.1.1 23-1.3.1.1
histidine
MAPK
MEK1
B-Raf
bio.bmtr_0003.6
SDL-AMR-09
1-1.1.1 2-1.1.1.1.r 4-1.1.1.1.1.1.1.1 5-1.1.1.1 5-1.1.1.1.1 5-1.1.1.1.1.r 6-1.1.1.2.r 7-1.1.1.2.1.2 8-1.1.1.2.1.1.1 10-1.1.1.2.2.1.1 10-1.1.1.2.3.1.1 11-1.1.1.1.1.1 16-1.1.2 17-1.1 19-1 20-1.2.3 21-1.2 22-1.2.2.r 24-1.2.2.1.r 26-1.2.2.1 28-1.1.1.2.3.2 28-1.2.2.1.1.1.1 30-1.3.1 32-1.3.1.1
The effects of the MEK inhibitor on total HER2 , HER3 protein and on pHER3 were dose dependent , and inversely associated with the degree of inhibition of pERK ( Fig . 5B ) .
O'Connor
a
ERK12
22
FGFR3
SDL-AMR-09
24885690
Genetic targeting of mutant <i> BRAF </i> resulted in restoration of sensitivity to serum starvation @-@ induced apoptosis and efficiently inhibited cell proliferation in the absence of growth factors .
a_pmid_2488_5690.10
1-1.1.1 2-1.1.1.1.r 3-1.1.1.1 3-1.1.1.1.3 3-1.1.1.1.3.r 5-1.1.1.1.2.1 7-1.1 8-1.1.2.r 9-1.1.2 10-1.1.2.1.r 11-1.1.2.1 12-1.1.2.1.1.r 13-1.1.2.1.1.1.1.1 14-1.1.2.1.1.1.1 16-1.1.2.1.1.1 17-1.1.2.1.1 18-1 19-1.2.3 20-1.2 21-1.2.2.1 22-1.2.2 23-1.2.2.2.r 25-1.2.2.2 26-1.2.2.2.1.r 27-1.2.2.2.1 28-1.2.2.2.1
ASPP2
GTPase
e2
bio.mskcc_0001.52
As has been observed for C @-@ Raf , we find that the hyperphosphorylated B @-@ Raf protein is subsequently dephosphorylated in a manner requiring the activities of the PP2A phosphatase and Pin1 prolyl @-@ isomerase , indicating that the feedback phosphorylation @/@ dephosphorylation cycle is a conserved regulatory mechanism for the Raf proteins .
SDL-AMR-09
0-1.2.5.r 3-1.2.2.1.2 5-1.2.2.1.1.1.1 7-1.2.4.1.1.1.1.1 9-1.1 10-1 13-1.2.1.2 13-1.2.2.1.1.2 14-1.2.1.1.1 16-1.2.4.1.1.1.1.1 17-1.2.4.1.1.1 18-1.2.4.1.3.r 19-1.2.5 19-1.2.5.r 20-1.2 20-1.2.2.1 23-1.2.3.r 24-1.2.3 26-1.2.3.2.1 26-1.2.3.2.2 27-1.2.3.2.1.1.r 29-1.2.3.2.1.1.1.1 30-1.2.3.2.1.1 31-1.2.3.2 32-1.2.3.2.2.1.1.1 33-1.2.3.2.2.1 35-1.2.3.2.2.1 37-1.2.4 40-1.2.4.1.3.3 41-1.2.4.1.3.1 43-1.2.4.1.3.2 44-1.2.4.1.3 45-1.2.4.1.3.r 47-1.2.4.1.2 48-1.2.4.1.1 49-1.2.4.1 52-1.2.4.1.1.1.1.1 53-1.2.4.1.1.1
p3
bio.bmtr_0005.15
The fractions representing these radioactive peaks were analysed by mass spectrometry .
1-1.1 2-1.1.1 3-1.1.1.1.2 4-1.1.1.1.1 5-1.1.1.1 7-1 8-1.2.r 9-1.2.1 10-1.2
SDL-AMR-09
cancer
Cancer
SDL-AMR-09
Inhibition of SHP2 activation leads to increased SOCS3 @-@ mRNA levels , whereas increased expression of SOCS3 results in a reduction of SHP2 phosphorylation after activation of the interleukin @-@ 6 signal transduction pathway .
0-1.1.1 1-1.1.1.1.r 2-1.1.1.1.1.1.1 3-1.1.1.1 4-1.1 5-1.1.2.r 6-1.1.2.1 7-1.1.2.2.2.1.1 9-1.1.2.2.1.1 10-1.1.2 12-1 13-1.1.2.1 13-1.2.1.2 14-1.2.1 15-1.2.1.1.r 16-1.2.1.1 17-1.2 18-1.2.2.r 20-1.2.2 21-1.2.2.2.r 22-1.2.2.2.1 23-1.2.2.2 24-1.2.3 25-1.2.3.1 26-1.2.3.1.1.r 28-1.2.3.1.1.1.1.1.1.1 30-1.2.3.1.1.1.1.1.1.1 31-1.2.3.1.1.1.1 32-1.2.3.1.1.1 33-1.2.3.1.1
10777583
bel_pmid_1077_7583.7596
JAK1
PKI166
RNA
17
0-1.1.1 1-1.1 3-1 4-1.4.r 5-1.4.1.2.1 6-1.4 7-1.2.r 8-1.2.1.1 10-1.2.1.1 13-1.2.2 14-1.2.2.1 15-1.2.2.1.1.r 16-1.2.2.1.1.1.1 19-1.2.2.2.4 25-1.2.2.2.1.1 26-1.2.2.2.1 27-1.2.2.2.1 31-1.2.2.2.3.1 32-1.2.2.2.3 33-1.2.2.2.3.2 35-1.3.1.1 40-1.3.1 41-1.3.1.2 42-1.3.1.2.1.1 42-1.3.1.2.1.1.r 43-1.3.1.2.1
a_pmid_2488_5690.39
This genotype was verified by DNA sequencing in RKO @-@ E1 , a subclone obtained from RKO that was found to be comparable to the parental cell line in terms of morphology and proliferation ( Figure <xref ref-type="fig" rid="F1"> 1 </xref>@ B and data not shown ) .
SDL-AMR-09
24885690
IGF-I
Cancer
cancer
V600E
B-Raf
We hypothesized that MEK inhibition activates AKT by inhibiting ERK activity , which blocks an inhibitory threonine phosphorylation on the JM domains of EGFR and HER2 , thereby increasing ERBB3 phosphorylation .
bio.bmtr_0002.8
SDL-AMR-09
0-1.1 1-1 2-1.2.r 3-1.2.1.1.1.1 4-1.2.1 4-1.2.3 5-1.2 6-1.2.2.1.1 8-1.2.3 9-1.2.3.2.1.1.1 10-1.2.3.2 13-1.2.3.3 15-1.2.3.3.1.2 16-1.2.3.3.1.1.1.1 17-1.2.3.3.1 20-1.2.3.3.1.1.2.1.1 21-1.2.3.3.1.1.2.1.2 23-1.2.3.3.1.1.2.2.1.1.1 25-1.2.3.3.1.1.2.2.2.1.1 27-1.2.3.r 28-1.2.3.3.2 29-1.2.3.3.2.1.1.1.1 30-1.2.3.3.2.1
1
-
1-1 3-1.1.2.1.1 5-1.1.2.1.1 6-1.1.3 11-1.1.1.1.1.1 12-1.1.1 14-1.1.3 15-1.1.3 15-1.1.3.1.r 16-1.1.3.1.1 17-1.1.3.1
SDL-AMR-09
In contrast , hKSR @-@ 2 up @-@ regulated the Rafmediated MEK activation by up to 70 % .
bio.bel_0002.12
SDL-AMR-09
ASPP2 phosphorylation was rapid and transient as 3 hours after EGF stimulation phosphorylated ASPP2 was barely detectable .
0-1.2.1.1.1.1 1-1.2.1 2-1.1.1.r 3-1.1 4-1 5-1.2 6-1.3.1.2.r 7-1.3.1.2.2.1 8-1.3.1.2.2.2 9-1.3.1.2 10-1.3.1.2.1.1.1.1 11-1.3.1.2.1 12-1.3.1.1.1.2 13-1.3.1.1.1.1.1 15-1.3.1.1.2 16-1.3.1.1
bmtr_0007.9
Erk
e
2
70
beta-catenin
S365A
DMSO
bel_pmid_1064_0734.39826
0-1 2-1.1.1.1.1.1 3-1.1.1 3-1.1.2.2.2 4-1.1 5-1.1.2.2 5-1.1.2.2.1 5-1.1.2.2.1.r 6-1.1.2.1.1.1 7-1.1.2 8-1.1.2.2.2.r 10-1.1.2.2.2.1.r 11-1.1.2.2.2.1.1.1 13-1.1.1.1.1.1 16-1.1.3 18-1.1.1.1.1.1 19-1.1.1 21-1.1 21-1.1.3.1.1.2 22-1.1.2 22-1.1.3.1.1 24-1.1.2.1.1.1 29-1.1.3.1.2.r 30-1.1.3.1.2 33-1.1.2.2.2.2.r 34-1.1.2.2.2.2
SDL-AMR-09
However , BCR ligation induced stronger ERK phosphorylation than coligation of CD72 with BCR did , indicating that BCR ligation @-@ induced phosphorylation of ERK is down @-@ modulated when CD72 is coligated with BCR .
10640734
B-Raf
c
753
threonine
GTP
p6
-
Following expression of BRAFV600E in melanocytes , the majority of cells became senescent ( Figure 1D and data not shown ) , consistent with previous studies ( Michaloglou et al. , 2005 )
bio.bel_0002.7
0-1.3 1-1.3.1 4-1.3.1.2.r 5-1.3.1.2 8-1.1.1 9-1.1.1.r 10-1.1 11-1 12-1.2 14-1.4.1.1 15-1.4.1.1.1 16-1.4.1 17-1.4.1.2 18-1.4.1.2.1.1 18-1.4.1.2.1.1.r 19-1.4.1.2.1 22-1.5 23-1.5.1.r 24-1.5.1.1 25-1.5.1 27-1.5.1.2.1.1.1.1.1 28-1.5.1.2.1.1 29-1.5.1.2.1.1.2.1 31-1.5.1.2.1.2.1
SDL-AMR-09
-
PMC3537887
bio.mskcc_0001.15
All four of these identified sites are followed by a proline residue , and their phosphorylation could be blocked by pretreating cells with the MEK inhibitor U0126 ( Fig . 2A ) , suggesting that these residues are feedback targets of the proline @-@ directed kinase , ERK .
SDL-AMR-09
0-1.1.2.2 1-1.1.2.1 3-1.1.2.3 4-1.1.2.4 5-1.1.2 7-1.1 8-1.1.1.r 10-1.1.1.1.1.1 11-1.1.1 13-1 14-1.2.1.2.1 14-1.2.1.2.1.r 15-1.2.1.2 16-1.2 18-1.2.1 21-1.2.1.1.1 24-1.2.1.1.2.2.1.1.1 25-1.2.1.1.2 25-1.2.1.1.2.2 25-1.2.1.1.2.2.r 26-1.2.1.1.2.1.1 28-1.2.2.1 30-1.2.2.1.1 33-1.3 35-1.1.2.3 36-1.1.1 38-1.3.1 39-1.3.1.1.r 42-1.3.1.1 44-1.3.1.2.2 45-1.3.1.2 47-1.3.1.2.1.1
1
Raf
IL-6
SDL-AMR-09
bio-kappa_0001.21
0-1.1 1-1 2-1.2 3-1.2.1.r 4-1.2.1.2.1 6-1.2.1 6-1.2.1.2 6-1.2.1.2.r 7-1.2.1.1.1 10-1.2.2.1 11-1.2.2 15-1.2.3 16-1.2.3.1.r 17-1.2.3.1.1.1 18-1.2.3.1.1.2 21-1.2.3.1.1.3 22-1.2.3.1.1.4
Activation requires dissociation of protein - bound GDP , an intrinsically slow process that is accelerated by guanine nucleotide ' 96 exchange factors ( GEFs ) .
CD72
-
GAP
B-Raf
Ras
0-1.1.3 1-1.1.3.1 3-1.1.2 4-1.1 4-1.1.1 4-1.1.1.r 5-1 7-1.2 10-1.2.1.1.1 10-1.2.1.1.2 11-1.2.1.1.1.1.r 13-1.2.1.1.1.1.1.1.1 15-1.2.1.1.1.1.1.1.1 17-1.2.1.1.1.1.1.1.1 18-1.2.1.1.1.1 21-1.2.1.1.1.2.4.1.1 21-1.2.1.1.1.2.4.2.1.1 21-1.2.1.1.2.2.4.1.1 23-1.2.1.1.1.2.4.1.1 23-1.2.1.1.2.2.4.1.1 25-1.2.1.1.1.2.4 25-1.2.1.1.2.2.4 27-1.2.1.1.1.2.4.1.1 27-1.2.1.1.1.2.4.2.1.1 27-1.2.1.1.2.2.4.1.1 29-1.2.1.1.1.2.4.2.1.1 29-1.2.1.1.2.2.4.2.1.1 30-1.2.1.1 32-1.2.1.1.1.2.4.1.1 32-1.2.1.1.1.2.4.2.1.1 32-1.2.1.1.2.2.4.1.1 34-1.2.1.1.1.2.4.1.1 34-1.2.1.1.2.2.4.1.1 36-1.2.1.1.1.2.4 36-1.2.1.1.2.2.4 37-1.2.1.1.2.2.r 38-1.2.1.1.2.2.4.2.1.1 40-1.2.1.1.1.2.4.2.1.1 40-1.2.1.1.2.2.4.2.1.1 41-1.2.1 43-1.2.1.2.2 44-1.2.1.2 48-1.2.1.2.1 51-1.2.1.1.1.1.1 51-1.2.1.1.1.2.4 51-1.2.1.1.2.2.4 53-1 54-1.2.1.2.1.1.3 55-1.2.1.2.1.1 57-1.3.1 59-1.3.1.1
SDL-AMR-09
bio.mskcc_0001.57
Taken together , these findings suggest a model whereby the binding of a 14 @-@ 3 @-@ 3 dimer to the C @-@ terminal pS621 site of C @-@ Raf and the C @-@ terminal pS729 site of B @-@ Raf provides the stable docking event that then allows the two proteins to make additional contacts ( Fig . 9 ) .
72
1B
SDL-AMR-09
As RAS is upstream of several signalling cascades [ 13 ] , we queried whether the activity of ASPP2 is regulated by the activation of a RAS @-@ mediated signalling pathway .
bio.bmtr_0005.5
1-1.3.1.1.1.1 2-1.3.1 3-1.3.1.2.2 5-1.3.1.2.1.2 6-1.3.1.2.1.1 7-1.3.1.2.1 9-1.3.1.3.1.1.1 12-1.1 13-1 16-1.2.2 17-1.2.2.1.r 18-1.2.2.1.1.1 20-1.2 21-1.2.1.r 23-1.2.1 24-1.2.1.1.r 26-1.2.1.1.1.1.1 28-1.2.1.1.1.1 29-1.2.1.1.1 30-1.2.1.1
bio.chicago_2015.18587
The copurification suggested that BMP @-@ 1 and BMP @-@ 2 might physically interact , leading to the idea that Tolloid might increase DPP activity by proteolytically processing DPP precursors ( Shimell et al. , 1991 ; Childs and O'Connor , 1994 ; Finelli et al. , 1994 ) .
2-1 3-1.2.r 4-1.2.1.1.1.1 4-1.2.1.2.1.1 6-1.2.1.1.1.1 8-1.2.1.1.1.1 8-1.2.1.2.1.1 10-1.2.1.2.1.1 11-1.2 12-1.2.1.3 12-1.2.1.3.r 13-1.2.1 15-1.3 16-1.3.1.r 18-1.3.1 20-1.3.1.1.1.1.1.1 21-1.3.1.1 22-1.3.1.1.1 23-1.3.1.1.1.2.1.1.1 24-1.3.1.1.1.2 27-1.3.1.1.1.3 28-1.3.1.1.1.3.1.1 29-1.3.1.1.1.3.1 31-1.4.1.1.1.1.1.1 32-1.4.1.1.1 33-1.4.1.1.1.2.1 35-1.4.1.1.2.1 37-1.4.1.2.1.1.1.1 38-1.4.1.2.1 39-1.4.1.2.1.2.1.1 41-1.4.1.2.2.1 43-1.4.1.3.1.1.1.1 44-1.4.1 44-1.4.1.2.1 44-1.4.1.3.1 45-1.4.1.3.1.2.1 47-1.4.1.3.2
SDL-AMR-09
SDL-AMR-09
antibody , a non @-@ radioactive in vitro phosphorylation assay was performed on the purified GST @-@ ASPP2 fragment ( 693 @-@ 1128 ) with recombinant MAPK1 .
3-1.1.1.2.1 3-1.1.1.2.1.r 5-1.1.1.2 6-1.1.1.1 7-1.1.1.1 8-1.1.1 9-1.1 11-1 12-1.2.r 14-1.2.3 15-1.2.1.1.1 17-1.2.1.1.1 20-1.2.2.1 22-1.2.2.2 24-1.1.2.r 25-1.1.2 25-1.1.2.2 25-1.1.2.2.r 26-1.1.2.1.1
bmtr_0007.5
8
GNBP
PKI166
bmtr_0006.9
Although current methods do not allow for detection of nucleotide @-@ free GTPases in vivo , our BiFC results provide additional support for our model .
0-1.4.r 1-1.4.2.1 2-1.4.2 4-1.4.1 4-1.4.1.r 5-1.4 6-1.4.3.r 7-1.4.3 8-1.4.3.1.r 9-1.4.3.1.2.1 11-1.4.3.1 11-1.4.3.1.2 11-1.4.3.1.2.r 13-1.4.3.2 14-1.4.3.2 16-1.1.2 16-1.1.2.r 18-1.1 18-1.1.1 18-1.1.1.r 19-1 21-1.2 22-1.3.r 23-1.3.1 23-1.3.1.r 24-1.3
SDL-AMR-09
1998
ubiquitin
2-1 3-1.2 4-1.1.r 5-1.1.1.1 6-1.1.1 8-1.1.1.2 9-1.1.1.2.1.r 10-1.1.1.2.1.1.1 13-1.1.1.2.2.r 15-1.1.1.2.2 17-1.1.1.2.3.1.1.1 19-1.1.1.2.3 24-1.1.1.1 24-1.1.1.1.1 24-1.1.1.1.1.r 25-1.1.2 26-1.1.2.2 27-1.1.2.2.1.r 29-1.1.2.2.1.1.1 30-1.1.2.2.1.1 30-1.1.2.2.1.2 31-1.1.2.2.1.1.2.1.1 32-1.1.2.2.1 33-1.1.2.2.1.2.1.1.1 35-1.1.2.2.1.2.1.1.1 37-1.1.2.2.1 38-1.1.r 39-1.1.3.1 40-1.1.3.1.1.r 42-1.1.3.1.1.1 43-1.1.3.1.1 44-1.1.3.1.1.2.r 45-1.1.3.1.1.2 46-1.1.3 47-1.1.3.2.2.1 47-1.1.3.2.2.1.2 47-1.1.3.2.2.1.2.1.2.1 47-1.1.3.2.2.1.2.r 48-1.1.3.2.2.1.1.1 50-1.1.3.2.2 51-1.1.3.2 51-1.1.3.2.1 51-1.1.3.2.1.r
SDL-AMR-09
bio.bmtr_0004.17
It was established recently that monoubiquitination increases the proportion of Ras that is in the activated ( GTP @-@ bound ) state , that monoubiquitination enhances association with the downstream effectors Raf and PI3 @-@ Kinase , and that mutation of the primary site of monoubiquitination impairs oncogenic Ras @-@ mediated tumorigenesis .
C
-
RasGEF
bio.mskcc_0001.23
0-1.1.1 1-1.1 3-1 8-1.2.2.1.1 8-1.2.2.1.1.2 8-1.2.2.1.1.2.r 9-1.2 10-1.2.1.1.1 10-1.2.1.1.1.2 10-1.2.1.1.1.2.1.2.1 10-1.2.1.1.1.2.r 11-1.2.1.1.1.1.1 13-1.2.1.1.1.1.1 13-1.2.1.1.2.1.1 14-1.2.1.2.1.3 14-1.2.1.2.1.4.1 15-1.2.1.1.1 15-1.2.1.1.1.2 15-1.2.1.1.1.2.r 16-1.2.1.1 16-1.2.2.1 18-1.2.1.1.2.1.1 18-1.2.1.2.1.3.1.1 20-1.2.1.1.1.1.1 20-1.2.1.1.2.1.1 23-1.2.1.1.2.1.1 23-1.2.1.2.1.3.1.1 25-1.2.1.2.1.3.1.1 26-1.2.1.2.1.4.1.1.1 28-1.2.1.2.1.4.1.1.1 30-1.2.1.2.1.4.1.1.1 31-1.2.1.2.1.4 32-1.2.1.2.1.3 33-1.2.1.1.2.r 34-1.2.1.1.2.1.1 36-1.2.1.1.1.1.1 36-1.2.1.1.2.1.1 36-1.2.2.1.1.1.1 41-1.2.1.2.1.r 42-1.2.1.2 44-1.1.2.1.1 46-1.1.2.1.2 49-1.2.3.1 51-1.2.3.1.1
Previous studies have shown that , for both normal and oncogenic B @-@ Raf proteins to heterodimerize with C @-@ Raf , the C @-@ terminal 14 @-@ 3 @-@ 3 binding site of C @-@ Raf ( S621 ) must be intact ( 11 , 27 ) ( Fig . 3E ) .
SDL-AMR-09
alpha-catenin
AP-2
RBW-1
SDL-AMR-09
During gastrulation , DLT may first form a complex with CRB to target it to the apical domain .
bio.chicago_2015.18761
0-1.2.r 3-1.1.1.1.1.1 4-1 5-1.1.4 6-1.1 8-1.1.2 9-1.1.1.r 10-1.1.1.2.1.1 12-1.1.3 14-1.1.3.2.r 16-1.1.3.2.1 17-1.1.3.2
-
Axin
bio.bmtr_0002.11
1-1 4-1.1.1.1.1 4-1.1.2.1.1.2.1.1 5-1.1.1.2.1 6-1.1.1 6-1.1.1.2 6-1.1.1.2.r 7-1.1 9-1.1.2.1.2 10-1.1.2.1.1.2.1.1 11-1.1.2 12-1.1.2.2.2.1.1 13-1.1.2.1.1.1.1 13-1.1.2.2.1.1.1 14-1.1.2.1 14-1.1.2.2 17-1.1.2.3.1 17-1.1.2.3.1.r 18-1.1.2.3 19-1.1.2.3.2.r 20-1.1.2.3.2.1.1.1 21-1.1.2.3.2
SDL-AMR-09
In contrast , the EGFR T669A mutant increased both basal EGFR and ERBB3 tyrosine phosphorylation that was not augmented by MEK inhibition .
AZD6244
p3
HER2
-
U0126
U0126
C-Raf
8
SDL-AMR-09
This showed that PKI166 alone or in combination with U0126 induced apoptosis in the EGFR or HER2 expressing cell lines MDA @-@ MB @-@ 231 , MDA @-@ MB @-@ 468 , SKBR3 and SUM149 cells ( <xref ref-type="fig" rid="fig3"> Figure 3 </xref> ) , although the proportions of hypodiploid cells varied between the different lines .
0-1.1 1-1 2-1.2.r 3-1.2.1.1.1.1 3-1.2.1.2.1.1 4-1.2.1.1.2 5-1.2.1 7-1.2.1.2 7-1.2.1.2.2 7-1.2.1.2.2.r 8-1.2.1.2.2.1.r 9-1.2.1.2.2.1.1.1 10-1.2 11-1.2.2 12-1.2.5.r 14-1.2.5.5.1.1.1.1 15-1.2.5.5.1 16-1.2.5.5.1.2.1.1 17-1.2.5.5 18-1.2.5.1 19-1.2.5.1 20-1.2.5.1.1.1 22-1.2.5.1.1.1 24-1.2.5.1.1.1 26-1.2.5.1.1.1 26-1.2.5.2.1.1 28-1.2.5.1.1.1 28-1.2.5.2.1.1 30-1.2.5.2.1.1 32-1.2.5.3.1.1 33-1.2.5 34-1.2.5.4.1.1 35-1.2.5.1 35-1.2.5.2 35-1.2.5.3 35-1.2.5.4 38-1.2.3.1 39-1.2.3.1.1 43-1.2.4.r 45-1.2.4.1 46-1.2.4.1.1.r 47-1.2.4.1.1.1 48-1.2.4.1.1 49-1.2.4 52-1.2.4.2.1 53-1.2.4.2
15280923
pmid_1528_0923.100
26
Notch
Suppression of the PAF effects by calphostin C , a PKC inhibitor , suggests that PKC is an upstream activator of FAK
bel_pmid_1072_9607.22074
SDL-AMR-09
0-1.1 1-1.1.1.r 3-1.1.1.2.1.1 4-1.1.1 5-1.1.1.1.r 6-1.1.1.1 7-1.1.1.1.1.1 10-1.1.1.1.2.1.1.1.1.1 11-1.1.1.1.2.1 11-1.1.1.1.2.1.1 11-1.1.1.1.2.1.1.r 13-1 14-1.2.r 15-1.2.1 18-1.2.3 19-1.2 20-1.2.2.r 21-1.2.2.1.1
10729607
In the case of C @-@ Raf , six sites of feedback phosphorylation have been identified , five of which are direct targets of activated ERK ( 8 )
4-1.1.2.1.1 6-1.1.2.1.1 8-1.1.1 9-1.1 9-1.1.4.1 10-1.1.3.r 11-1.1.3.1 12-1.1.3 15-1 17-1.1.4.1.1 21-1.1.4.1.2.2 22-1.1.4.1.2 23-1.1.4.1.2.1.r 24-1.1.4.1.2.1.2 25-1.1.4.1.2.1.1.1 27-1.2.1.1.1
SDL-AMR-09
bio.mskcc_0001.48
Towards the center of the gradient , high levels of Dpp signaling strongly repress brk transcription .
SDL-AMR-09
bio.chicago_2015.19256
0-1.3.r 2-1.3 3-1.3.1.r 5-1.3.1 7-1.1.1 8-1.1 9-1.1.2.r 10-1.1.2.1.1.1 11-1.1.2 12-1.4 13-1 14-1.2.1.1.1 15-1.2
15280923
SDL-AMR-09
Immunoblotting revealed differences in basal levels of ERK1 @/@ 2 phosphorylation in different breast cancer cell lines , while the expression of ERK1 @/@ 2 protein , normalised to actin expression , was relatively consistent ( <xref ref-type="fig" rid="fig1"> Figure 1A </xref> ) .
pmid_1528_0923.68
0-1.1.1 1-1.1 2-1.1.2 3-1.1.2.1.r 4-1.1.2.1.1 5-1.1.2.1 6-1.1.2.1.2.r 7-1.1.2.1.2.1.1.1 9-1.1.2.1.2.1.1.1 10-1.1.2.1.2 11-1.1.2.1.2.2.r 12-1.1.2.1.2.2.2 13-1.1.2.1.2.2.1.2.1 14-1.1.2.1.2.2.1.2.2 15-1.1.2.1.2.2 16-1.1.2.1.2.2 18-1 20-1.2.1.3 22-1.1.2.1.2.1.1.1 24-1.1.2.1.2.1.1.1 25-1.2.1.3.1 29-1.2.1.3.1.1.1 30-1.2.1 30-1.2.1.3 30-1.2.1.3.r 33-1.2.2 34-1.2 37-1.3.1 38-1.3.1.1
ERK
This model explains why C @-@ Raf mutants devoid of kinase activity cannot function as activators , and why B @-@ Raf can activate Mek directly as a homodimer .
0-1.1.1 1-1.1 2-1 3-1.2 3-1.2.1 3-1.2.1.r 4-1.2.1.1.1.2.1.1.1 6-1.2.1.1.1.2.1.1.1 7-1.2.1.1.1.2.1 7-1.2.1.1.1.2.1.2 7-1.2.1.1.1.2.1.2.r 10-1.2.1.1.1.2.1.3.1.1 11-1.2.1.1.1.2.1.3.1 12-1.2.1.1.1 12-1.2.1.1.1.1 12-1.2.1.1.1.1.r 15-1.2.1.1.1.2 17-1.2.1.1 18-1.2 18-1.2.1 18-1.2.1.r 19-1.2.1.1.2.1.1.1.1 21-1.2.1.1.2.1.1.1.1 22-1.2.1.1.2 23-1.2.1.1.2.1 24-1.2.1.1.2.1.2.1.1 25-1.2.1.1.2.1.3 28-1.2.1.1.2.1.1.2.1
SDL-AMR-09
bio-kappa_0001.7
-
C-Raf
5.0
1
2
1
lysine
170
Ectopic Gem or Rad expression inhibits ROK @-@ dependent functions such as formation of stress fibers and focal adhesions , neurite retraction , and Rho @-@ dependent transformation .
0-1.1.1.3 1-1.1.1.1.1.1 3-1.1.1.2.1.1 4-1.1 5-1 6-1.2.1.1.1.1 8-1.2.1 9-1.2 10-1.2.2.r 11-1.2.2.r 12-1.2.2.1 13-1.2.2.1.1.r 14-1.2.2.1.1.1.1 15-1.2.2.1.1.1 16-1.2.2.1.1 17-1.2.2.1.1.2.1 18-1.2.2.1.1.2 20-1.2.2.2.1.1.1 21-1.2.2.2 23-1.2.2 24-1.2.2.3.1.1.1.1 26-1.2.2.3.1 27-1.2.2.3
bio.chicago_2015.19362
SDL-AMR-09
46
EGFR
-
8505C
interrogative
G1
C-Raf
bio.bmtr_0004.15
0-1.1.1 1-1.1 2-1 3-1.2.1 3-1.2.1.r 4-1.2.3 5-1.2.3 6-1.2 7-1.2.2.r 8-1.2.2.1 8-1.2.2.1.1 8-1.2.2.1.1.r 9-1.2.2 11-1.2.2.2 12-1.2.2.2.1.r 13-1.2.2.2.1 13-1.2.2.2.1.2 13-1.2.2.2.1.2.r 15-1.2.2.2.1.3.1.1.1 17-1.2.2.2.1.3 18-1.2.2.2.1.1.1 21-1.2.2.3 22-1.2.2.3.1.r 22-1.2.3 23-1.2.2.3.1 24-1.2.2.3.1.1.r 25-1.2.2.3.1.1.1.1.1.1 27-1.2.2.3.1.1.1 28-1.2.2.3.1.1
These data support our in vitro findings that monoubiquitination increases the population of active , GTP @-@ bound Ras through a defect in sensitivity to GAP @-@ mediated regulation .
SDL-AMR-09
Smith
0-1.4 1-1.4.1.r 3-1.4.1 5-1.4.1.1.1 6-1.4.1.1 7-1.4.1.1.2.1.1.1 9-1.4.1.1.2.1.1.1 10-1.4.1.1.2 11-1.4.1.1.3.r 12-1.4.1.1.3 14-1.4.1.1.3.2 15-1.4.1.1.3.2.1.r 17-1.4.1.1.3.2.1.2 18-1.4.1.1.3.2.1 20-1.2 21-1.2.1.r 23-1.2.1.1.1 24-1.3.1.1.3.2 25-1.3.1.1.3 26-1.1 26-1.1.r 26-1.3.1.1.3.1 26-1.3.1.1.3.1.r 27-1 30-1.3.1 33-1.3.1.1.2.1 36-1.3.1.1.1.1 36-1.4.1.1.2.1.1.1 38-1.3.1.1.1.1 38-1.4.1.1.2.1.1.1 43-1.4.1.1.3.2.1 44-1.3.1.1.3.2.1.r 45-1.3.1.1.3.2.1.1 46-1.3.1.1.3.2.1
SDL-AMR-09
bio.mskcc_0001.46
Consistent with the model that Pin1 influences B @-@ Raf signaling by facilitating the dephosphorylation of the feedback sites , overexpression of the Pin1 proteins had no effect on the transformation potential of G466A FBm @-@ B @-@ Raf , which lacks the sites of feedback phosphorylation .
e
15280923
pmid_1528_0923.78
Similarly , no correlation was found between the expression of HER2 receptor and the status of pERK ( <xref ref-type="fig" rid="fig1"> Figure 1A </xref> ) .
SDL-AMR-09
0-1.2 2-1.1.1 2-1.1.1.r 3-1.1 5-1 8-1.1.2 9-1.1.2.1.r 10-1.1.2.1.1.1.1 11-1.1.2.1 14-1.1.3 15-1.1.3.1.r 16-1.1.3.1.1.1 16-1.1.3.1.2 19-1.3.1 20-1.3.1.1
S729A
alphaFtz-F1
1-1.3 2-1.3.1.1 2-1.3.1.1.r 4-1.3.1.2.1.2 5-1.3.1.2.1.1.1 7-1.3.1.2.1.1.1 8-1.3.1.2 10-1.3.1 12-1.3.1.3.1 13-1.3.1.3 14-1.3.1.3.1.1.r 15-1.3.1.3.1.1 16-1.3.1.3.1.1.1.r 17-1.3.1.3.1.1.1 19-1.1 21-1 22-1.2.r 24-1.2 25-1.2.1.r 26-1.2.1.1.1 28-1.2.2.1.1 31-1.2.2 31-1.2.2.2 31-1.2.2.2.r 32-1.2.2.2.1.r 33-1.2.2.2.1.1.1 36-1.4.1 37-1.4.1.1
SDL-AMR-09
To test whether the basal ERK1 @/@ 2 activity was providing an escape mechanism from inhibition by PKI166 , cells were treated with a combination of PKI166 and UO126 , an inhibitor of MEK ( <xref ref-type="table" rid="tbl1"> Table 1 </xref> ) .
pmid_1528_0923.93
15280923
GSK-3beta
-
SDL-AMR-09
P @-@ TEFb may alter the role of Spt proteins either by phosphorylation of Pol II or Spt5 ( Ivanov et al. 2000 ) .
bio.chicago_2015.19095
0-1.1.1.1.1 0-1.1.3 2-1.1.1.1.1 3-1 4-1.1 6-1.1.2 8-1.1.2.1.1.1 9-1.1.1 9-1.1.2.1 9-1.1.3.1.2 12-1.1.3 13-1.1.3.1.r 14-1.1.3.1.1.1.1 15-1.1.3.1.1.1.2 16-1.1.3.1 17-1.1.3.1.2.1.1 19-1.2.1.1.1.1.1 20-1.2.1.1 21-1.2.1.1.2.1 22-1.2.1.2.1
-
e
DNA
ATF-1
EGFR
STAT5
247
SDL-AMR-09
1-1.3 3-1.3.1.1 4-1.3.1 5-1.3.1.2.r 6-1.3.1.2 7-1.3.1.2 9-1.1 10-1 13-1.2.1.1.2.1.1.1.1 14-1.2.1.1.2.1 15-1.2.1.1.2 16-1.2.1.1.2.2.1.1.1 18-1.2.1.1.2.2.1.1.1 19-1.2.1.1.2.2.1.2.1 20-1.2.1.1.2.2 21-1.2.2 26-1.2.2.1.1.1 28-1.2.2.1.1.1.1.1.1 29-1.2.2.1.1.1.1.1.2 30-1.2.2.1.1 31-1.2.2.1.1.2.1.1.1 32-1.2.2.1.1.2.1.1.2 33-1.2.2.1.1 34-1.2.2.1.1 36-1.2.2.1.1.3.1.1.1 37-1.2.2.1.1.3.1.1.2 39-1.2.2.1.1 42-1.2.2.2.r 43-1.2.2.2.1.1.1.1 44-1.2.2.2.1 46-1.2.2.2 48-1.2.2.1.1.4 50-1.2.2.1.1.1.1.1.1 51-1.2.2.1.1.1.1.1.2 53-1.2.2.1.1.2.1.1.1 54-1.2.2.1.1.2.1.1.2 56-1.2.2.1.1 57-1.2.2.1.1.3.1.1.1 58-1.2.2.1.1.3.1.1.2 59-1.2.2.1.1.1 59-1.2.2.1.1.2 59-1.2.2.1.1.3 61-1.2.1 61-1.2.2 63-1.2.2.1 64-1.2.2.1.2.1.1.1 65-1.2.2.1.2 66-1.2.2.1.3.r 68-1.2.2.1.3.1 69-1.2.2.1.3
By using a refined model of megakaryocytic differentiation , we found that either TPO stimulation or Ha @-@ Ras G12V expression could up @-@ regulate the expression of cyclin D1 and cyclin D2 in addition to cyclin D3 , and that , when cdc2 activity was suppressed , each of cyclin D1 , cyclin D2 , and cyclin D3 expression was able to induce megakaryocytic differentiation with a similar efficiency .
10681535
bel_pmid_1068_1535.24496
50
Sca
DBA2 mouse
-
SH3 domain
SDL-AMR-09
As a consequence the GDP produced by GTP hydrolysis on Ras is trapped and the bulk of cellular Ras accumulates in the GDP - bound ‘ off ’ state , despite the high GTP / GDP ratio in the cytosol ( 1 – 3 ) .
bio.ras_0001.6
0-1 1-1 2-1 4-1.1.1.1.1.1 7-1.1.1.1.2.1.1.1 8-1.1.1.1.2 10-1.1.1.1.2.1.2.1.1.1 12-1.1.1 13-1.1 15-1.1.2.1.2.2 17-1.1.2.1.2.1.2 18-1.1.2.1.1.1 18-1.1.2.1.2.1.1.1 19-1.1.2 22-1.1.1.1.1.1 24-1.1.1.1.2.1 24-1.1.1.1.2.1.2 24-1.1.1.1.2.1.2.r 24-1.1.2.1 24-1.1.2.1.4 24-1.1.2.1.4.r 30-1.1.2.2.r 32-1.1.2.2 33-1.1.2.2.1.2 34-1.1.2.2.1.2 35-1.1.2.2.1.2 36-1.1.2.2.1 37-1.1.2.2.1.3.r 39-1.1.2.2.1.3 41-1.2.1.1.1.1 43-1.2.1.1.1.2
SDL-AMR-09
0-1.4.r 1-1.4.1.2 2-1.4.1.1.1 2-1.4.2.1.1 4-1.4 6-1.4.1.1.1 6-1.4.2.1.1 11-1.4.2.2 13-1.4.2.2 17-1.1.1.1.1 18-1.1 19-1 20-1.2.r 21-1.2.3 22-1.2.2 23-1.2 24-1.2.1.r 25-1.2.1.1.1 26-1.2.1.2 28-1.3.1 29-1.3.1.1
bio.bmtr_0002.17
When endogenous EGFR was replaced with EGFR ( exon19 del ) wild @-@ type at T669 , MEK inhibition led to significant feedback activation of ERBB3/PI3K/AKT signaling ( Figure 6C ) .
K-Ras
APC
SDL-AMR-09
0-1.1.1.1 1-1.2.1.1 2-1.3 3-1.3.1 5-1.3.2 5-1.3.2.r 6-1.3.2.1 8-1.3.2.2 9-1.3.2.2.1.r 10-1.3.2.2.1.1.1.1 10-1.3.2.2.1.1.1.1.r 12-1.3.2.2.1.1.1.2 13-1.3.2.2.1.1.1 14-1.3.2.2.1.1 14-1.3.2.2.2.1.1 15-1.3.2.2.1 16-1.3.2.2.1.2.r 17-1.3.2.2.1.2.1.1 18-1.3.2.2.1.2.1 20-1.3.2.2.1.2 22-1.3.2.2.2 23-1.3.2.2.2.1.r 24-1.3.2.2.2.1.4 26-1.3.2.2.2.1 27-1.3.2.2.2.1.1.1.r 28-1.3.2.2.2.1.1.1 30-1.3.2.2.1.1.1 31-1.3.2.2.1.1 34-1.3.2.2.1.2.1.1 35-1.3.2.2.1.2.1 36-1.3.2.2.1.2
bio.bel_0002.13
GSK PI3K Phase 2 , part 1 : List of non @-@ position specific phosphorylation effects on parent protein 's activity , derived from existing causal assertions of position @-@ specific phosphorylations on the parent protein activity .
29
Ras
GAP
-
GTP
SUM149
p
MAPK
SDL-AMR-09
0-1.3 1-1.3 2-1 3-1.1.r 4-1.1.1.1 7-1.2.2.1.1 8-1.2.r 9-1.2.1.1.1 10-1.2 11-1.2.2.1.1 13-1.2.2.1.1
bio.chicago_2015.17550
In vivo binding of GSK @-@ 3 beta with Axin or beta @-@ catenin .
interrogative
B-Raf
SDL-AMR-09
bio.bmtr_0003.2
0-1.1 1-1.3 2-1 4-1.2 5-1.2.1 6-1.2.1.1.r 8-1.2.1.1 9-1.2.1.1.2.r 10-1.2.1.1.2.1.1 11-1.2.1.1.1.r 12-1.2.1.1.1.1.1.1.1 13-1.2.1.1.1.1.1 14-1.2.1.1.1 14-1.2.1.1.1.1 14-1.2.1.1.1.1.r 15-1.2.1.1.3.r 16-1.2.1.1.3.2.1.3.1.1 17-1.2.1.1.3.2.1.3 17-1.2.1.1.3.2.1.3.2 17-1.2.1.1.3.2.1.3.2.r 18-1.2.1.1.3.1 19-1.2.1.1.3 20-1.2.1.1.3
We next examined the mechanisms accounting for the increase in HER3 by MAPK pathway inhibitors in BRAF mutant thyroid cell lines .
dSir2
B-Raf
ERK
K-Ras
24
23
Ras
bio.bmtr_0005.2
0-1 1-1.1 3-1.1 5-1.2 5-1.2.1 5-1.2.1.r
Passage 1 @-@ 1 ( Results )
SDL-AMR-09
ceramide
Ras
-
-
1B
3C
27
0-1 0-1.1 0-1.1.r 1-1 1-1.1 1-1.1.r 4-1.1.4.2.1.1.1 6-1.1.4.2.1.1.1 7-1.1.4.2.2 8-1.1.4.2 10-1.1.4 13-1.1.4.1.r 14-1.1.4.1.1.1.1.1 15-1.1.4.1.1 16-1.1.4.1 18-1.1.4.1.2 19-1.1.4.1.2.1.r 20-1.1.4.1.2.1.3 22-1.1.4.1.2.1.2 23-1.1.4.1.2.1 26-1.1.1.1 27-1.1.1.1.1.r 29-1.1.1.1.1.1 30-1.1.1.1.1 31-1.1.1.1.1.2.r 32-1.1.1.1.1.2 33-1.1.1.1.1.2.2.r 34-1.1.1.1.1.2.2.1.1 36-1.1.1.1.1.2.2.1.1 38-1.1.1 40-1.1 41-1.1.2.1 42-1.1.2.1.1.r 43-1.1.2.1.1 44-1.1.2.1.1.1.r 45-1.1.2.1.1.1.1 46-1.1.2.1.1.1.1 47-1.1.2.1.1.1 49-1.1.2 50-1.1 50-1.1.5.1 51-1.1.3 53-1.1.5.1.1 53-1.1.5.1.2 55-1.1.5.1.1.1 56-1.1 56-1.1.5.1 57-1.1.1.1.1.2.2.1.1
In addition , when B @-@ Raf feedback phosphorylation was prevented , either by U0126 treatment or by mutation of all the feedback sites , an increase in the basal level of heterodimerization with C @-@ Raf was observed , and heterodimerization in response to growth factor treatment was increased and prolonged ( Fig . 3B and C ) .
bio.mskcc_0001.19
SDL-AMR-09
RAS
S1B
0-1.1.1.1 1-1.5 2-1 3-1.2.1.1 7-1.3.r 9-1.3.1.1 10-1.3.1.2 12-1.4.1.1.1.1.1.1 13-1.4.1.1.1 14-1.4.1.1.1.2.1.1 16-1.4.1.1.2.1 18-1.4.1.2.1.1.1.1 19-1.4.1.2.1 20-1.4.1.2.1.2.1.1 22-1.4.1.1.2.1 24-1.4.1.3.1.1.1.1 25-1.4.1.3.1 26-1.4.1.3.1.2.1.1 28-1.4.1.3.2
Dl then activates Notch ( N ) in the R4 precursor ( Cooper and Bray , 1999 ; Fanto and Mlodzik , 1999 ; Tomlinson and Struhl , 1999 ) .
SDL-AMR-09
bio.chicago_2015.17347
IL-8
GAP
22
26
SDL-AMR-09
24885690
1-1.1.1.3.1.1 2-1.1.1.3.1 5-1.1.1.2.1.1.1 7-1.1.1.2.1.1.1 8-1.1.1 8-1.1.1.2 8-1.1.1.2.r 9-1.1.1.1.1 11-1 13-1.1 15-1.1.2.3 16-1.1.2.2.1.1 18-1.1.2.2 19-1.1.2 20-1.1.2.1.r 21-1.1.2.1.1 22-1.1.2.1
Among tested agents , the B @-@ Raf inhibitor dabrafenib was found to induce a strong V600E @-@ dependent shift in cell viability .
a_pmid_2488_5690.11
serine
827
histidine
FGFR
MDA-MB-231
Hydrogen_peroxide
H2O2
BRAF
Cancer
cancer
Raf
N-terminus
2C
MDA-MB-231
22
It could be argued that GTP loading occurs prior to ubiquitination and that the GTP bound form of K @-@ Ras , via interaction with effectors , is preferentially mono @-@ ubiquitinated via a feedback mechanism .
SDL-AMR-09
bio.bmtr_0001.14
1-1 3-1.1 4-1.1.1.r 5-1.1.1.1.1.1.1 6-1.1.1.1 8-1.1.1.1.2 9-1.1.1.1.2.1.r 10-1.1.1.1.2.1 14-1.1.1.1.1.1.1 15-1.1.1.2.2 15-1.1.1.2.2.2 15-1.1.1.2.2.2.r 18-1.1.1.2.2.1.1 20-1.1.1.2.2.1.1 23-1.1.1.2.4 24-1.1.1.2.4.2.r 25-1.1.1.2.4.2 28-1.1.1.2.3 29-1.1.1.2.1 29-1.1.1.2.1.r 31-1.1.1.2 34-1.1.1.2.5
1-1.1.1.1 2-1 3-1.2 4-1.2.1.r 5-1.2.1.1.1.1 6-1.2.1 7-1.2.1.2.1.1 8-1.2.2.r 9-1.2.2.1.2.1 10-1.2.2.1.2.2 11-1.2.2
15280923
SDL-AMR-09
pmid_1528_0923.88
<sec-title level="2"> PKI166 inhibits phosphorylation of EGFR and HER2 in breast cancer cells </sec-title>
CTBP2
Ras
lysine
147
Gp150
p3
-
GEF
1-1 3-1.2.2 5-1.2.3 6-1.2.3.1.r 8-1.2.3.1.1 12-1.2.3.1.1.2 13-1.2.3.1 14-1.2.3.1.2 15-1.2.3.1.2.2.r 16-1.2.3.1.2.2.1.1 17-1.2.3.1.2.2
10851026
bel_pmid_1085_1026.6144
SDL-AMR-09
FGFs activate the endogenous FGFRs leading to the formation of a Grb2/FRS2/Shp2 complex and activation of MAP kinase .
SDL-AMR-09
0-1.3.3.r 1-1.1 2-1.3.3 3-1.3 5-1.3.2 6-1.3.2.1.r 7-1.3.2.1.1 8-1.3.2.1 13-1.3.2.2.1.1 13-1.3.2.2.1.1.2 13-1.3.2.2.1.1.2.1.2.1 13-1.3.2.2.1.1.2.r 14-1.3.2.2.1.1.1.1 16-1.3.2.2.1.1.1.1 16-1.3.2.2.1.2.1.1 17-1.3.2.2.1.1 17-1.3.2.2.1.1.2 17-1.3.2.2.1.1.2.r 21-1.3.2.2.1.2.1.1 23-1.3.2.2.1.1.1.1 23-1.3.2.2.1.2.1.1 25-1.1 26-1 27-1.2.r 29-1.2.1.1 29-1.2.1.2 29-1.2.1.3 31-1.2.1.1.1.3 31-1.2.1.2.1.3 31-1.2.1.3.1.3 32-1.2.1.1.1.1.1 32-1.2.1.2.1.1.1 32-1.2.1.3.1.1.1 34-1.2.1.1.1.1.1 34-1.2.1.1.1.2.1.1.1 34-1.2.1.2.1.1.1 34-1.2.1.2.1.2.1.1.1 34-1.2.1.3.1.1.1 34-1.2.1.3.1.2.1.1.1 35-1.2.1.1.1.2 35-1.2.1.2.1.2 35-1.2.1.3.1.2 37-1.2.1.1.1.2.1.1.1 37-1.2.1.2.1.2.1.1.1 37-1.2.1.3.1.2.1.1.1 37-1.2.2.1.1.1.1 39-1.2.1.1.1.1.1 39-1.2.1.1.1.2.1.1.1 39-1.2.1.2.1.1.1 39-1.2.1.2.1.2.1.1.1 39-1.2.1.3.1.1.1 39-1.2.1.3.1.2.1.1.1 39-1.2.2.1.1.1.1 40-1.2.2.1 41-1.2.1.1.1.2.1.r 41-1.2.1.1.1.r 42-1.2.1.1.1.2.1.3.2 44-1.2.1.1.1.2.1.2.1 47-1.2.1.2.1.2.1.3.2 49-1.2.1.2.1.2.1.2.1 52-1.2.1 53-1.2.1.3.1.2.1.3.1 55-1.2.1.3.1.2.1.2.1 57-1.2.1.1.1.2.1.3.1 57-1.2.1.2.1.2.1.3.1 58-1.2.1.3.1.2.1 58-1.2.1.3.1.2.1.3 58-1.2.1.3.1.2.1.3.r 60-1.2 61-1.3.3.r 63-1.2.2.1.2 64-1.2.2.1 66-1.2.1.1.1.2.1.2 66-1.2.1.2.1.2.1.2 66-1.2.1.3.1.2.1.2 66-1.2.2 68-1.2.3 69-1.2.3.1.r 70-1.2.3.1.1 71-1.2.3.1.1 72-1.2.3.1.3 73-1.2.3.1 75-1.2.3.1.2 75-1.3.2.2.1 77-1.3.2.2.1.1 77-1.3.2.2.1.1.2 77-1.3.2.2.1.1.2.1.2.1 77-1.3.2.2.1.1.2.r 78-1.2.1.3.1.2.1.1.1 78-1.2.2.1.1.1.1 78-1.3.2.2.1.1.1.1 80-1.2.1.3.1.1.1 80-1.2.1.3.1.2.1.1.1 80-1.2.2.1.1.1.1 80-1.3.2.2.1.1.1.1 80-1.3.2.2.1.2.1.1 81-1.2.2.1 83-1.2.4.1 85-1.2.1.3.1.r 85-1.2.4.1.1
When we next examined the effect of feedback phosphorylation on the ability of oncogenic B @-@ Raf to form heterodimers with C @-@ Raf , we found that the levels of endogenous C @-@ Raf associating with B @-@ Raf proteins of high ( V600E ) , intermediate ( G466A ) , and impaired ( D594G ) kinase activities all increased when the feedback sites were mutated , indicating that feedback phosphorylation also inhibits the heterodimerization of oncogenic B @-@ Raf proteins ( Fig . 3D ) .
bio.mskcc_0001.22
0.5
MEK
propidium iodide
B-Raf
-
CtBP
DLT Interacts with CRB and NRX IV
bio.chicago_2015.18617
0-1.1.1.1 1-1 2-1.2.r 3-1.2.1.1.1 4-1.2 5-1.2.2.1.1 6-1.2.2.1.2
SDL-AMR-09
bio.chicago_2015.18196
SDL-AMR-09
The major region of phosphorylation of beta @-@ catenin by CK2 is the central armadillo repeat domain , where carrier proteins like axin and the adenomatous polyposis coli gene product APC interact with beta @-@ catenin .
1-1.1 2-1 3-1.2.r 4-1.2 5-1.2.1.r 6-1.2.1.1.1 8-1.2.1.1.1 9-1.2.2.r 10-1.2.2.1.1 11-1.3.r 13-1.3.1.1 14-1.3.1.2 15-1.3.1.3 18-1.3.2.r 19-1.3.2.1.2 20-1.3.2.1 21-1.3.2.1.1.r 22-1.3.2.1.1.1.1.1 23-1.3.2.1.1 25-1.3.2.1.1.2.2.1.1.1 26-1.3.2.1.1.2.2.1.1.2 27-1.3.2.1.1.2.2.1.1.3 28-1.3.2.1.1.2.2.1 30-1.3.2.1.1.2.1.1 31-1.3.2 32-1.3.2.2.r 33-1.3.2.2 34-1.3.2.2 35-1.3.2.2
interrogative
--
SDL-AMR-09
bio.chicago_2015.18987
0-1.3.r 1-1.3.1.1 2-1.3.2 3-1.3 4-1.3.1 6-1.1 7-1 8-1.2.2 9-1.2 10-1.2.1.r 12-1.2.1.1.1.1 13-1.2.1 19-1.4 20-1.4.1.r 21-1.4.1.2 22-1.4.1.1.1 24-1.4.1.1 25-1.4.1 27-1.5.1.1.1
During cell morphogenesis and motility , cells undergo extensive remodeling of the actin cytoskeleton , a phenomenon that is mediated by various actin @-@ binding proteins ( 1 ) .
ATP
bio.ras_0002.2
0-1.1.2 1-1.1.1 2-1.1.3.1.1.1 3-1.1 3-1.1.3 3-1.1.3.r 4-1 5-1.2.r 6-1.2.1 6-1.2.1.r 7-1.2 8-1.2.2.r 10-1.2.2.3 11-1.2.2.3.r 12-1.2.2.4 13-1.2.2.4.1 14-1.2.2.1 15-1.2.2 16-1.2.2.2.r 17-1.2.2.2.r 18-1.2.2.2.1.1.1 20-1.2.2.2.2.1.1 22-1.2.2.2.3.1.1 23-1.2.2.2 26-1.3.1.1.1
These multiple Ras functions depend on its binding to a range of functionally diverse effector molecules such as Raf , PI3K , AF6 and RASSFs ( 1 ) .
SDL-AMR-09
Cancer
cancer
bio.mskcc_0001.21
Unlike WT B @-@ Raf , oncogenic B @-@ Raf proteins have been shown to heterodimerize constitutively with C @-@ Raf in a Ras @-@ independent manner ( 11 ) .
0-1.2.3.1 1-1.2.1.2 2-1.1.1.1.1 2-1.2.1.1.1 4-1.1.1.1.1 4-1.2.1.1.1 6-1.1.1 6-1.1.1.2 6-1.1.1.2.1.2.1 6-1.1.1.2.r 7-1.1.1.1.1 9-1.1.1.1.1 9-1.1.2.1.1 13-1.1.5 14-1.1.1 14-1.1.1.2 14-1.1.1.2.r 15-1.1 15-1.2 16-1.1.3 16-1.2.3 17-1.1.2.r 18-1.1.2.1.1 20-1.1.1.1.1 20-1.1.2.1.1 21-1.1.4.r 23-1.1.4.2.1.1 25-1.1.4 25-1.1.4.1 25-1.1.4.1.r 28-1.1.5.1.1.1
SDL-AMR-09
693
bio.bmtr_0002.1
Turke et al. “ MEK inhibition leads to PI3K @/@ AKT activation by relieving a negative feedback on ERBB receptors ” ( PMC3515079 )
SDL-AMR-09
0-1.2.1.1.1 1-1.2 2-1.2.2.1 4-1.3.1.1.1.1 5-1.3.1 6-1.3 7-1.3.2.r 8-1.3.2.1.1.1 10-1.3.2.1.1.1 11-1.3.2 12-1.3.3.r 13-1.3.3 15-1.3.3.2.1 16-1.3.3.2 17-1.3.3.2.1.1.r 18-1.3.3.2.1.1.1.1 19-1.3.3.2.1.1 22-1.1
3
BRAF
B-RAF
Aberle
alanine
GFAP
SDL-AMR-09
a_pmid_2488_5690.59
24885690
Flow cytometry revealed a significant increase of apoptotic cells in wild @-@ type compared to mutant clones upon withdrawal of serum ( Figure <xref ref-type="fig" rid="F2"> 2 </xref>@ F and G ) .
0-1.1.1.1 1-1.1.1.2 2-1 4-1.2.2 5-1.2 7-1.2.1.1 8-1.2.1 8-1.2.3 9-1.2.3.1.r 10-1.2.3.1 12-1.2.3.1 13-1.2.3.2.r 15-1.2.3.2.1 16-1.2.3.2 18-1.2.4 19-1.2.4.1.r 20-1.2.4.1 22-1.3.1.1 22-1.3.1.2 27-1.3.1
p
p2
Takeichi
16
28
78
79
SDL-AMR-09
RAF or MEK inhibitors induced luciferase activity of a HER3 promoter construct spanning ~ 1 kb upstream of the transcriptional start site in 8505C cells .
bio.bmtr_0003.7
0-1.1.1.1.1.1.1 1-1.1 2-1.1.2.1.1.1.1 3-1.1.1 3-1.1.1.1 3-1.1.1.1.r 3-1.1.2 3-1.1.2.1 3-1.1.2.1.r 4-1 5-1.2.2 6-1.2 7-1.2.1.r 9-1.2.1.1.1.1.1 10-1.2.1.1 11-1.2.1 12-1.2.1.2 13-1.2.1.2.2 14-1.2.1.2.2.1.1 16-1.2.1.2.1.2 19-1.2.1.2.1.1.1.1 20-1.2.1.2.1.1.1 21-1.2.1.2.1.1 22-1.2.1.2.3.r 23-1.2.1.2.3.1.1 24-1.2.1.2.3
0-1.1 0-1.3 3-1.1.1.1.1.1 4-1.1.1 5-1.1.1.2.1.1 6-1.1.2 10-1.1.2.1.1.1.1 12-1.1.2.1.2.1.1 14-1 14-1.2 14-1.2.r 15-1.3.r 17-1.3.1 19-1.3.1.1.1 20-1.3.1.1 21-1.3.1.1.2 23-1.4.1 29-1.5 32-1.5.1.r 33-1.5.1.1 34-1.5.1 35-1.5.1.1 36-1.1.2.1 36-1.3.1.1 38-1.5.1.2.2 39-1.5.1.2 40-1.5.1.2.1.r 41-1.5.1.2.1.1.1 42-1.5.1.2.3.r 43-1.5.1.2.3.1.1.1.1 44-1.5.1.2.3.1 45-1.5.1.2.3
bel_pmid_1064_0734.39828
SDL-AMR-09
Phosphorylation of both ERK1 and ERK2 induced by coligation of BCR and CD72 was weaker than that induced by BCR ligation alone ( Fig . 6 C ) , indicating that coligation with CD72 reduced BCR ligation @-@ mediated phosphorylation of ERK in DBA/2 spleen cells .
10640734
IGF-I
SDL-AMR-09
0-1.1 1-1 2-1.2.r 3-1.2.1 4-1.2 6-1.2.2.1 6-1.2.2.1.1 6-1.2.2.1.1.r 7-1.2.2 8-1.3.r 9-1.3.1.1 11-1.3.1 12-1.3.1.2.r 14-1.3.1.2.2.3.1 15-1.3.1.2.2.3.1 16-1.3.1.2.2.3.1 17-1.3.1.2.2.3.1 18-1.3.1.2.2.3.1 19-1.3.1.2.2.3.1 20-1.3.1.2.2.3.1 21-1.3.1.2.2.3.1 24-1.3.1.2.2.3 25-1.3.1.2.2.3.2.2 26-1.3.1.2.2.3.2.1.2.1.1 27-1.3.1.2.2.3.2.1 28-1.3.1.2.2.3.2 30-1.3.1.2 30-1.3.1.2.1 30-1.3.1.2.1.r 31-1.3.1.2.2 33-1.3.1.2.2.2.2 34-1.3.1.2.2.2.1 35-1.3.1.2.2.2.1 36-1.3.1.2.2.2.1 37-1.3.1.2.2.2 38-1.3 38-1.3.1.2.2.2.3 39-1.3.1.2.2.1.r 40-1.3.1.2.2.1.1.1 41-1.3.1.2.2.1 41-1.3.1.2.2.1.4 41-1.3.1.2.2.1.4.r 43-1.4.1 45-1.4.1.1
bio.chicago_2015.17703
We believe that it represents an unlikely scenario as we have shown that a PS1 allele defective in beta @-@ catenin binding , while retaining full Notch processing activity , cannot suppress the elevated beta @-@ catenin signaling caused by PS1 deficiency ( Fig . 4 ) .
6D
RKO
SDL-AMR-09
bio-kappa_0001.25
The mechanism of GEF action involves a series of fast reaction steps , which lead from a binary protein - nucleotide complex via a trimeric GNBP - nucleotide - GEF complex to a binary nucleotide - free complex , which is stable in the absence of nucleotide .
1-1.2 2-1.2.1.r 3-1.2.1.1.1.1 4-1.2.1 5-1 7-1.1 8-1.1.1.r 9-1.1.1.1 10-1.1.1.2 11-1.1.1 17-1.1.1.3.2.3 18-1.1.1.3.2.1 20-1.1.1.3.1.1.1 21-1.1.1.3.2 21-1.1.1.3.3 22-1.1.1.3.3.r 24-1.1.1.3.3.1 25-1.1.1.3.3.2.1.1 27-1.1.1.3.3.3 29-1.2.1.1.1.1 30-1.1.1.3.2 33-1.1.1.3.2.3 34-1.1.1.3.1.1.1 36-1.1.1.3.1.1 37-1.1.1.3.1 41-1.1.1.3.1.2 42-1.1.1.3.1.2.1.r 44-1.1.1.3.1.2.1 45-1.1.1.3.1.2.1.1.r 46-1.1.1.3.1.2.1.1
SDL-AMR-09
As predicted , only a very small fraction of wild @-@ type K @-@ Ras was pulled down by the GST @-@ RBD ( Fig . 2C and fig. S1D ) , consistent with very little wild @-@ type K @-@ Ras being in the GTP state under these conditions ( Fig.2 , A and B ) .
bio.bmtr_0001.19
1-1.3 3-1.1.3.2 5-1.1.3.1.1 6-1.1.3.1 7-1.1.3 8-1.1.3.r 9-1.1.2 11-1.1.2 12-1.1.1.1 14-1.1.1.1 16-1 17-1 18-1.2.r 20-1.2.1.1 22-1.2.1.1 24-1.4.1.1 26-1.4.1.1.1 27-1.4.1 28-1.4.1.1 28-1.4.1.2 28-1.5.1.4.1.1 28-1.5.1.4.1.2 29-1.4.1.2.1 32-1.5 34-1.5.1.1.2.1 35-1.5.1.1.2 36-1.5.1.1.3 37-1.5.1.1.3 38-1.5.1.1.3 39-1.1.1.1 39-1.5.1.1.1.1 41-1.1.1.1 41-1.5.1.1.1.1 45-1.5.1.2.1.1 48-1.5.1.3 49-1.5.1.3.r 54-1.4.1
677
threonine
PMC3651738
bio.chicago_2015.18911
0-1 2-1.1.1.1.1.1 5-1.1.1.2.1.1 6-1.1.3 7-1.1 8-1.1.2.1.1.1 9-1.1.2 10-1.1.2.2.r 11-1.1.2.2.2 12-1.1.2.2.1.1
However , caldesmon together with TM completely inhibits actin binding of human fascin .
SDL-AMR-09
CtBP2
-
d4
Engrailed
GDP
bio.mskcc_0001.6
SDL-AMR-09
Strikingly , the Raf proteins themselves are also substrates of activated ERK .
0-1.3 3-1.2.1.1 4-1.2 7-1.2.2 10-1.1.2 11-1.1.1.1
SDL-AMR-09
Moreover , given their constitutive phosphorylation on S/TP sites ( Fig . 3D ) , these oncogenic B @-@ Raf mutants were found to interact constitutively with Pin1 ( Fig . 7B ) , indicating that oncogenic B @-@ Raf proteins are dephosphorylated and recycled .
bio.mskcc_0001.45
0-1 4-1.1.1.6.1.2 5-1.1.1.6.1 8-1.1.1.6.1.1 10-1.1.1.6.1.3.1 12-1.1.1.6.1.3.1.1 15-1.1.1.1.4 16-1.1.1.1.3 16-1.1.1.1.3.1.2.1 17-1.1.1.1.1.1 19-1.1.1.1.1.1 20-1.1.1.1 20-1.1.1.1.2 20-1.1.1.1.2.r 22-1.1 23-1.1.1.1.3 23-1.1.1.6 24-1.1.1 25-1.1.1.3 26-1.1.1.2.r 27-1.1.1.2.1.1 29-1.1.1.4.1 31-1.1.1.4.1.1 34-1.1.1.5 36-1.1.1.1.3 36-1.1.1.1.3.1.2.1 36-1.1.1.6 37-1.1.1.6.1.1.1 38-1.1.1.6.1.1.1 39-1.1.1.6.1.1.1 40-1.1.1.6.1.1 42-1.1.1.5.1.1 43-1.1.1.5.1 44-1.1.1.5.1.2
-
Pin1
PKI166
septin
p4
LEF-1
bio.mskcc_0001.35
SDL-AMR-09
Examination of activated phospho @-@ MEK levels revealed that the FBm and S729 mutations had no effect on MEK activation induced by the high @-@ activity V600E B @-@ Raf protein ; however , the FBm and S729A mutations increased and decreased , respectively , the abilities of the intermediate G466A and kinase @-@ impaired D594G B @-@ Raf proteins to activate MEK ( Fig . 4B ) , indicating a correlation between the transformation potential of these proteins and their ability to activate ERK cascade signaling in vivo .
0-1.1 1-1.1.1.r 2-1.1.1.1.3 3-1.1.1.1.2 5-1.1.1.1.1.1 6-1.1.1 7-1 11-1.2.1.2 13-1.2.1.2.1 13-1.2.1.2.2 14-1.2.1.2.1.1.2 15-1.2.1.1 15-1.2.1.1.r 15-1.2.1.2.1.1.2.1 15-1.2.1.2.1.1.2.1.r 16-1.2.1 17-1.2.1.3.r 18-1.2.1.3.1.1.1 19-1.2.1.3 20-1.2.1.3.2 23-1.2.1.3.2.1.3.1 25-1.2.1.3.2.1.3 26-1.2.1.3.2.1.2.1 27-1.2.1.2.1.1.1.1 27-1.2.1.3.2.1.1.1 29-1.2.1.2.1.1.1.1 29-1.2.1.3.2.1.1.1 30-1.2.1.2.1.1.2.2 32-1.2 36-1.2.2.1.1 37-1.2.2.1.1.2.1 38-1.2.1.3.2.1 38-1.2.1.3.2.1.2 38-1.2.1.3.2.1.2.r 38-1.2.2.1.1.2 38-1.2.2.1.2.1.1.1 38-1.2.2.1.2.1.1.1.2 38-1.2.2.1.2.1.1.1.2.r 38-1.2.2.1.2.1.1.2 38-1.2.2.1.2.1.1.2.2 38-1.2.2.1.2.1.1.2.2.r 39-1.2.2.1 40-1.2.2 40-1.2.2.1.1 41-1.2.2.2 43-1.2.2.3 47-1.2.2.1.2.1.1.1.2.2.r 49-1.2.2.1.2.1.1.1.2.2 50-1.2.2.1.2.1.1.1.2.1 52-1.2.2.1.2.1.1.2.3.1 54-1.2.2.1.2.1.1.2.3 55-1.2.2.1.2.1.1.2.2.1 56-1.2.1.2.1.1.1.1 56-1.2.1.3.2.1.1.1 56-1.2.2.1.2.1.1.2.1.1 58-1.2.1.2.1.1.1.1 58-1.2.1.3.2.1.1.1 58-1.2.2.1.2.1.1.1.1.1 58-1.2.2.1.2.1.1.2.1.1 59-1.2.1.2.1.1.2.2 60-1.2.1.2.1.1.2.2.1.r 60-1.2.2.r 61-1.2.2.5.1.2.1 62-1.2.1.3.1.1.1 64-1.2.2.4.1 66-1.2.2.4.1.1 69-1.2.2.5 71-1.2.2.5.1 74-1.2.2.5.1.1.1 78-1.2.1.2.1.1.2.2 83-1.2.2.1.2.1 83-1.2.2.5.1.2.1 84-1.2.2.5.1.2.1.2.1.1.1 85-1.2.2.5.1.2.1.2.3 86-1.2.2.5.1.2.1.2 87-1.2.2.5.1.2.1.2.2 88-1.2.2.5.1.2.1.2.2
EGFR
HER2
1998
AF6
bel_pmid_1074_4722.15500
10744722
0-1 2-1.1.1.1 2-1.1.1.1.r 3-1.1.1.2 4-1.1.1 6-1.1 7-1.1.2.r 8-1.1.2.1.1 10-1.1.2.1.1 11-1.1.2 12-1.1.3 13-1.1.3.1.r 14-1.1.3.1.1 15-1.1.3.1 17-1.1.3.1.2.1.1.1 19-1.1.3.1.2.1 19-1.1.3.1.2.1.2 19-1.1.3.1.2.1.2.r 20-1.1.3.1.2.1.2.1.1.1.1 22-1.1.3.1.2.1.2.1.2.1.1 23-1.1.3.1.2 25-1.2.1.1 27-1.2.1.1.1 29-1.2.1.2.1 29-1.2.1.2.2 30-1.2.1.2.1.1 31-1.2.1.2 32-1.2.1.2.2.1
SDL-AMR-09
However , no such activation was found in A @-@ T cells indicating that caffeine inhibited the ATM @-@ dependent Chk2 @/@ Cds1 activation ( Fig . 3A , lanes 6 and 8 ) .
10640734
SDL-AMR-09
bel_pmid_1064_0734.39824
Western blotting of total cell lysates using anti @-@ phospho @-@ ERK Ab showed that both ERK1 and ERK2 were phosphorylated by either BCR ligation alone or coligation of BCR and CD72 ( Fig . 6B ) .
0-1.1 1-1.1 2-1.1.1.r 3-1.1.1.2 4-1.1.1.1 5-1.1.1 7-1.1.2.1 9-1.1.2.1.1.2 11-1.1.2.1.1.1.1 13-1 16-1.2.1.1.1.1 17-1.2.1 18-1.2.1.2.1.1 20-1.2 23-1.2.2.1.1.1.1 24-1.2.2.1 24-1.2.2.2 25-1.2.2.1.2 26-1.2.2 28-1.2.2.2.1.r 29-1.2.2.2.1 31-1.2.2.2.2.1.1 33-1.3.1 35-1.3.1.1
Dox
15280923
1-1.1.2 2-1.1.2.1.r 3-1.1.2.1.1.1 4-1.1.2.1 11-1.1.3 12-1.1 13-1.1.1.r 14-1.1.1 17-1.1.1.1.1 17-1.1.1.1.1.1 17-1.1.1.1.1.1.r 17-1.1.1.1.2 17-1.1.1.1.2.1 17-1.1.1.1.2.1.r 18-1.1.1.1.1.2 19-1.1.1.1 21-1.1.1.1.2.2 23-1 23-1.1.2.2.r 24-1.2.1 26-1.2.3 27-1.2 28-1.2.2.r 29-1.2.2 30-1.2.2.1 31-1.2.2.1.1.r 32-1.2.2.1.1.1.1.1.1 35-1.2.2.1.1 37-1.2.2.1.1.1.2.1.1
pmid_1528_0923.103
SDL-AMR-09
The proportion of SUM149 cells in G @<sub> 1 </sub> was significantly increased by treatment with either inhibitor alone and the combination , while apoptosis was significantly increased in cells exposed to PKI166 , with or without U0126 .
104
lysine
7E
HER3
B-Raf
T35
CTD-S2-P
Ras
338
brk
446
serine
27
BHA
-
ERBB3
10640734
SDL-AMR-09
0-1.2 1-1.1.2.2.2 3-1.1.1.2 4-1.1.1 4-1.1.1.1 4-1.1.1.1.r 5-1.1 9-1.1.2.2.1.1.1 10-1.1.2 11-1.1.2 12-1.1.2.1.1.2.1.1.1 14-1.1.2.1.1.2 15-1.1.2.1.1.1.1.1 16-1.1.2.1.1 17-1.1.2.1 19-1.1.2.1.2 20-1.1.2.3.r 21-1.1.2.3.2 22-1.1.2.3.3 23-1.1.2.3.1.1 24-1.1.2.3
Taken together , these results indicate that coligation with CD72 negatively regulates BCR @-@ induced ERK activation and Ca2+ concentration in normal spleen B cells .
bel_pmid_1064_0734.39832
-
Jak1
hairy
BRAF
1
K-Ras
PIK3CA
MEK
MDA-MB-468
-
SDL-AMR-09
bmtr_0007.6
Figure 1C shows that the phosphospecific antibody is specific for the ASPP2 fragment phosphorylated in vitro by MAPK .
0-1.1 1-1.1.1 2-1 6-1.2.1 8-1.2 8-1.2.1.1 9-1.2.2.r 11-1.2.2.1.1.1 13-1.2.1.1.1 13-1.2.2.2 14-1.2.2.2.2 15-1.2.2.2.2 16-1.2.2.2.1.r 17-1.2.2.2.1.1.1
-
to prevent the additional stabilization of U2AF65 binding conferred by the interaction between U2AF35 and the AG dinucleotide .
SDL-AMR-09
bio.chicago_2015.17446
1-1.1 3-1.1.1.2 4-1.1.1 5-1.1.1.1.r 6-1.1.1.1.1.1.1 7-1.1.1.1 8-1.1.1.1.2 9-1.1.1.1.2.1.r 11-1.1.1.1.2.1 13-1.1.1.1.2.1.1.1.1 16-1.1.1.1.2.1.2.1.1 17-1.1.1.1.2.1.2
-
HER2
0.01
CtBP1
CHO-KI
AMR-Concept
1128
SDL-AMR-09
The minimal HER3 promoter region regulated by MAPK inhibitors overlaps with sequences previously described to be immunoprecipitated using antibodies against the ZFN217 transcription factor and CtBP1 @/@ CtBP2 corepressors ( 28 @–@ 30 ) .
bio.bmtr_0003.11
1-1.1.1.2 2-1.1.1.1.1.1.1 3-1.1.1 3-1.1.1.1 3-1.1.1.1.r 4-1.1 5-1.1.2 6-1.1.2.1.r 7-1.1.2.1.1.1.1.1 8-1.1.2.1 8-1.1.2.1.1 8-1.1.2.1.1.r 9-1 10-1.2.r 11-1.2 12-1.2.1.2.1 13-1.2.1.2 13-1.3 16-1.2.1 17-1.2.1.1 18-1.2.1.1.1 19-1.2.1.1.1.1 21-1.2.1.1.1.1.1.1.1.1.1.1 22-1.2.1.1.1.1.1.1.1 23-1.2.1.1.1.1.1.1 24-1.2.1.1.1.1.1 25-1.2.1.1.1.1.1.2.1.1.1.1.1 27-1.2.1.1.1.1.1.2.1.1.2.1.1 30-1.3.1.1.1.1 32-1.3.1.1.1.2
CD72
TFIIH
1128
693
bio.mskcc_0001.41
1-1 3-1.1.1.1.1 3-1.1.1.1.2 3-1.1.1.1.3 3-1.1.1.1.4 5-1.1.1.1.1.1 7-1.1.1.1.2.1 9-1.1.1.1 10-1.1.1.1.3.1 11-1.1.1.1.4.1 14-1.1 16-1.1.1 17-1.1.1.2.1.1.1 19-1.1.1.2.1.1.1 20-1.1.1.2 22-1.1.1.3.1 24-1.1.1.3.1.1 28-1.1 29-1.1.2 30-1.1.2.1.r 31-1.1.2.1.1 32-1.1.2.1 33-1.1.2.1.2 37-1.1.2.1.2.1.3 40-1.1.2.1.2.1 43-1.1.2.1.2.1.1.1.1 46-1.1.2.1.2.1.2.1.1 48-1.1.2.1.2.1.1.1.1 48-1.1.2.1.2.1.2.1.1 51-1.1.2.1.3.1.1.1
In contrast , mutation of S151A , T401A , and S750A T753A were all found to increase C @-@ Raf binding ( Fig . 6A ) , a finding consistent with peptide studies suggesting that there are multiple points of contact between heterodimerized B @- and C @-@ Raf proteins ( 27 ) .
SDL-AMR-09
ERK
75
D594G
bio.chicago_2015.19058
0-1.1.1 1-1.1.1.1.r 2-1.1.1.1.1.1 3-1.1.1.1.1.2 4-1.1.1.1.1.3 5-1.1 7-1.1.2 8-1.1.2.1.r 9-1.1.2.1.1.1.1.1 10-1.1.2.1.1 11-1.1.2.1 12-1 13-1.2.1.1.1 14-1.2 19-1.2.2.1.1.1 20-1.2.2 21-1.2.2.2.1.1 23-1.2.3.r 25-1.2.3.1 27-1.2.3.1 29-1.2.3
Overexpression of cdc5 delta N induces a disturbance in septin ring structures and Cdc5 interacts with two septins , Cdc11 and Cdc12 , in a polo @-@ box - dependent manner .
SDL-AMR-09
1991
EGFR
Sorafenib
B-Raf
27
Chk2
Ras
ASPP2
GTPase
1-1 2-1 3-1.1.r 4-1.1.1.1.1 5-1.1.1.1.2 6-1.1.1.1.3 8-1.1.2.1.1 9-1.2.1.1 11-1.2.1.1 12-1.2.1.2 13-1.2.1.3
SDL-AMR-09
10842184
\" Negative regulation of growth hormone receptor @/@ JAK2 signaling by signal regulatory protein alpha.\"
bel_pmid_1084_2184.19138
-
HER2
tyrosine kinase Lyn
B-Raf
These results suggest that CBP can bind to various transcription factors of the ATF/ CREB family through the b @-@ ZIP domain .
0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 2-1 3-1.2.r 4-1.2.1.1.1.1 5-1.2 6-1.2.1 7-1.2.1.2.r 8-1.2.1.2.3 9-1.2.1.2.1 10-1.2.1.2 14-1.2.1.2.2.1.2 15-1.2.1.2.2 18-1.2.1.3.1.1 20-1.2.1.3.1.1
SDL-AMR-09
bio.chicago_2015.17757
Kamps
BRAF
-
S729A
oligodeoxynucleotide
beta-catenin
p2
315
serine
ERK12
n3
3F
GTP
TCF-1
T669A
15
12.453
bmtr_0007.2
A synthetic peptide encoding amino acids 824 @-@ 832 , with a phosphoserine at residue 827 , was used to raise antibodies .
1-1.1.1 2-1.1 3-1.1.2 4-1.1.2.1 5-1.1.2.1 6-1.1.2.1.1.1 8-1.1.2.1.1.2 14-1.1.2.1.2.1 15-1.1.2.1.2.1.1 18-1 20-1.2 21-1.2.1
SDL-AMR-09
104
lysine
MEK
27
GSK-3
cdk6
Given that oncogenic B @-@ Raf proteins are targets of feedback phosphorylation , we next examined whether they might also be dephosphorylated and recycled in a manner involving the PP2A phosphatase and the Pin1 prolyl @-@ isomerase .
2-1.3 2-1.3.1.2 2-1.3.1.2.2 2-1.3.1.2.2.1.2.1 2-1.3.1.2.2.r 3-1.3.1.2.1.1 5-1.3.1.2.1.1 8-1.3.1 9-1.3.1.1.r 10-1.3.1.1.1 11-1.3.1.1 13-1.1 14-1.4 15-1 16-1.2.1 16-1.2.1.r 18-1.2 19-1.2.2.3 21-1.2.2.1 22-1.2.2 23-1.2.2.2 24-1.2.2.r 26-1.2.2.4.r 27-1.2.2.4 29-1.2.2.4.1.1.1.1 30-1.2.2.4.1.1 31-1.2.2.4.1 33-1.2.2.4.1.2.1.1 34-1.2.2.4.1.2 36-1.2.2.4.1.2
SDL-AMR-09
bio.mskcc_0001.43
7
Pbx
BMP-2
FoxO
ABP
Ras
JAK2
21
SUM149
ADP
s
bel_pmid_1064_0734.39830
2-1.1.1.1.1 4-1.1.2.1.1 5-1 7-1.2.2 9-1.2 9-1.2.3 10-1.2.3.r 11-1.2.3.1 14-1.1.2.1.1 15-1.1 15-1.2.3.1.1 16-1.2.3.1.1.2 17-1.3.r 18-1.3.2 19-1.3.1.1 20-1.3 22-1.4.1 24-1.4.1.1
10640734
Coligation of CD72 with BCR showed a reduced Ca2+ flux compared to that with BCR ligation alone in spleen B cells ( Fig . 6D ) .
SDL-AMR-09
However , the CD72 transfectants showed less increase in the intracellular Ca2+ concentration than the parent K46^mA cells did .
10640734
0-1 3-1.1.1.1.1.1.1 4-1.1.1 4-1.1.1.1 4-1.1.1.1.r 5-1.1 6-1.1.2.2 7-1.1.2 8-1.1.2.1.r 10-1.1.2.1.2 12-1.1.2.1 13-1.1.2.3.r 15-1.1.2.3.2 16-1.1.2.3.1.1 17-1.1.2.3
SDL-AMR-09
bel_pmid_1064_0734.39818
0-1 1-1.1 3-1.1
SDL-AMR-09
Passage 1 @-@ 2 ( Discussion/Conclusion )
bio.bmtr_0004.16
1A
PKI166
bio.chicago_2015.18717
0-1.1.2 0-1.1.2.r 1-1.1 1-1.1.1 1-1.1.1.r 2-1 3-1.2.r 5-1.2.2.1.1 6-1.2.2.1 7-1.2.2 8-1.2.2.2 9-1.2.2.2.1.r 10-1.2.2.2.1.2 11-1.2.2.2.1.1.1.1 12-1.2.2.2.1 14-1.2 17-1.2.1.1.1 18-1.2.1
Our results demonstrate that the chromosome condensation defect caused by perturbed ISWI function is mediated through the NURF complex .
SDL-AMR-09
p62
4-hydroxytamoxifen
HEK293
2F
STAT3
2002
adenomatous polyposis coli
170
lysine
1987
n2
threonine
bio.mskcc_0001.7
2-1.2.1.1.2.r 3-1.2.1.1.1.1.1 5-1.2.1.1.1.1.1 7-1.2.1.2.1.1.1 9-1.2.1.2 10-1.2.1.1.2 11-1.2.1 14-1 15-1.2.1.1.2.r 16-1.2 18-1.2.2.1 19-1.2.2 21-1.2.2.2.2 22-1.2.2.2.2 23-1.2.2.2.2 24-1.2.2.2.2 25-1.2.2.2.2 26-1.2.2.2.2 27-1.2.2.2.2 28-1.2.2.2.2 29-1.2.2.2.2 30-1.2.2.2.2 31-1.2.2.2.2 32-1.2.2.2.1 34-1.2.2.2.3 37-1.2.2.2.3.1.1.2 38-1.2.2.2.3.1.1.1.1 40-1.2.2.2.3.1.1.1.1 43-1.2.2.2.3.1 48-1.2.2.2.1 53-1.2.2.2.3.1 55-1.2.2.2.3.1.3 56-1.2.2.2.3.1.3.1.1.1.1 57-1.2.2.2.3.1.3.1.1.1.2 58-1.2.2.2.3.1.3.1.1.1.3 62-1.2.2.2.3.1.3.1 64-1.2.2.2.3.1.3.1.2.1.1 65-1.2.2.2.3.1.3.1.2 67-1.2.2.2.3.1.3.1.2 69-1.1.1.1
SDL-AMR-09
In regard to C @-@ Raf , ERK @-@ dependent feedback phosphorylation has been shown to instigate a regulatory cycle whereby phosphorylation of the feedback sites down @-@ modulates C @-@ Raf signaling , after which the hyperphosphorylated C @-@ Raf protein is dephosphorylated and returned to a signaling @-@ competent state through dephosphorylation events involving protein phosphatase 2A ( PP2A ) and the Pin1 prolyl @-@ isomerase ( 8 ) .
58
59
CTBP
By definition , PLD catalyzes the hydrolysis of PC to PA and choline .
bio.chicago_2015.18689
SDL-AMR-09
1-1.3 3-1.1.1.1 4-1 6-1.2 7-1.2.1.r 8-1.2.1.1.1 9-1.2.2.r 10-1.2.2.1.1.1 11-1.2.2 12-1.2.2.2.1.1
368
372
1
bio.bel_0002.2
SDL-AMR-09
We show that wild @-@ type B @-@ RAF forms a complex with C @-@ RAF in a RAS @-@ dependent manner , whereas the mutants bind independently of RAS .
0-1.1 1-1 2-1.2.r 3-1.2.1.1.2 5-1.2.1.1.2 6-1.2.1.1.1.1 8-1.2.1.1.1.1 8-1.2.1.2.1.1 8-1.2.3.1.1.1.1 8-1.2.3.1.2.1.1 9-1.2 11-1.2.1 12-1.2.1.2.r 13-1.2.1.2.1.1 15-1.2.1.2.1.1 18-1.2.2.1.1.1 20-1.2.2 20-1.2.3.1.3 23-1.2.3 25-1.2.3.1.1 25-1.2.3.1.1.2 25-1.2.3.1.1.2.r 25-1.2.3.1.2 25-1.2.3.1.2.2 25-1.2.3.1.2.2.r 26-1.2.3.1 27-1.2.3.1.3.1 28-1.2.3.1.3.2.r 29-1.2.3.1.3.2
-
Dpp
B-Raf
-
4
p3
10000
AKT
-
1-1.1.1 2-1.1 3-1.1.2.r 4-1.1.2.1.1.1 6-1.1.2.1.1.1 7-1.1.2 10-1 11-1.2.r 13-1.2 13-1.2.1 13-1.2.1.r 15-1.2.2.r 16-1.2.2.1.1 21-1.2.3.1 22-1.2.3.1 23-1.2.3.1 25-1.2.3.2.1.1.1.1.1 27-1.2.3.2.1.1 28-1.2.3.2.1.1.2 29-1.2.3.2.1.1.2 31-1.2.3.2.1 32-1.2.3.2
A similar role in C @-@ Raf activation has been described for the catalytic subunit of PP1C , which associates with C @-@ Raf in Ras @- and growth factor - stimulated cells .
SDL-AMR-09
bio-kappa_0001.12
SDL-AMR-09
bio.bmtr_0002.16
Of note , this is the same EGFR @-@ mutant cell line in which we observed that EGFR T669 is phosphorylated in MEK @-@ dependent manner ( Figure 5 , Supplemental Figure 8A ) .
1-1 3-1.1.1 6-1.1 7-1.1.2.1.1.1 7-1.1.2.2.1.3.1.1 9-1.1.2.1 9-1.1.2.1.2 9-1.1.2.1.2.r 10-1.1.2 11-1.1.2 14-1.1.2.2.3.1 15-1.1.2.2.3 17-1.1.2.2.1.3.1.1 20-1.1.2.2 21-1.1.2.2.2.r 22-1.1.2.2.2.1.1.1 24-1.1.2.2.2 27-1.1.3.1.1 28-1.1.3.1.1.1 30-1.1.3.1.2.2 31-1.1.3.1.2 32-1.1.3.1.2.1
1
serine
p2
70
-
Consistent with this model , we found that when purified activated ERK was incubated with kinase @-@ dead B @-@ Raf( K375M ) in vitro , ERK strongly phosphorylated B @-@ Raf on the S151 , S750 , and T753 sites , with phosphorylation of T401 also observed ( Fig . 2B ) .
SDL-AMR-09
0-1.3 1-1.3.1.r 2-1.3.1.1 3-1.3.1 5-1.1 6-1 9-1.2.3.1 10-1.2.3.1 11-1.2.3.1 13-1.2.3 14-1.2.3.2.r 15-1.2.3.2.3.2 18-1.2.3.2.1.1 21-1.2.3.2.2.1 23-1.2.3.3 24-1.2.3.3 26-1.2.1.2.1.1 27-1.2.1.3 28-1.2.1 29-1.2.3.2.1.1 31-1.2.3.2.1.1 38-1.2 38-1.2.1.1 42-1.2.r 43-1.2.2 46-1.2.2.3.1 47-1.2.2.3 49-1.2.4.1 51-1.2.4.1.1
bio.mskcc_0001.16
2
cdc25A
3C
24885690
SDL-AMR-09
Consistent with data previously shown by others , starvation @-@ induced apoptosis is mediated by PUMA in a p53 @-@ independent fashion in our experiments [ @<xref ref-type="bibr" rid="B27"> 27 </xref>@ ] .
0-1.5 1-1.5.1.r 2-1.5.1 3-1.5.1.1.2 4-1.5.1.1 5-1.5.1.1.1.r 6-1.5.1.1.1.1 8-1.2.1.1 10-1.2.1 11-1.2 13-1 14-1.1.r 15-1.1.1.1 16-1.3.r 18-1.3.2.1.1 20-1.3 20-1.3.1 20-1.3.1.r 22-1.4.r 23-1.4.1 23-1.4.1.r 24-1.4 27-1.5.1.2.1.1.1
a_pmid_2488_5690.64
-
669
threonine
61L
NF1
C
Ras
extracellular signal-related kinase
30
29
27
w
K-Ras
MDA-MB-231
PI3K-C2beta
4-1.1.1 6-1.1.2 7-1.1 8-1 9-1.2 10-1.2.1 11-1.2.1.1.r 12-1.2.1.1.1.1 13-1.2.1.2.r 14-1.2.1.2.1.1 17-1.2.1.3.1.1.1 18-1.2.1.3.1.1.2 22-1.2.1.3 26-1.2.1.3.2.1.2 27-1.2.1.3.2.1.1
The switch - OFF process is entirely different and involves hydrolysis of GTP to GDP , the guanosine triphosphatase ( GTPase ) reaction , which is basically irreversible .
bio-kappa_0001.23
SDL-AMR-09
1
myosin
BRAF
As - catenin interacts with transcription factors of the LEF/ TCF family to regulate target gene expression , this raises the possibility that nuclear events of Wnt/ - catenin signaling are involved in regulating convergent extension .
2-1.1.1.1 3-1 4-1.2.r 5-1.2.1 6-1.2 10-1.2.2.1.2 11-1.2.2 13-1.3 14-1.3.2.1.1 15-1.3.2.1 16-1.3.2 19-1.4 21-1.4.1 22-1.4.1.1.r 23-1.4.1.1.1.1 24-1.4.1.1.1 28-1.4.1.1.1.2.1.1.1.1 29-1.4.1.1.1.2.1 31-1.4.1.1 32-1.4.1.1.2.r 33-1.4.1.1.2 34-1.4.1.1.2.2.1 35-1.4.1.1.2.2
SDL-AMR-09
bio.chicago_2015.17666
GST
mRNA
0-1.1.1.1.1.2.1 1-1.1 2-1.1.2.1.1.2.1 3-1.1.1 3-1.1.1.1 3-1.1.1.1.r 3-1.1.2 3-1.1.2.1 3-1.1.2.1.r 4-1 5-1.2.2 6-1.2 7-1.2.1.r 9-1.2.1.1.1.2.1 10-1.2.1.1 11-1.2.1 12-1.2.1.2 13-1.2.1.2.3 14-1.2.1.2.3.1.1 16-1.2.1.2.1.2 19-1.2.1.2.1.1.1.1 20-1.2.1.2.1.1.1 21-1.2.1.2.1.1 22-1.2.1.2.2.r 23-1.2.1.2.2.2.1 24-1.2.1.2.2
SDL-AMR-09
bio-exp_0001.6
RAF or MEK inhibitors induced luciferase activity of a HER3 promoter construct spanning ~ 1 kb upstream of the transcriptional start site in 8505C cells .
e
2
IGF-I
We measured the rate of GAP @-@ mediated GTP hydrolysis and observed that the response of Ras ligated to Ubiquitin @-@ C77 was identical to Ras ligated to Ubiquitin @-@ G76C ( Fig . 5b ) .
SDL-AMR-09
bio.bmtr_0004.10
0-1.1.1 1-1.1 3-1.1.2 4-1.1.2.1.r 5-1.1.2.1.2.1.1.1 7-1.1.2.1.2 8-1.1.2.1.1.1.1 9-1.1.2.1 10-1 11-1.2 12-1.2.2.r 14-1.2.2.1 14-1.2.2.1.1 14-1.2.2.1.1.r 14-1.2.2.2 14-1.2.2.2.1 14-1.2.2.2.1.r 16-1.2.2.1.1.1.1.1 16-1.2.2.2.1.1.1.1 17-1.2.2.1.1.1.2 17-1.2.2.2.1.1.2 19-1.2.2.1.1.1.2.1.3.1.1 19-1.2.2.2.1.1.2.1.3.1.1 23-1.2.2 25-1.2.2.1.1.1.1.1 25-1.2.2.2.1.1.1.1 26-1.2.2.1.1.1.2 26-1.2.2.2.1.1.2 28-1.2.2.1.1.1.2.1.3.1.1 28-1.2.2.2.1.1.2.1.3.1.1 30-1.2.2.2.1.1.2.1.3.2.1 32-1.2.2.3.1 34-1.2.2.3.1.1
GSK-3beta
PLX4032
1997
4
bio.chicago_2015.18258
1-1 4-1.1.1.3.1.2.1.1 5-1.1.1.3.1 7-1.1.1 7-1.1.1.2 7-1.1.1.2.1 7-1.1.1.2.1.r 7-1.1.1.2.r 9-1.1.1.2.2 12-1.1.1.1.1 14-1.1.1.1.1 16-1.1.1.1.1 17-1.1 18-1.1.2.1.1.1 19-1.1.2 20-1.1.2.2.r 21-1.1.2.2.1.1 23-1.1.3.1 25-1.1.3 27-1.1.4 28-1.1.4.1.r 29-1.1.4.1.1.1.1 30-1.1.4.1 31-1.1.4.1.2.r 33-1.1.4.1.2.2 34-1.1.4.1.2.1 35-1.1.4.1.2 36-1.1.4.1.3.r 37-1.1.4.1.3.2.1 39-1.1.4.1.3.2 40-1.1.4.1.3 41-1.1.3 41-1.1.4.1.3.1.r 42-1.1.4.1.3.1
In contrast , the ATP binding @-@ deficient , dominant @-@ negative HA @-@ MEKK1 @-@ K1255M reduced Axin activation of JNK by 3 @-@ fold , suggesting that MEKK1 acts in the same signaling pathway in Axin @-@ mediated activation of JNK .
SDL-AMR-09
p
10644693
Furthermore , the hCdc14 phosphatases were found to dephosphorylate p53 specifically at the p34( Cdc2 ) / clb phosphorylation site ( p53 @-@ phosphor @-@ Ser( 315 )) .
SDL-AMR-09
bel_pmid_1064_4693.7794
0-1 3-1.1.1.2.1.1 4-1.1.1.2.1.2 6-1.1 8-1.1.1 9-1.1.1.1.3.1.1 10-1.1.1.3 17-1.1.1.1.1.1.1.1 18-1.1.1.1.1 19-1.1.1.1 21-1.1.1.1.2.1.4 26-1.1.1.1.2.1.1
First , PR facilitates binding of NF1 by an ATP @-@ dependent process that results in marked reduction of the linking number of chromosomal DNA .
SDL-AMR-09
0-1.3 2-1.1.1.1 3-1 4-1.2 5-1.2.2.r 6-1.2.2.1.1 7-1.2.1.r 9-1.2.1.1.1.1.1 11-1.2.1.1 12-1.2.1 14-1.2.1.2 15-1.2.1.2.1.r 16-1.2.1.2.1.2 17-1.2.1.2.1 18-1.2.1.2.1.1.r 20-1.2.1.2.1.1.1 21-1.2.1.2.1.1 22-1.2.1.2.1.1.2.r 23-1.2.1.2.1.1.2.2 24-1.2.1.2.1.1.2.1.1
bio.chicago_2015.18265
However , our results provide the first direct evidence for a protein that may stabilize nucleotide @-@ free Ras in vivo .
bmtr_0006.5
SDL-AMR-09
0-1 2-1.1.1.2 2-1.1.1.2.r 3-1.1.1 3-1.1.1.1 3-1.1.1.1.r 4-1.1 6-1.1.2.2 6-1.1.2.2.1 6-1.1.2.2.1.r 7-1.1.2.1 8-1.1.2 9-1.1.2.3.r 11-1.1.2.3 13-1.1.2.3.1.2 14-1.1.2.3.1 15-1.1.2.3.1.1.2.1 17-1.1.2.3.1.1 17-1.1.2.3.1.1.2 17-1.1.2.3.1.1.2.r 18-1.1.2.3.1.1.1.1 19-1.1.2.3.1.3 20-1.1.2.3.1.3
pmid_1528_0923.99
SDL-AMR-09
15280923
Apoptosis induced by PKI166 and U0126 was assessed by measuring DNA fragmentation by propidium iodide staining and FACS analysis , and determining the proportions of hypodiploid cells .
0-1.2 1-1.2.1 2-1.2.1.1.r 3-1.2.1.1.1.1.1 4-1.2.1.1 5-1.2.1.1.2.1.1 7-1 8-1.1.r 9-1.1.1 10-1.1.1.1.2.2.1 10-1.1.1.1.2.3.1 11-1.1.1.1 12-1.1.1.1.1.r 13-1.1.1.1.1.1.1.1.1 14-1.1.1.1.1.1.1.1.2 15-1.1.1.1.1.1 16-1.1.1.1.1 17-1.1.1.1.1.2.1.1.1 18-1.1.1.1.1.2 20-1.1 21-1.1.2 23-1.1.2.1 24-1.1.2.1.1.r 25-1.1.2.1.1.1 26-1.1.2.1.1
pmid_1528_0923.97
0-1.1 2-1.1.1.1.1 4-1.1.1.1.1 6-1.1.1.1.1 7-1.1.1 8-1.1.2.r 9-1.1.2.1.1 10-1.1.2.2 11-1 12-1.2.1.1 13-1.2.1 14-1.2 18-1.3.1.r 19-1.3.3 20-1.3 20-1.3.1 20-1.3.1.r 21-1.3.2.r 22-1.3.2.1 23-1.3.2
SDL-AMR-09
Treating the MDA @-@ MB @-@ 231 cells with U0126 alone produced 8.5 % inhibition , which was not significantly different from control values .
15280923
colorectal cancer
Colorectal_cancer
Chk1
1-1
GTP
p2
a2
SDL-AMR-09
Previous studies have found that all oncogenic B @-@ Raf proteins can activate C @-@ Raf and that heterodimerization with C @-@ Raf is required for kinase @-@ impaired oncogenic B @-@ Raf proteins to mediate ERK activation in vivo ( 31 ) .
0-1.1.1 1-1.1 3-1 4-1.2.r 5-1.2.1.1.1.2 6-1.2.1.1.1 6-1.2.1.1.1.3 6-1.2.1.1.1.3.1.2.1 6-1.2.1.1.1.3.r 7-1.2.1.1.1.1.1 9-1.2.1.1.1.1.1 9-1.2.1.1.2.1.1 11-1.2.1 12-1.2.1.1 13-1.2.1.1.2.1.1 15-1.2.1.1.1.1.1 15-1.2.1.1.2.1.1 16-1.2 17-1.2.r 18-1.2.2.2 19-1.2.2.2.2.r 20-1.2.2.2.2 22-1.2.1.1.1.1.1 22-1.2.1.1.2.1.1 22-1.2.2.1.1.1.1 24-1.2.2 28-1.2.2.1.1.3.2 29-1.2.2.1.1.2 30-1.2.1.1.1.1.1 32-1.2.1.1.1.1.1 34-1.2.1.1.1 34-1.2.1.1.1.3 34-1.2.1.1.1.3.r 35-1.2.2.1 36-1.2.2.1.2.1.1.1 37-1.2.2.1.1 37-1.2.2.1.1.3 37-1.2.2.1.1.3.r 37-1.2.2.1.2 38-1.2.2.1.2.2 39-1.2.2.1.2.2 41-1.3.1.1.1
bio.mskcc_0001.27
GTP
Extradenticle
PKC
STAT3
Matrigel
ES1
SRC-1
RAS
RBD
cdk4
Serine
serine
-
MDA-MB-231
10851055
SDL-AMR-09
0-1.1.2.1.1.1 2-1.1.2.1.1.1 4-1.1.2 9-1.1.1.1 9-1.1.1.1.r 10-1.1.1 11-1 13-1.2.2 14-1.2 15-1.2.1.r 17-1.2.1.1 18-1.2.1.1.1.r 19-1.2.1.1.1.1.1 20-1.2.1 21-1.2.1.2 24-1.2.1.2.1.1.1.1 25-1.2.1 26-1.2.1.2.1.2
bel_pmid_1085_1055.19244
IL @-@ 2 @-@ mediated hetero @-@ dimerization of its receptor triggers a rapid increase in the recruitment of Jak3 and activation of both Jak1 and Jak3
1-1.1 2-1.1 3-1.1.1.r 4-1.1.1.1.1.1 5-1.1.1 6-1.1.2.r 7-1.1.2.1.1.1 8-1.1.2 9-1 11-1.2.1 12-1.2 13-1.2.2.r 14-1.2.2.1 15-1.2.2 16-1.2.2.2 17-1.2.2.2.1.r 19-1.2.2.2.1 20-1.2.2.2.1.1.r 22-1.2.2.2.1.1.2 23-1.2.2.2.1.1.2.1.1 26-1.2.2.2.1.1.3.r 29-1.2.2.2.1.1.3.2 30-1.2.2.2.1.1.3.2.1.1 32-1.2.2.2.1.1.1 33-1.2.2.2.1.1 33-1.2.2.2.1.1.3
The negative regulation of brinker expression by Dpp signaling illustrates a significant element of regulatory versatility afforded by the use of a Type II , as compared with a Type I , switch mechanism .
bio.chicago_2015.18666
SDL-AMR-09
Cds1
Ras
NF-kB
HER2
B-Raf
Sur-8
K46^mA
bcl-2
IL-6
M1
Huang
-
MDA-MB-231
MEK
Cdc25C
bio-kappa_0001.2
SDL-AMR-09
Of the three Raf kinases , only B @-@ Raf is able to function as an allosteric activator in the context of the Raf heterodimers , a role independent of B @-@ Raf kinase activity .
2-1.1.1.2.1.1 3-1.1.1.2.1.2.1 4-1.1.1 4-1.1.1.2.1 6-1.1.1.3 7-1.1.1.1.1 9-1.1.1.2.1.2.1 9-1.1.3.1.1.1.1 11-1 16-1.1.2 17-1.1 23-1.1.1.2.1.2.1 23-1.1.3.1.1.1.1 24-1.1.3.1 28-1.1.4 28-1.1.4.1 28-1.1.4.1.r 29-1.1.4.2.r 30-1.1.4.2.1 31-1.1.4.2.1 32-1.1.4.2.1 33-1.1.4.2.1 34-1.1.4.2
IGF-I
JAK1
Ras
19
B-Raf
ERBB3PI3KAKT
2
Notch
U0126
SUM149
10729607
bel_pmid_1072_9607.31242
transforming growth factor @-@ b2 ( TGF @-@ b2 ) was shown to upregulate the transcription rate of PAFR transcript 1 in Ramos human lymphoblastoid cells
SDL-AMR-09
0-1.1.2.1.1 1-1.1.2.1.2 2-1.1.2.1.3 4-1.1.2.1.3 4-1.1.2.2.1.1.1 6-1.1.2.2.1.1.1 8-1.1.2.1.3 8-1.1.2.2.1.1.1 11-1 13-1.1 15-1.1.1.1 16-1.1.1 17-1.1.1.1.1.r 18-1.1.1.1.1.1.1 19-1.1.1.1.1.1.2 20-1.1.1.1.1.1.3 21-1.1.3.r 22-1.1.3.1.1 23-1.1.3.1.2 24-1.1.3.1.3 25-1.1.3
0-1 2-1.1.1.1.1.1 3-1.1.1.1 4-1.1.1 5-1.1 6-1.1.2.1.1 7-1.1.2 9-1.1.3.r 11-1.1.3.1.1 12-1.1.3.1 13-1.1.3 16-1.1.3.2
bio.bmtr_0005.23
SDL-AMR-09
Additionally , RAS/Raf/MAPK pathway activation stabilizes ASPP2 protein , although the underlying mechanism remains to be investigated .
S1C
2
serine
RAF
PKI166
12
13
15
RKO
PS1
e
10729607
SDL-AMR-09
bel_pmid_1072_9607.19490
0-1.1.1.1 1-1 2-1.2.1.1.1.1 3-1.2.1 4-1.2 5-1.2.2 6-1.2.2.1.r 7-1.2.2.1.1.1 8-1.2.2.1.1.2 9-1.2.2.1.1.3 13-1.3.r 14-1.3.2 15-1.3.1 16-1.3 17-1.3.3 18-1.3.3.1.r 19-1.3.3.1.2 20-1.3.3.1.1 21-1.3.3.1
PAF induced tyrosine phosphorylation and activation of focal adhesion kinase ( FAK ) in human endothelial cells derived from vein umbilical cord
PUMA
bio-exp_0001.1
We next examined the mechanisms accounting for the increase in HER3 by MAPK pathway inhibitors in BRAF mutant thyroid cell lines .
SDL-AMR-09
0-1.1 1-1.3 2-1 4-1.2 5-1.2.1 6-1.2.1.1.r 8-1.2.1.1 9-1.2.1.1.2.r 10-1.2.1.1.2.1.1 11-1.2.1.1.1.r 12-1.2.1.1.1.1.1.1.1 13-1.2.1.1.1.1.1 14-1.2.1.1.1 14-1.2.1.1.1.1 14-1.2.1.1.1.1.r 15-1.2.1.1.1.1.2.r 16-1.2.1.1.1.1.2.2.1.3.1.1 17-1.2.1.1.1.1.2.2.1.3 17-1.2.1.1.1.1.2.2.1.3.2 17-1.2.1.1.1.1.2.2.1.3.2.r 18-1.2.1.1.1.1.2.1 19-1.2.1.1.1.1.2 20-1.2.1.1.1.1.2
Axin
ZNF217
5
mRNA
1
SDL-AMR-09
2-1.2.3.2.1.1.1 6-1.2.3.2.2.1.1 7-1.2.3.2 8-1.2.3.2 9-1.2.3.1 11-1.2.3.1 13-1.1 14-1 17-1.2.2 19-1.2 22-1.2.1 22-1.2.2.2 23-1.2.1.1.r 23-1.2.2 24-1.2.1.1.1.1.1 25-1.2.1.1 27-1.2.1.1.1.2.1.2 27-1.2.1.1.1.2.1.2.1 27-1.2.1.1.1.2.1.2.1.r 28-1.2.1.1.1.2.1.1.1 32-1.2.2.2.1 33-1.2.2.2 34-1.2.2.2.2.r 35-1.2.2.2.2.1.1.1 36-1.2.2.2.2
bio.bmtr_0004.5
At a GAP @-@ to @-@ Ras ratio of 1 @:@ 500 , we observed an order of magnitude increase in the rate of GTP hydrolysis for unmodified Ras relative to the intrinsic rate of GTP hydrolysis .
ERK
serine
151
24
0-1.2.3.2.1.2.1 1-1.1.1 1-1.1.1.r 2-1.1 3-1 5-1.2.1.1 6-1.2.1 7-1.2 8-1.2.2.r 9-1.2.2.1.1.1 10-1.2.2 13-1.2.3.1 15-1.2.3 19-1.2.3.2 20-1.2.3.2.1.r 21-1.2.3.2.1.1.1 22-1.2.3.2.1.1 23-1.2.3.2.1 25-1.2.3.2.1.2
Thus our work establishes an entirely new mode of Ras activation in which signaling is sustained even in the absence of hormone stimulus or oncogene mutation .
bio.bmtr_0004.27
SDL-AMR-09
66
77
cysteine
8
1A
SDL-AMR-09
We demonstrate that the RBD of PI3KC2β binds nucleotide @-@ free Ras in vitro ( Fig . 5 ) .
0-1.1 1-1 2-1.2.r 4-1.2.1.1.1 6-1.2.1.2.1.1 7-1.2 8-1.2.2.2.1 10-1.2.2 10-1.2.2.2 10-1.2.2.2.r 11-1.2.2.1.1 12-1.2.3 13-1.2.3 15-1.3.1 17-1.3.1.1
bmtr_0006.6
B-Raf
B-Raf
-
Ras
DNA
DNA
e2
PLX4032
M1
EGFR
5B
C-terminus
H-Ras
750
serine
w2
HER2
MAPK
bio.bmtr_0005.8
1-1.1.1.1.1.1 2-1.1.1 3-1.1 4-1.1 5-1.1.2.1 5-1.1.2.2 5-1.2.2.2 6-1.1.2.1.1.1 7-1.1.2 8-1.1.2.2.1.1 10-1.1.2 12-1.2.1.1.1.1 13-1.1.1 13-1.2.1 14-1.1 14-1.2 15-1.1 16-1.2.2.1 17-1.2.2.1.1.1 18-1.2.2 19-1.2.2.2.1.1 21-1.3.1 22-1.3.1.1
SDL-AMR-09
The ASPP1 sites are at residues 671 and 746 , and the ASPP2 sites are at residues 698 and 827 ( Figure 1A ) .
prefoldin
These interactions are specific , because an E1A polypeptide that binds to the ASH1 binding region in dCBP blocks the GST @-@ ASH1( 47 @-@ 456 )- dCBP interaction more efficiently than an E1A @-@ RG2 polypeptide that carries a mutation that reduces E1A binding to dCBP ( Fig . 7E ) .
SDL-AMR-09
0-1.1.1 1-1.1 3-1 5-1.2 7-1.2.1.1.1.1.1 8-1.2.1.1 10-1.2.1.1.2 11-1.2.1.1.2.1.r 13-1.2.1.1.2.1.1.1.1.1 14-1.2.1.1.2.1.1 15-1.2.1.1.2.1 16-1.2.1.1.2.1.2.r 17-1.2.1.1.2.1.2.1.1 18-1.2.1 20-1.2.1.2.1.1.1 23-1.2.1.2.2.1.1.1 25-1.2.1.2.2.1.1.2 27-1.2.1.2.2.2 28-1.2.1.2 29-1.2.1.3.1 30-1.2.1.3 31-1.2.1.3.2.r 33-1.2.1.3.2.1.1.1 35-1.2.1.3.2.1.1.1 36-1.2.1.3.2 38-1.2.1.3.2.2 40-1.2.1.3.2.2.1 42-1.2.1.3.2.2.1.1 43-1.2.1.3.2.1.1.1 44-1.2.1.3.2.2.1.1.1 45-1.2.1.3.2.2.1.1.1.2.r 46-1.2.1.3.2.2.1.1.1.2 48-1.3.1 50-1.3.1.1
bio.chicago_2015.18552
-
stauro
Chk2
p3
NGF
1-1.1.1 2-1.1.1.1.r 3-1.1.1.1.4 4-1.1.1.1.1 5-1.1.1.1 8-1.1.1.1.2 9-1.1.1.1.2.1.r 10-1.1.1.1.2.1.1.1 13-1.1.1.1.3 14-1.1.1.1.3.1.r 16-1.1.1.1.3.1.1.1 19-1.1.1.1.3.1.2.1.1.1.1 20-1.1.1.1.3.1.2 20-1.1.1.1.3.1.2.1 20-1.1.1.1.3.1.2.1.r 22-1.1.1.1.3.1.2.2.r 23-1.1.1.1.3.1.2.2.r 24-1.1.1.1.3.1.2.2.1.1.1 24-1.1.1.1.3.1.2.2.2.1.1 26-1.1.1.1.3.1.2.2.1.1.1 27-1.1.1.1.3.1.2.2 28-1.1.1.1.3.1.2.2.1.1.1 28-1.1.1.1.3.1.2.2.2.1.1 30-1.1.1.1.3.1.2.2.2.1.1 32-1 33-1.1.3 35-1.1 36-1.1.2.r 37-1.1.2.1.1.1 39-1.1.2.1.1.1 40-1.1.2 41-1.1.2.2.r 42-1.1.2.2.1.1.1 43-1.1.2.2.1 44-1.1.2.2
SDL-AMR-09
The role of other transcription factors that are regulated by PKA and that bind to the CRE of the fibronectin promoter , such as ATF @-@ 1 and ATF @-@ 2 , may also be relevant to TGF @-@ beta stimulation of fibronectin gene transcription .
bio.chicago_2015.17923
0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 3-1 4-1.2 5-1.2.1 6-1.2.1.1.r 8-1.2.1.1.2.1.1.1 9-1.2.1.1 9-1.2.1.1.2 9-1.2.1.1.2.r 10-1.2.1.1.1.1 12-1.1.3.1 12-1.1.3.1.r 13-1.1.3
Similar results were found following treatment with the MEK inhibitor AZD6244 ( not shown ) .
bio-exp_0001.4
SDL-AMR-09
GTP
SDL-AMR-09
0-1.2 2-1 3-1.1.r 5-1.1.2 6-1.1.2 7-1.1 9-1.1.1.1.1.1.1.1 10-1.1.1.1.1 11-1.1.1.1.1.2.2.1.1.1 14-1.1.1.1.1.2.1.3.1.1 16-1.1.1.1.1.2.2 17-1.1.1.1.1.2 18-1.1.1.1.1.2.1.r 19-1.1.1.1.1.2.1.1.1.1 21-1.1.1.1.1.2.1.2.1.1 23-1.1.1.1.1.2.1 24-1.1.1.1.1.2.1.3.1.1 26-1.1.1.1.1.2.1.3.1.1 27-1.1.2 29-1.1.1.1.1.2.1.4.1 30-1.1.1.1.1.2.1.4 32-1.1.1.1 34-1.1.1.1.2.2 36-1.1.1.1.1.2.2.1.1.1 39-1.1.1.1.1.2.1.3.1.1 41-1.1.1.1.1.2.1.3.1.1 43-1.1.1.1.1.2.1.3.1.1 46-1.1.1.1.1.2.1.2.1.1 48-1.1.1.1.1.2.1.1.1.1 50-1.1.1.1.2.1 50-1.1.1.1.2.1.r 51-1.1.1.1.2 54-1.1.1.r 55-1.1.1.2.2 57-1.1.1.2.1 57-1.1.1.2.1.r 58-1.1.1.2 59-1.1.1.1.1.2.2.1.1.1 62-1.1.1.1.1.2.1.3.1.1 63-1.1.1.2.3 65-1.1.1.2.3.2 67-1.1.1.2.3.2.1.1 68-1.1.1.2.3.2.1 70-1.3.1.1.1.1 72-1.3.1.1.1.2
bio.chicago_2015.18159
This is supported by the in vitro observations that Dvl inhibits GSK @-@ 3 beta @-@ dependent phosphorylation of Axin , APC , and beta @-@ catenin in the Axin complex , although the bindings of GSK @-@ 3 beta , beta @-@ catenin , and APC to Axin are not changed , and that Dvl does not affect GSK @-@ 3 beta activity to phosphorylate the peptide substrate ( 22 , 26 ) .
3
p3
serine
EGFR
EGFR
GTPase
p2
-
SDL-AMR-09
10677502
p44MAPK @/@ extracellular signal @-@ regulated kinase 1 ( ERK1 ) and p42 MAPK @/@ ERK2 are activated by IL @-@ 3 , colocalize with mitochondrial Bcl2 , and can directly phosphorylate Bcl2 on Ser @-@ 70 in a stauro @-@ resistant manner both in vitro and in vivo
0-1.1.2.1.1.1 2-1.1.2.1.2.1.1.1 3-1.1.2.1.2.1.1.2 5-1.1.2.1.2.1.1.2 6-1.1.2.1.2.1.1.3 7-1.1.2.1.2.1.1.4 9-1.1.2.1.2.1.2.1.1.1 11-1.1.2 15-1.1.2.2.2.1.1.1 17-1.1 18-1.1.1.r 19-1.1.1.1.1 21-1.1.1.1.1 23-1.2 26-1.2.1.2.1.1 28-1 28-1.2.1 29-1.3 30-1.3.1.5 31-1.3.1 32-1.3.1.1.3 34-1.3.1.1.2.1 36-1.3.1.1.1 37-1.3.1.3.r 37-1.3.1.4.1 39-1.3.1.3.1.1.1 41-1.3.1.3 42-1.3.1.4.r 44-1.3.1.4.1 45-1.3.1.4.1 46-1.3.1.4 47-1.3.1.4.1 47-1.3.1.4.2 48-1.3.1.4.2
bel_pmid_1067_7502.21952
5E
C-Raf
bio.mskcc_0001.29
SDL-AMR-09
For these studies , FBm or S729A mutations were incorporated into a number of oncogenic B @-@ Raf proteins that exhibit various levels of kinase activity .
1-1.3.1 2-1.3 5-1.1 6-1.1.2.2.1 7-1.1.1 7-1.1.1.2 7-1.1.1.2.r 7-1.1.2 7-1.1.2.2 7-1.1.2.2.r 9-1 9-1.1.1.3.1 10-1.1.1.3.2.1.r 10-1.2.r 12-1.2.3 13-1.2.3.r 14-1.2 14-1.2.2 14-1.2.2.1.2.1 14-1.2.2.r 15-1.1.1.1.1 15-1.1.2.1.1 15-1.2.1.1 17-1.1.1.1.1 17-1.1.2.1.1 17-1.2.1.1 18-1.1.1.3.2 20-1.2.4 21-1.2.4.1.1 22-1.2.4.1 23-1.2.4.1.2.r 24-1.2.4.1.2.1 25-1.2.4.1.2
ERK12
e
C-Raf
ERBB3
729
serine
B-RAF
Gly12
ERK
ASPP2
Urano
MEK
FoxO
ASPP2
Ras
PDGFR-B
CD72
1-1
e3
401
threonine
ERK
STAT
1
8505C
ASPP2
Rad
GI101A
c
50
interrogative
FGFR3
EGFR
HER3
PLD
HER2
27
3-1.3 4-1.3.2 7-1.1.1.1.1.1 7-1.2.1.1.1.1.1 9-1.1.1.1.2 11-1.1.1.1.2 12-1.1.1 13-1.1 14-1.1.2.1.1.1 15-1.1.2 16-1.1.3.r 17-1.1.3 18-1 20-1.2.1.1.1.1.1 23-1.2.1.1.1 23-1.2.1.1.1.2 23-1.2.1.1.1.2.r 24-1.2.1 25-1.2.1.1 26-1.2 27-1.2.2 28-1.2.3.r 29-1.2.3.1 31-1.2.3.1.1 32-1.2.3 35-1.3.1.1.1
SDL-AMR-09
a_pmid_2488_5690.52
24885690
It has been shown previously that <i> BRAF </i> wild @-@ type cells require glucose supply for survival whereas <i> BRAF </i>@ -@ mutant cell clones maintain proliferation in low @-@ glucose environments [ @<xref ref-type="bibr" rid="B20"> 20 </xref>@ ] .
SH2 domain
p
4B
e3
Similar to the MTT results in <xref ref-type="table" rid="tbl1"> Table 1 </xref> , SKBR3 and SUM 149 cells were most sensitive to treatment with the inhibitors , while the proportions of hypodiploid MDA @-@ MB @-@ 231 cells were lower .
SDL-AMR-09
15280923
pmid_1528_0923.101
0-1.3 1-1.3.1.r 3-1.3.1.1.1.1.1 4-1.3.1 4-1.3.1.1 4-1.3.1.1.r 7-1.3.1.2 8-1.3.1.2.1 11-1.1.1.1.1.1 12-1.1.1 15-1.1.1.1 15-1.1.1.2 17-1.1.3 18-1.1 19-1.1.2.r 20-1.1.2 21-1.1.2.2.r 23-1.1.2.2 23-1.1.2.2.1 23-1.1.2.2.1.r 25-1 27-1.2.1 28-1.2.1.1.r 29-1.2.1.1.2 30-1.2.1.1.1.1 32-1.2.1.1.1.1 34-1.2.1.1.1.1 35-1.2.1.1 37-1.2 37-1.2.2 37-1.2.2.r
4.5
1-1.3 2-1.3.1.r 3-1.3.1 4-1.3.1.1 6-1.1.1.1.1 7-1.1 8-1 9-1.2.2.1.1.1.1 10-1.2.2.1 11-1.2.2.1.2.1.1 12-1.2.1.1 13-1.4.r 14-1.4.2.2 15-1.4.2.1.1 16-1.4.1.1.3.1.1 18-1.4.1.1.3 18-1.4.1.1.3.2 18-1.4.1.1.3.2.r 19-1.4.3.2.1 20-1.4.3.2.2 21-1.4 21-1.4.2.1 22-1.4.2.1 23-1.4.2.1.2
SDL-AMR-09
bio-exp_0001.3
As shown in Fig. 5A , PLX4032 treatment increased HER3 and HER2 mRNAs in all six BRAF @-@ mutant thyroid cancer cell lines tested .
Ras
Nakashima
GDP
Ras
-
Axin
-
bio.ras_0001.7
SDL-AMR-09
Growth factors can turn on Ras by activating Guanine nucleotide Exchange Factors ( GEFs ) or by inhibiting the GTPase Activating Proteins ( GAPs ) or by both mechanisms .
0-1.1.1 1-1.1.1 2-1 3-1.1 4-1.1 5-1.1.2.1.1 6-1.1.3.r 7-1.1.3.1 8-1.1.3.1.2.1.1 9-1.1.3.1.2.1.2 10-1.1.3.1.2.1.3 11-1.1.3.1.2.1.4 15-1.1.3 17-1.1.3.2 19-1.1.3.2.2.1.1.1.1 20-1.1.3.1 20-1.1.3.2.2.1 21-1.1.3.2.2 25-1.1.3
U0126
SUM149
5
As shown in Fig. 4A , the FBm or S729A mutation had no effect on transformation induced by the V600E or G469A B @-@ Raf protein , both of which possess high kinase activity .
1-1.4 2-1.4.1.r 3-1.4.1 4-1.4.1.1 8-1.2 9-1.2.2.1 10-1.2.1 10-1.2.2 10-1.3.1.1.1 10-1.3.1.1.1.2 10-1.3.1.1.1.2.r 10-1.3.1.1.2 10-1.3.1.1.2.2 10-1.3.1.1.2.2.r 11-1.2.1.1.2 12-1.1 12-1.1.r 12-1.2.1.1.2.1 12-1.2.1.1.2.1.r 13-1 14-1.3.r 15-1.3 16-1.3.1 17-1.3.1.1.r 19-1.3.1.1.1.2.1 20-1.3.1.1 21-1.3.1.1.2.2.1 22-1.2.1.1.1.1 22-1.3.1.1.1.1.1 22-1.3.1.1.2.1.1 24-1.2.1.1.1.1 24-1.3.1.1.1.1.1 24-1.3.1.1.2.1.1 25-1.2.1.1.2.2 31-1.3.1.1.3.1 33-1.3.1.1.3
bio.mskcc_0001.31
SDL-AMR-09
Ras
PKI166
HER2
DNA
DNA
N terminus
-
urea
Venable
p90 ribosomal S6 kinase
HER3
1
BRAF
C-Raf
KRAS
clathrin
p38 SAPK
PI3KAKT
1.2
36
p38 SAPK
CKI
bio.chicago_2015.17089
SDL-AMR-09
The analogous result for PKC interaction with Par6 in the lower panel shows that , similarly to p62 , Par6b binds to PKC only when the PKC OPCA motif is not mutated and the back of Par6b has the wild @-@ type Lys 20 .
1-1.1.2 2-1.1 2-1.1.1 2-1.1.1.r 3-1.1.3.r 4-1.1.3.1.1.1 5-1.1.3 8-1.1.4.r 10-1.1.4.1 10-1.1.4.1.1 10-1.1.4.1.1.r 11-1.1.4 12-1 15-1.2.5 16-1.2.5.1.r 17-1.2.5.1.1.1 19-1.2.1 20-1.2 21-1.2.2.r 22-1.2.2 23-1.2.4 26-1.2.3.1.2.1.2 27-1.2.3.1.2.1.1.1 28-1.2.3.1.2 30-1.2.3.1.1 30-1.2.3.1.1.r 31-1.2.3.1 32-1.2.3 34-1.2.3.2.1 35-1.2.3.2.1.1.r 36-1.2.3.2.1.1 37-1.2.3.2 39-1.2.3.2.2.3 41-1.2.3.2.2.3 42-1.2.3.2.2.2.1 43-1.2.3.2.2.1
e
32
EGFR
30
B-Raf
Ozawa
PKI166
MEK
trypsin
HER3
ASPP2
5-fluorouracil
SDL-AMR-09
24885690
a_pmid_2488_5690.68
0-1.2 2-1.3 3-1.2.1.1 4-1.2.1 6-1.1.1 7-1.1.3 8-1.1 9-1.1.2 10-1.1.2.1.r 12-1.1.2.1.3 14-1.1.2.1.2 16-1.1.2.1 19-1.1.2.1.1.1.1.1 22-1.1.2.1.1.1 22-1.1.2.1.1.1.2 22-1.1.2.1.1.1.2.r 23-1.1.2.1.1.2.2.1 24-1.1.2.1.1.2.2.2 25-1.1.2.1.1 28-1.1.3.1.1 29-1.1.3.1.1 32-1.1.3.1.1.1.r 33-1.1.3.1.1.1 34-1.1.3.1.1.1.1 35-1.1.3.1.1.1.1.1.r 36-1.1.3.1.1.1.1.1.1.2 36-1.1.3.1.1.1.1.1.1.2.1 36-1.1.3.1.1.1.1.1.1.2.1.r 37-1.1.3.1.1.1.1.1.1.1 38-1.1.3.1.1.1.1.1.1 39-1.1.3.1.1.1.1.1 40-1.1.3.1.1.1.1.1.2.1 40-1.1.3.1.1.1.1.1.2.1.1 40-1.1.3.1.1.1.1.1.2.1.1.r 41-1.1.3.1.1.1.1.1.2 44-1.1.3.1.1.1.1.1.2.2 45-1.1.3.1 49-1.1.3.1.2 50-1.1.3.1.2.1.1 52-1.1.3.1.2.1.1 53-1.1.3.1.2.1 55-1.1.3.1.2.1.2 56-1.1.3.1.2.1.2.2.r 57-1.1.3.1.2.1.2.2.2 58-1.1.3.1.2.1.2.2 60-1.1.2.1.1.2.2.1 61-1.1.2.1.1.2.2.2 64-1.1.3.1.2.1.2.2.3.1.1.1
Complementing and extending previous studies , we thus provide evidence from an endogenous and quantitative genetic model of <i> BRAF </i>@ -@ mutant colorectal cancer cells , thereby ruling out the occurrence of artifacts caused by unspecific cellular response or incomplete knockdown in RNAi setups and , likewise , avoiding inter @-@ species bias potentially experienced in mouse models of colorectal cancer [ @<xref ref-type="bibr" rid="B30"> 30 </xref>@ ] .
t
SDL-AMR-09
10677502
0-1.1.1.2 1-1.1.1 1-1.1.1.3.1 2-1.1.1.1.r 3-1.1.1.1.1.1 4-1.1.1.3.r 5-1.1.1.3 6-1.1.1.3 7-1.1.1.3.1.1 9-1.1.4 10-1.1.3 10-1.1.3.r 11-1.1 12-1.1.2.2.1.1.1 14-1.1.2.2.1.1.1 16-1.1.2.2 17-1.1.2.1.1.1 18-1.1.2 19-1 20-1.2.3 21-1.2 22-1.2.2.2.1.1.1 24-1.2.2.2 25-1.2.2.1 26-1.2.2 27-1.2.4 28-1.2.4
High concentrations of stauro of up to 1 microM only partially inhibit IL @-@ 3 @-@ stimulated Bcl2 phosphorylation but completely block PKC @-@ mediated Bcl2 phosphorylation in vitro
bel_pmid_1067_7502.3614
0-1.1.1.2 1-1.1.1 2-1.1.1.1.r 3-1.1.1.1.1.1 4-1.1 5-1.1.2.3 6-1.1.2 8-1.1.1.1.1.1 8-1.2.2.1.1.1 9-1.1.2.2.r 11-1.1.2.2.1.1.1 12-1.1.2.2 15-1.1.2.2.2 16-1.1.2.2.2.1.r 17-1.1.2.2.2.1 18-1.1.2.2.2.1.1.r 19-1.1.2.2.2.1.1 23-1.1.3.1.1.1.1.1.1 24-1.1.3.1.1.1 25-1.1.3.1.1.1.2.1 27-1.1.3.1.1.2.1 29-1.1.3.1.2.1.1.1.1 30-1.1.3.1.2.1 31-1.1.3.1.2.1.2.1.1 33-1.1.3.1.2.2.1 35-1.1.3.1.3.1.1.1.1 36-1.1.3.1.3.1 37-1.1.3.1.3.1.2.1 39-1.1.3.1.3.2.1 42-1.2.1.1.1 44-1.2.1.1.1 45-1.2 47-1.2.2 50-1.2.2.2.r 51-1.2.2.2.1.1 53-1.1.2.2.2.1.2.1.1 56-1.2.2.2.2.2 57-1.2.2.2.2.2 58-1.2.2.2 58-1.2.2.2.2 58-1.2.2.2.2.r 59-1.2.2.2.2.1.r 61-1.2.2.2.2.1 62-1.2.2.2.2.1 64-1.2.3.1.1.1.1.1.1 65-1.2.3.1 65-1.2.3.1.1.1 65-1.2.3.1.3.1 65-1.2.3.1.4.1 66-1.2.3.1.1.1.2.1 66-1.2.3.1.3.1.2.1 66-1.2.3.1.4.1.2.1 68-1.2.3.1.2.2.1 70-1.2.3.1.2.1.1.1.1 71-1.2.3.1.2.1 72-1.2.3.1.2.1.2.1 74-1.2.3.1.2.2.1 76-1.2.3.1.3.1.1.1.1 77-1.2.3.1.3.1 78-1.2.3.1.3.1.2.1 80-1.2.3.1.3.2.1 82-1.2.3.1.4.1.1.1.1 83-1.1.3.1 83-1.2.3.1 83-1.2.3.1.1.1 83-1.2.3.1.3.1 83-1.2.3.1.4.1 84-1.2.3.1.1.1.2.1 84-1.2.3.1.3.1.2.1 84-1.2.3.1.4.1.2.1 86-1.2.3.1.3.2.1
bio.chicago_2015.19139
These functions of cadherin require intracellular attachment of cadherin to the actin cytoskeleton that is dependent on binding of cadherin to catenins ( Hirano et al. , 1987 ; Nagafuchi and Takeichi , 1988 ; Ozawa et al. , 1990 ) ; beta @-@ catenin mediates the linkage of cadherins to alpha @-@ catenin , which in turn interacts with the actin cytoskeleton ( Aberle et al. , 1994 ; Hulsken et al. , 1994 ; Jou et al. , 1995 ; Rimm et al. , 1995 ) .
SDL-AMR-09
LIF
EGFR
2-1.3.2 2-1.3.2.1 2-1.3.2.1.r 3-1.3.1 4-1.3 7-1.1.1.1 8-1.1.1 11-1.1.1.2.2.1.1 13-1.1.1.2 14-1.1.1.2.1 16-1.1 17-1 18-1.2 20-1.4.1.1.1 21-1.4.1.1 21-1.5.1.2.1 22-1.4.1 23-1.4 25-1.5 27-1.5.1 27-1.5.1.2.1.1.2.1 28-1.5.1.3 29-1.5.1.1.1 31-1.5.1.2.1.1.2.1.1.1 33-1.5.1.2.1.1.2 35-1.5.1.2.1.1.1.1 38-1.5.1.2.1.1.3.1.1
SDL-AMR-09
24885690
a_pmid_2488_5690.40
In the first targeting round , an oncogenic allele of <i> BRAF </i> exon 15 was recombined and deleted by somatic cell gene targeting to generate the cell clone RBOW ( RKO @-@ derived <i> BRAF </i>@ <sup> onc/wt/- </sup> ) .
ATP
MEK
BRAF
serine
621
SDL-AMR-09
pmid_1528_0923.84
1-1.3 3-1.1 4-1.1.1 5-1.1.1.1.1 6-1.1.1.1 7-1.1.1.1.2.r 8-1.1.1.1.2.1.1.1 9-1.1.1.1.2 10-1.1.1.1.2.2.1.1 12-1.1.2.1.1.1.1 14-1.1.2.1.2.1.1 16-1.1.2.1.2.1.1 18-1.1.2.1.2.1.1 19-1 20-1.2.2 21-1.2.1 22-1.2
As expected , cells expressing low levels of EGFR and HER2 , GI101A , MDA @-@ MB @-@ 435 showed least growth inhibition .
15280923
-
bio.chicago_2015.18396
Axin enhances the phosphorylation of beta @-@ catenin by GSK @-@ 3 beta by positioning GSK @-@ 3 beta close to beta @-@ catenin , resulting in the inhibition of the Wnt signaling pathway ( 32 ) .
0-1.1.1.1 1-1 3-1.2 4-1.2.1.r 5-1.2.1.1.1 7-1.2.1.1.1 8-1.2.2.r 9-1.2.2.1.1 12-1.2.1.1.1 13-1.3.r 14-1.3 15-1.3.2 18-1.3.3.2 19-1.3.3 21-1.3.3.2 22-1.3.3.2 23-1.3.3.2 25-1.4 26-1.4.1.r 28-1.4.1 29-1.4.1.1.r 31-1.4.1.1.1.1 32-1.4.1.1.2 33-1.4.1.1 35-1.4.2.1.1.1
SDL-AMR-09
GTPase
SDL-AMR-09
bio.ras_0001.2
Importantly the signaling enzymes encoded by PIK3CA and BRAF are , in part , regulated by direct binding to activated forms of the Ras proteins suggesting that dysregulation of this key step in signaling is critical for tumor formation .
0-1.4 2-1.2.1 3-1.2 4-1.2.2 5-1.2.2.1.r 6-1.2.2.1.1.1.1 7-1.2.2.1 8-1.2.2.1.2.1.1 11-1.3.r 12-1.3 12-1.3.r 14-1 16-1.1.3 17-1.1 18-1.1.2.r 19-1.1.2.2 20-1.5.1.2 23-1.1.2.1.1 25-1.5 27-1 33-1.2.1 35-1.5.1 37-1.5.1.2.1 38-1.5.1.2
-
-
IGF-IR
E1A-RG2
BRAF
alanine
ASPP1
SKBR3
Mek
G466A
HER2
bio.bmtr_0005.21
0-1.3 1-1.3.1 6-1 6-1.1 6-1.1.r 7-1.2.1.r 8-1.2.1.1.1.1.1 9-1.2.1 10-1.2.1.1 11-1.2.1.1.2.1.1 13-1.2.1.1.3 14-1.2.1.1.3.1.1.1.1 15-1.2.1.1.3.1
Until now , it has been unclear how RAS could affect ASPP2 to enhance p53 function .
SDL-AMR-09
K46^mA
MEK
117
lysine
Ras
Ras
DP
Cooper
Struhl
e2
a4
BRAF
Yu
5.0
breast cancer
Breast_cancer
0-1.1 1-1 2-1.2.2 3-1.2 3-1.2.1 3-1.2.1.r 4-1.2.1.1.r 5-1.2.1.1.1.1.1 7-1.2.1.1.1.1.1 8-1.2.1.1 9-1.2.1.1.2 10-1.2.1.1.2.1.2 10-1.2.1.1.2.1.3.1.2 12-1.2.1.1.2.1.2 12-1.2.1.1.2.1.3.1.2 13-1.2.1.1.2.1.1.1 16-1.2.1.1.2.1.3.r 17-1.2.1.1.2.1.3.1.2 19-1.2.1.1.2.1.3.1.2 20-1.2.1.1.2.1.3 21-1.2.1.1.2.1.3.2.2.1 22-1.2.1.1.2.1.3.2 22-1.2.1.1.2.1.3.2.2 22-1.2.1.1.2.1.3.2.2.r 23-1.2.1.1.2.1.3.1.1.1 23-1.2.1.1.2.1.3.2.1.1 25-1.3.1 26-1.3.1.1
bio.bmtr_0002.13
We observed analogous results in CHO @-@ KI cells expressing wild @-@ type ERBB3 in combination with wild @-@ type or T677A mutant HER2 ( Figure 6B ) .
SDL-AMR-09
CD72
7
IL-6
GSK-3beta
PI3-Kinase
p3
746
We utilized an unbiased mass spectrometry - based approach to identify ubiquitination sites of Ras .
0-1.1 1-1 3-1.2.1 3-1.2.1.1 3-1.2.1.1.r 4-1.2.2.1.1 5-1.2.2.1 7-1.2.2 8-1.2 10-1.3 11-1.3.2.2 12-1.3.2 13-1.3.2.1.r 14-1.3.2.1.1.1
bio.ras_0003.1
SDL-AMR-09
2B
interrogative
ASPP2
Site @-@ Specific Monoubiquitination Activates Ras by Impeding GTPase Activating Protein ( PMC3537887 )
bio.bmtr_0004.1
0-1.2.1.2.1 2-1.2.1.2 3-1.2.1 3-1.2.1.1 3-1.2.1.1.r 4-1.2 5-1.2.2.1.1 6-1.2.3.r 7-1.2.3 8-1.2.3.2.1.1 9-1.2.3.2.1.2 10-1.2.3.2.1.3 12-1.1
SDL-AMR-09
K-Ras
Pin1
PUMA was found to be highly abundant specifically in serum starved RBW @-@ 1 ( Figure <xref ref-type="fig" rid="F2"> 2 </xref>@ H ) .
0-1.3.1.1 1-1.3.r 2-1.4 4-1.3.r 5-1.2 6-1 7-1.6 8-1.1.r 9-1.1.2.1 10-1.1.2 11-1.1.1.1 13-1.1.1.1 15-1.5.1
24885690
a_pmid_2488_5690.63
SDL-AMR-09
B-Raf
bmtr_0007.10
0-1 0-1.2.1 0-1.2.1.2.1.1 2-1.1.4.r 3-1.1.4.3 4-1.1.4.2 5-1.1.4.4.1.2 7-1.1.4.4.1.1.1 8-1.1.4 10-1.1.4.1.1 12-1.1.1.1.1.1 12-1.1.4.4.1.1.1 13-1.1.1 13-1.1.4.4.1.2 15-1.1.2 16-1.1 17-1.1.3.r 19-1.1.3.4 20-1.1.3.5.2.1 21-1.1.3.5.2.2 22-1.1.3 22-1.1.3.3.1 23-1.1.3 24-1.1.3.1.1 25-1.1.3.1.2 27-1.1.3.3.1.1.1 28-1.1.3 28-1.1.3.3.1 32-1.1.3.2.2.1.1.1 33-1.1.3.2.2 35-1.1.3.2 38-1.1.3.2.1 39-1.1.3.2.1.1.r 40-1.1.3.2.1.1.1.1 42-1.1.3.2.1.1.1.1 44-1.1.3.2.1.1.1.1 52-1.2.1.1 53-1.2.1.1.1
SDL-AMR-09
Moreover , with another different phospho @-@ ASPP2 antibody , ES1 , ASPP2 phosphorylation was also observed in a human colon cancer cell line HKe3 ER : HRASV12 cells , in which RAS activation is induced upon the addition of 4 @-@ hydroxytamoxifen ( 4 @-@ OHT ) [ 2,10,11 ] ( Figure 1E ) .
PMC3847091
ERK-2
10648414
bel_pmid_1064_8414.21218
B9 clones expressing either wild @-@ type FGFR3 at high levels or mutant FGFR3 displayed increased phosphorylation of STAT3 and higher levels of bcl @-@ x( L ) expression than did parental B9 cells after cytokine withdrawal .
0-1.1.1 1-1.1 2-1.1.2 4-1.1.2.1.1.2 6-1.1.2.1.1.2 7-1.1.2.1.1.1.1 7-1.1.2.1.2.1.1 9-1.1.2.1.1.3.1 10-1.1.2.1.1.3 11-1.1.2.1 12-1.1.2.1.2 12-1.1.2.1.2.2 12-1.1.2.1.2.2.r 13-1.1.2.1.1.1.1 13-1.1.2.1.2.1.1 14-1 15-1.2.1.2 16-1.2.1 17-1.2.1.1.r 18-1.2.1.1.1.1 19-1.2 20-1.2.2.1 20-1.2.2.1.1 20-1.2.2.1.1.r 21-1.2.2 22-1.2.2.2.r 23-1.2.2.2.1.1.1 28-1.2.2.2 29-1.2.3.r 31-1.2.3.2 32-1.2.3.1.1 33-1.2.3 34-1.2.3.3 35-1.2.3.3.1.1.1.1 36-1.2.3.3.1
SDL-AMR-09
ASPP1
-
c2
Ras
MAPK1
10
0-1 1-1.1 3-1.1
Passage 1 @-@ 2 ( Discussion/Conclusion )
SDL-AMR-09
bio.bmtr_0005.18
ERK12
Ksr1
MAPK
6C
ERK12
1-1.2.2 2-1.2 3-1.2.1.r 4-1.2.1 6-1.3 8-1 9-1.1.r 11-1.1.1.1 12-1.1 16-1.1.2 22-1.1.2.1.r 22-1.3.r 24-1.1.2.1.1.1 25-1.1.2.1 26-1.1.2.1.2.r 28-1.1.2.1.2 29-1.1.2.1.2.1.r 30-1.1.2.1.2.1.1 31-1.1.2.1.2.1 32-1.1.2.1.2.1.2.r 34-1.1.2.1.2.1.2.2.2.1.1 35-1.1.2.1.2.1.2.2.1.1 37-1.1.2.1.2.1.2.2.1.1 38-1.1.2.1.2.1.2.1 39-1.1.2.1.2.1.2
bio-kappa_0001.3
SDL-AMR-09
The molecular basis for this has recently been elucidated by the Shaw lab , who has shown that the ability of acting as an activator depends on the presence of negative charges in the Raf N @-@ terminal acidic motif .
PP2A
Ras
Finelli
SDL-AMR-09
PSPs dephosphorylate phosphoserine and phosphothreonine residues .
bio-kappa_0001.9
1-1 3-1.1 5-1.1.1 5-1.1.2
B-Raf
actin
proline
52
phosphopeptide
MDA-MB-435
B-Raf
PKCe
Mek
CRB
senescence-associated β-galactosidase
p
3
S3
1
G466A
-
8505C
H-Ras
8505C
Sasaki et al. , “ Ubiquitination of Ras enhances activation and facilitates binding to select downstream effectors ” ( PMC3437993 )
SDL-AMR-09
0-1.2.1.1.1 1-1.2 2-1.2.2.1 5-1.3.1.1 6-1.3.1.1.1.r 7-1.3.1.1.1.1.1 8-1.3.1 9-1.3.1.2 10-1.3 11-1.3.2 12-1.3.2.2 13-1.3.2.2.1.r 14-1.3.2.2.1.2 15-1.3.2.2.1.1 16-1.3.2.2.1 19-1.1
bio.bmtr_0001.1
GDP
2
n4
IL-6
B-Raf
PKI166
23
24
111
p4
ASPP2
AZD6244
CM
For B @-@ Raf , previous work by Brummer et al. ( 3 ) identified the C @-@ terminal S750 and T753 residues as sites phosphorylated by activated ERK .
1-1.2.1.2.2.1.1 3-1.2.1.2.2.1.1 5-1.1.1.2 6-1.1 6-1.1.1 6-1.1.1.r 7-1.1.1.1.r 8-1.1.1.1.1.1.1 9-1.1.1.1 10-1.1.1.1.2.1 12-1.1.2.1 14-1 16-1.2.1.2.1.1 18-1.2.1.2.1.1 20-1.2 22-1.2.1 22-1.2.2 23-1.1.1.2.r 23-1.3.r 24-1.3.1 25-1.3 26-1.3.2.r 27-1.3.2.2 28-1.3.2.1.1
SDL-AMR-09
bio.mskcc_0001.49
5
ATM
In contrast , the S729A mutation reduced the transforming activities of the oncogenic proteins with intermediate or impaired kinase activity , causing a reduction in focus number and a flatter cell morphology ( Fig . 4A ) .
1-1 4-1.1.1.1 5-1.1.1 6-1.1 8-1.1.2.3 9-1.1.2.1 12-1.1.2.1.1.1 12-1.1.2.1.1.1.1.2.1 13-1.1.2.1.1 13-1.1.2.2.1 15-1.1.2.1.3 16-1.1.2 17-1.1.2.2.3 18-1.1.2.1.2 19-1.1.2.1 19-1.1.2.2 21-1.1.3 23-1.1.3.1.1 24-1.1.3.1.1.1.r 25-1.1.3.1.1.1.1 26-1.1.3.1.1.1 27-1.1.3.1 29-1.1.3.1.2.2 29-1.1.3.1.2.2.1 29-1.1.3.1.2.2.1.r 30-1.1.3.1.2.1 31-1.1.3.1.2 33-1.1.4.1 35-1.1.4.1.1
bio.mskcc_0001.34
SDL-AMR-09
3-1 4-1.2.r 5-1.2.1.1.1.1 7-1.2.1.1.1.1 9-1.2.1.1.2.1 12-1.2.1 14-1.2.1.2 15-1.2.1.2.2 20-1.2.1.2.2.1.1.1.1 21-1.2.1.2.2.1 22-1.2.1.2.2.2.1 24-1.2.1.2.2.2.2.1 25-1.2.1.2.2.2.2 26-1.2.1.2.2.2.2 27-1.2 28-1.2.2 29-1.2.2.2 31-1.2.2.2.1 32-1.2.2.2.1.1 35-1.1.1.1.1 39-1.1.1.1.2
a_pmid_2488_5690.34
24885690
SDL-AMR-09
It has been shown that B @-@ Raf @<sup> V600E </sup> is sufficient to promote proliferation via Erk 1 @/@ 2 signaling independently of exogenous growth factors and confers mechanisms to evade apoptosis [ @<xref ref-type="bibr" rid="B14"> 14 </xref>@ - @<xref ref-type="bibr" rid="B16"> 16 </xref>@ ] .
Bcl2
10744722
bel_pmid_1074_4722.15498
1-1.3 2-1.3.1.r 3-1.3.1 4-1.3.1.1 6-1.1.1.1.1 6-1.1.3.1.1 7-1.1.1.2 7-1.1.3.2 9-1.1.1.2.1.1 9-1.1.3.2.1.1 9-1.1.3.2.1.1.1 9-1.1.3.2.1.1.1.r 10-1.1.1.2.1 10-1.1.3.2.1 12-1.1.2 13-1.1 14-1.1.3.r 17-1.1.1.2.1.1 17-1.1.3.2.1.1 17-1.1.3.2.1.1.1 17-1.1.3.2.1.1.1.r 18-1.1.1.2.1 20-1.2.2 23-1.2.2.1.2 24-1.2.2 26-1.2.2.1.1.1.1 27-1.2.2.1 27-1.2.2.2 29-1.2 30-1.2.1.r 31-1.2.1 36-1.2.1.1.2 37-1.2.1.1.2.1.1
SDL-AMR-09
As shown in Fig. 6A , ATM immunoprecipitated from irradiated cells was more active than that from unirradiated cells , and both the basal and radiationinduced ATM activities were inhibited by caffeine with an IC50 at around 200 M.
147
lysine
interrogative
Phosphorylation of ASPP2 by RAS @/@ MAPK Pathway Is Critical for Its Full Pro @-@ Apoptotic Function ( PMC3847091 )
0-1.2.1 1-1.2.1.1.r 2-1.2.1.1.1.1 3-1.2.1.2.r 4-1.2.1.2.1.1 6-1.2.1.2.1.1 7-1.2.1.2 9-1.2 10-1.2.2.r 11-1.2.2.1 11-1.2.2.1.r 12-1.2.2.3 13-1.2.2.2.1 15-1.2.2.2 16-1.2.2 18-1.1
SDL-AMR-09
bio.bmtr_0005.1
bio.chicago_2015.18599
Moreover ectopic expression of cyclin E does not activate E2F in the absence of cdk4 and cdk6 activity ( Lukas et al. , 1997 ) .
0-1 0-1.2.1.1 1-1.1.2.2 2-1.1.2 3-1.1.2.1.r 4-1.1.2.1.1.1 5-1.1.2.1.1.2 7-1.1.1 7-1.1.1.r 8-1.1 9-1.1.3.1.1 10-1.1.4.r 12-1.1.4 13-1.1.4.1.r 14-1.1.4.1.1.1.1.1 15-1.1.4.1.1 16-1.1.4.1.1.2.1.1 17-1.1.4.1 19-1.2.1.1.1.1.1 20-1.2.1.1 21-1.2.1.1.2.1 23-1.2.1.2.1
SDL-AMR-09
p4
N-terminus
s2
bio.bmtr_0001.3
2-1.1.1.1.2 2-1.1.1.2.3 3-1.1.1.1.1.1 5-1.1.1.2.3.1.1.1 7-1.1.1.2.3 8-1.1.1.2.1.1 8-1.1.1.2.2.1 10-1.1.1.2.1.1 12-1.1.1.2.1.1 12-1.1.1.2.2.1 14-1.1.1.2.2.1 18-1.1 18-1.1.3.1.1.1 19-1.1.2.r 20-1.1.2.1.1 21-1.1.2 22-1.1.3.r 23-1.1.3 23-1.1.3.1.1 24-1.1.3.1 25-1.1.3.1.1.1.1.r 26-1.1.3.1.1.1.1.2 27-1.1.1.2.1.1 27-1.1.1.2.2.1 27-1.1.3.1.1.1.1.1.1 29-1.1.1.2.2.1 29-1.1.3.1.1.1.1.1.1 31-1.1.4.1 33-1.1.4.1.1 35-1 36-1.2 37-1.2.2.r 38-1.2.2.2 39-1.2.2.1 40-1.2.2
His @-@ tagged ubiquitin and Flag @-@ tagged K @-@ Ras4B ( K @-@ Ras hereafter ) were expressed in HEK293T cells at levels similar to endogenous K @-@ Ras ( Fig . 1B ) and subjected to sequential affinity chromatography .
SDL-AMR-09
1-2
HCC827
B-Raf
PP5
-
Ras
t
h3
B-Raf
32
The apparent counterselection against inactivation of B Raf @<sup> V600E </sup> might indicate the presence of an oncogene addiction for B @-@ Raf @<sup> V600E </sup> as a cancer cell trait in RKO [ @<xref ref-type="bibr" rid="B19"> 19 </xref>@ ] .
1-1.1.1.1 3-1.1.1.2 4-1.1.1.2.1 4-1.1.1.2.1.1 4-1.1.1.2.1.1.r 5-1.1.1.2.1.2.r 6-1.1.1.2.1.2.1.1 7-1.1.1.2.1.2.1.1 9-1.1.1.2.1.2.2.1 11-1 12-1.1 15-1.1.2.r 17-1.1.2.1.2 18-1.1.2.1 19-1.1.2.1.1.r 20-1.1.2.1.1 21-1.1.2.1.1 22-1.1.2.1.1 23-1.1.2.1.1 24-1.1.2.1.1 28-1.1.2.2.1.2.1 29-1.1.2.2 30-1.1.2 31-1.1.2.3.r 32-1.1.2.3.1.1 35-1.2.1.1.1
a_pmid_2488_5690.43
24885690
SDL-AMR-09
To test this hypothesis , we transiently transfected CHO @-@ KI cells , which do not express ERBB receptors endogenously , with wild @-@ type ERBB3 with either wild @-@ type EGFR or EGFR T669A .
1-1.5 2-1.5.2.2 3-1.5.2 3-1.5.2.1 3-1.5.2.1.r 5-1.1 6-1.4 7-1 8-1.2.1.1.1 10-1.2.1.1.1 11-1.2 15-1.2.2.1 15-1.2.2.1.r 16-1.2.2 17-1.2.2.2.1.1 18-1.2.2.2 19-1.2.2.3 22-1.3.1.2 22-1.3.2.1.2 24-1.3.1.2 24-1.3.2.1.2 25-1.3.1.1.1 28-1.3.1.2 28-1.3.2.1.2 30-1.3.1.2 30-1.3.2.1.2 31-1.3.2.1.1.1 31-1.3.2.2.1.1 32-1.3.2 33-1.3.2.1.1.1 33-1.3.2.2.1.1 34-1.3.2.2.2.1
bio.bmtr_0002.9
SDL-AMR-09
SDL-AMR-09
Through mutational analysis , we find that feedback phosphorylation disrupts the abilities of B @-@ Raf to bind activated Ras and to heterodimerize with C @-@ Raf .
1-1.3.2 2-1.3 4-1.1 5-1 6-1.2.r 7-1.2.1.1 8-1.2.1 9-1.2 11-1.2.2 12-1.2.2.1.r 13-1.2.2.1.1.1 15-1.2.2.1.1.1 16-1.2.2.2.r 17-1.2.2.2.1 18-1.2.2.2.1.2.2 19-1.2.2.2.1.2.1.1 20-1.2.2.2 22-1.2.2.2.2 23-1.2.2.2.2.2.r 24-1.2.2.2.2.2.1.1 26-1.2.2.1.1.1 26-1.2.2.2.2.2.1.1
bio.mskcc_0001.53
729
serine
Ras
VSMC
carcinoma
SDL-AMR-09
1-1.3 3-1.3.2 3-1.3.2.1 3-1.3.2.1.r 4-1.3.2.1.1.r 6-1.3.2.1.1.1 7-1.3.2.1.1.2 8-1.3.2.1.1 9-1.3.2.1.1.2.r 9-1.3.2.1.2.r 11-1.3.2.1.2.3 12-1.3.2.1.2 13-1.3.2.1.2.1.r 14-1.3.2.1.2.1 15-1.3.2.1.2.1 17-1.2.1.1.1 17-1.2.1.2.1.1.2.1.1.1 17-1.3.2.1.2.2.1.1.1 19-1.2.1.1.1 19-1.2.1.2.1.1.2.1.1.1 19-1.3.2.1.2.2.1.1.1 20-1.3.2.1.2.2 22-1.1 23-1 25-1.2 26-1.2.1.r 27-1.2.1 27-1.2.1.2 27-1.2.1.2.1.1.2.2 27-1.2.1.2.1.1.2.2.2 27-1.2.1.2.1.1.2.2.2.r 27-1.2.1.2.r 30-1.2.1.2.1.1.1.2.2 31-1.2.1.2.1.1.1.2.1 32-1.2.1.2.1.1.1.2 33-1.2.1.2.1.1.1 35-1.2.1.2.1.1 36-1.3.2.1.1.2.r 38-1.2.1.2.1.1.2.1.2 39-1.2.1.2.1.1.2.1.1.1 39-1.2.1.2.1.1.2.2.1.1 41-1.2.1.2.1.1.2.1.1.1 41-1.2.1.2.1.1.2.2.1.1 42-1.2.1.2.1.1.2 44-1.2.1.2.1.1.2.2.3.1 46-1.2.1.2.1.1.2.2.3 47-1.2.1.2.1.1.2.2.2.1 48-1.2.1.2.1.1.2.2.1.1 50-1.2.1.2.1.1.2.2.1.1 51-1.2.1.2.1.1.1
bio.mskcc_0001.38
To investigate the contributions of the various feedback sites to the overall effect of feedback phosphorylation on B @-@ Raf function , we generated a panel of mutants in which specific feedback phosphorylation sites were incorporated into either WT B @-@ Raf or the intermediate @-@ activity G466A B @-@ Raf protein .
-
tyrosine
CD72
Ras
MEK1
MAP2K1
15280923
1-1.1.1.1 1-1.1.1.1.1 1-1.1.1.1.1.r 2-1.1.1 3-1.1 4-1.1.2.1.2.1 5-1.1.2 6-1.1.2.2.2.1 7-1.1.2.2.2 8-1.1.2.1.1 8-1.1.2.2.1 9-1.1.2.1 9-1.1.2.2 11-1.1.2.1.1.1.1.1 12-1.1.2 13-1.1.2.2.1.1.1.1 15-1.1.2.2.1.1.1.1 17-1.1.2.2.1.1.1.1 18-1.1.2.1.1.1 18-1.1.2.2.1.1 20-1.1.3 22-1 24-1.2.3 25-1.2 27-1.2.4.1.1.1 28-1.1.2.1.2 28-1.2.4.1.1 29-1.2.4.1 31-1.2.2.r 33-1.2.2 34-1.2.2.1.r 35-1.2.2.1.1.1 37-1.2.2.1.1.1 39-1.2.2.1.1.1 40-1.2.2.1
The lower dose produced 46 and 21 % growth inhibition of SUM149 and MDA @-@ MB @-@ 468 cells , respectively , but had little effect ( 3.3 % inhibition ) on the growth of MDA @-@ MB @-@ 231 cells .
pmid_1528_0923.86
SDL-AMR-09
2C
154
PR
EGFR
-
threonine
68
37
76
cysteine
E2F
DNA
DNA
−−
actin
Cancer
cancer
tyrosine
C-Raf
SDL-AMR-09
Binding of filamin to actin bundles was determined in the absence of another ABP ( curve 1 , A , B ) or in the presence of saturating quantities of calponin ( curve 2 , A ) or - actinin ( curve 2 , B ) .
bio.chicago_2015.18974
0-1.1 1-1.1.1.r 2-1.1.1.1.1 3-1.1.2.r 4-1.1.2.1.1.1 5-1.1.2 7-1 8-1.2.r 10-1.2.1 11-1.2.1.1.r 12-1.2.1.1.2 13-1.2.1.1.1.1 15-1.2.1.2.1.3.1 16-1.2.1.2.1.3.1.1 18-1.2.1.2.1.1.1 20-1.2.1.2.1.2.1 22-1.2 25-1.2.2 26-1.2.2.1.r 27-1.2.2.1.1 28-1.2.2.1 29-1.2.2.1.1.1.r 30-1.2.2.1.1.1.1.1.1 32-1.2.2.1.1.1.1.2.1.2.1 33-1.2.2.1.1.1.1.2.1.2.1.1 35-1.2.2.1.1.1.1.2.1.1 37-1.2.2.1.1.1 39-1.2.2.1.1.1.2.1.1 41-1.2.2.1.1.1.1.2.1.2.1 42-1.2.2.1.1.1.1.2.1.2.1.1 44-1.2.1.2.1.2.1 44-1.2.2.1.1.1.2.2.1.1
-
-
S729A
6
Therefore , to further investigate both the impact of feedback phosphorylation and the contribution of heterodimerization to oncogenic B @-@ Raf function , we examined the transformation potential of oncogenic B @-@ Raf proteins containing mutations in either the feedback phosphorylation sites ( which exhibit increased heterodimerization ) or the S729 14 @-@ 3 @-@ 3 binding site ( which are unable to heterodimerize ) .
bio.mskcc_0001.28
0-1 2-1.1.2.1.1 2-1.1.2.1.1.2 2-1.1.2.1.1.2.r 3-1.1.3.3 4-1.1.3 7-1.1.3.2.1 8-1.1.3.2.1.1.r 9-1.1.3.2.1.1.1 10-1.1.3.2.1.1 11-1.1.3.2 13-1.1.3.2.2 14-1.1.3.2.2.1.r 15-1.1.3.2.2.1 16-1.1.3.2.2.2.1 17-1.1.3.2.2.2.1 18-1.1.3.2.2.2.1 19-1.1.3.2.2.2.1 20-1.1.3.2.2.2.1 21-1.1.3.2.2.2 23-1.1.1 24-1.1 26-1.1.2.1 29-1.1.2.1.1 29-1.1.2.1.1.2 29-1.1.2.1.1.2.1.2.1 29-1.1.2.1.1.2.r 30-1.1.2.1.1.1.1 32-1.1.2.1.1.1.1 33-1.1.2.1.1.3.1.1 35-1.1.2.1.1.3 39-1.1.2.1.1.3.1.1.1.1 40-1.1.2.1.1.3.1.1.1 41-1.1.2.1.1.3.1.1 44-1.1.2.1.1.3.1.1.2 45-1.1.2.1.1.3.1.1.2.1.1 46-1.1.2.1.1.3.1.1.2.1 48-1.1.2.1.1.3.1 51-1.1.2.1.1.3.1.2.3.1.1.1 53-1.1.2.1.1.3.1.2.3.1.1.1 55-1.1.2.1.1.3.1.2.3.1.1.1 56-1.1.2.1.1.3.1.2.3 57-1.1.2.1.1.3.1.1 61-1.1.2 61-1.1.2.1.1.3.1.2.4.1 61-1.1.2.1.1.3.1.2.4.1.1 61-1.1.2.1.1.3.1.2.4.1.1.r 63-1.1.2.1.1.3.1.2 63-1.1.2.1.1.3.1.2.4 63-1.1.2.1.1.3.1.2.4.r
SDL-AMR-09
ERK12
However , these results are primarily based on non @-@ quantitative RNA interference ( RNAi ) methods which are prone to artifacts in mammalian cells due to nonspecific defense mechanisms [ @<xref ref-type="bibr" rid="B17"> 17 </xref>@ ] .
SDL-AMR-09
24885690
a_pmid_2488_5690.35
0-1 2-1.1.1.2 3-1.1.1 3-1.1.1.1 3-1.1.1.1.r 5-1.1.3 5-1.1.3.r 6-1.1 7-1.1.2.r 8-1.1.2.2.1 8-1.1.2.2.1.r 10-1.1.2.2 11-1.1.2.3.1.1.1 12-1.1.2.3 16-1.1.2 19-1.1.2.1 20-1.1.2.1.1.r 20-1.1.2.1.3 21-1.1.2.1.1 22-1.1.2.1.2.r 23-1.1.2.1.2.1.1.1 24-1.1.2.1.2 25-1.1.2.1.3 26-1.1.2.1.3 27-1.1.2.1.3.1.2 27-1.1.2.1.3.1.2.1 27-1.1.2.1.3.1.2.1.r 28-1.1.2.1.3.1.1 29-1.1.2.1.3.1 32-1.2.1.1.1
Activated Ras controls diverse signaling pathways that ultimately determine Ras - induced cellular responses such as cell proliferation , survival , differentiation and motility .
0-1.1.2 1-1.1.1.1 2-1 3-1.2.1 4-1.2.2 5-1.2 7-1.2.3.2 8-1.2.3 9-1.2.3.1.3.1 11-1.2.3.1.3 12-1.2.3.1.1 13-1.2.3.1 15-1.2.3.1.2.r 15-1.2.3.2.r 16-1.2.3.1.2.1.1 17-1.2.3.1.2.1 19-1.2.3.1.2.2 21-1.2.3.1.2.3 22-1.2.3.1.2 23-1.2.3.1.2.4
bio.ras_0002.1
SDL-AMR-09
MAPK1
Cancer
cancer
Ras17N
e
B
DNA
DNA
EGFR
e
0-1.1.1.1.1.1 2-1.1.1.1.1.1 4-1.1.1.1.1.1 5-1.1.1 6-1.1 6-1.2 8-1.1.2.1 8-1.2.2.1 9-1.1.2 9-1.2.2 10-1.1.2.2 10-1.2.2.2 14-1.1.2.2.1.1.1 16-1 17-1.2.2.2.1.1.1 19-1.1.2.2.1.1.1 19-1.2.2.2.1.1.1 21-1 22-1.3 27-1.4.1.1.1
SDL-AMR-09
14 @-@ 3 @-@ 3 dimers bind to phosphorylation sites present in both the N @- and C @-@ terminal regions and stabilize the autoinhibited state ( 22 ) .
bio.mskcc_0001.2
PLX4032
RAS
Ras
threonine
0-1.1.2 3-1.1.1.1.1 4-1.1 6-1 7-1.2.r 8-1.2.1.1 10-1.2.1.1 12-1.2.1.1 13-1.2 16-1.2.2 17-1.2.2.1.2.1 18-1.2.2.1.2 19-1.2.2.1.1.1 21-1.2.2.2.r 22-1.2.2.2 23-1.2.2.2.1.r 25-1.2.2.2.1.1.1 26-1.2.2.2.1 28-1.1.2 29-1.2.2.2.1.2.1.1 30-1.2.2.2.1.2.1 31-1.2.2.2.1.2 32-1.2.2.2.1.2.2.2 33-1.2.2.2.1.2.2.1.1.1 35-1.2.2.2.1.2.2.1.1.1 36-1.2.2.2.1.2.2
SDL-AMR-09
15280923
High pERK1 @/@ 2 levels were detected in MDA @-@ MB @-@ 435 cells , which have very little EGFR , in contrast to the SUM149 cells with high EGFR expression and low ERK1 @/@ 2 activity .
pmid_1528_0923.77
beta-catenin
RASMAPK
0-1.1.1 3-1.1.2.1.1.4 5-1.1.2.1.1.1 6-1.1.2.1.1.2 9-1.1.2.1.1.4 11-1.2.1 14-1.2.2.1.1.1 16-1.3.1 18-1.3.2.1.1.1 19-1.3.2.1.1.2 21-1.4.1 23-1.4.2.1.3.1.1 24-1.4.2.1.3.r 25-1.4.2.1.2 26-1.4.2.1.1.1.1 27-1.4.2.1.1.r 28-1.4.2.1 30-1.5.1 32-1.5.2.1.1 33-1.5.2.1.1.1 34-1.5.2.1 36-1.6.1 38-1.6.2.1.1 39-1.6.2.1 41-1.7.1 43-1.7.2.1.1.1 45-1.7.2.1.1 46-1.7.2.1 48-1.8.1 50-1.8.2.1.1.1 51-1.8.2.1.1.2 53-1.9.1 55-1.9.2.1.1.1 56-1.9.2.1.1.2 58-1.10.1 60-1.10.2.1.1.1 62-1.10.2.1.1.1 63-1.10.2.1.1.2 64-1.10.2.1.1.3 66-1.11.1 68-1.11.2.1.1.1 69-1.11.2.1.1.2 70-1.11.2.1.1.3 72-1.12.1 74-1.12.2.1.2 75-1.12.2.1.1.1 77-1.13.1 79-1.13.2.1 81-1.14.1 83-1.14.2.1.1.1 88-1.15.2.1.1.1 89-1.15.2.1.1.2 90-1.15.2.1.1.3 91-1.15.2.1.1.4 92-1.15.2.1.1.5 93-1.15.2.1.1.6 95-1.16.1 97-1.16.2.1.1.1 98-1.16.2.1.1.2 99-1.16.2.1.1.3 101-1.17.1 103-1.17.2.1.1.2 104-1.17.2.1.2 108-1.18.1 110-1.18.2.1.1.1 111-1.18.2.1.1.2 112-1.18.2.1.1.3 113-1.18.2.1.1.4 115-1.19.1 117-1.19.2.1 117-1.19.2.1.1 117-1.19.2.1.1.r 118-1.19.2.1.1.1.r 119-1.19.2.1.1.1.1.1.1 121-1.19.2.1.1.1.1.1.1 122-1.19.2.1.1.1 123-1.19.2.1.1.1.2.1.1 125-1.19.2.1.1.1.2.1.1
GSK @-@ 3 beta , glycogen synthase kinase 3 beta ; EC , embryonal carcinoma ; RA , retinoic acid ; DMEM , Dulbecco 's modified Eagle 's medium ; FBS , fetal bovine serum ; CM , conditioned medium ; PBS , phosphate @-@ buffered saline ; RT , reverse transcriptase ; PMSF , phenylmethylsulfonyl fluoride ; MAP2 , microtubule @-@ associated protein 2 ; GFP , green fluorescence protein ; EGFP , enhanced GFP ; CMV , cytomegalovirus ; Dox , doxycycline ; Tcf/ LEF , T cell factor/ lymphoid enhancer factor ; CKI , casein kinase I ; dpc , days post @-@ coitum ; rtTA , reverse tetracycline controlled transactivator ; ICAT , inhibitor of beta @-@ catenin and Tcf @-@ 4 .
SDL-AMR-09
bio.chicago_2015.17801
Rb
II
K46^mA
GAGA factor
NF-kB
PMC3437993
p
S1C
LiCl
bio.chicago_2015.19311
SDL-AMR-09
1-1.3 8-1.3.1.1.1 9-1.3.1.1 10-1.3.1.1.2.r 12-1.3.1.1.2.1.1 14-1.3.1.1.2 14-1.3.1.1.2.2 14-1.3.1.1.2.2.r 15-1.3.1.1.2.2.1.1 15-1.3.1.1.2.2.1.1.r 16-1.3.1.1.2.2.1 17-1.3.1.1.2.2.1.2.r 18-1.3.1.1.2.2.1.2.1.1 24-1.1 25-1.1.1.r 26-1.1.1.1.1 27-1.1.1.1 28-1.1.1 30-1 31-1.2.r 32-1.2.1.1 33-1.2
To identify the site( s ) on the cytoplasmic domain of the EGFR that mediates its recruitment of PI3K @-@ C2 beta , a panel of receptor point mutations was expressed in HEK293 cells .
MAPK
EGFR
HER3
5B
2
Site II seems to be generally less well conserved ( for example , Arp1 and beta @- and gamma @-@ tubulin ) , and this may explain why these target proteins bind less well to prefoldin than actin and alpha @-@ tubulin ( see Fig. 4 ; the fragments of Arp1 and beta @- and gamma @-@ tubulin also show binding to CCT , whereas actin and alpha @-@ tubulin do not ) .
SDL-AMR-09
0-1.2.1.1 1-1.2.1.1 2-1.2.1.1 3-1.2.1.1 4-1.2.1.1 5-1.2.1.1 6-1.2.1.1 7-1.2.1.1 8-1.2.1.1 9-1.2.1.1 10-1.2.1.1 11-1.2.1.1 12-1.2.1.1 13-1.2.1.1 14-1.2.1.1 15-1.2.1.1 16-1.2.1.1 17-1.2.1.1 18-1.2.1.1 19-1.2.1.1 20-1.2.1.1 23-1 23-1.1.1.1.2 23-1.1.1.1.2.2 23-1.1.1.1.2.2.r 24-1.2.1.2.1.1.1.2 25-1.2 26-1.2.1 26-1.3.1.2 27-1.2.1.2 27-1.2.1.2.1 27-1.2.1.2.1.r 28-1.2.1.2.1.1.1.2 29-1.2.1.2.1.1.1.1 30-1.2.1.2.1.1.1 31-1.2.1.2.1.1 32-1.2.1.2.1.1.3.1 33-1.2.1.2.1.1.3 34-1.2.1.2.1.1.2.r 35-1.2.1.2.1.1.2.1.1 36-1.2.1.2.1.1.3.2.r 37-1.2.1.2.1.1.3.2.1.1.1 38-1.2.1.2.1.1.3.2 39-1.2.1.2.1.1.3.2.2.1.1 41-1.1.1.1.2.2.1.1.1 41-1.1.1.1.2.2.2.1.1 41-1.2.1.2.1.1.3.2.2.1.1 43-1.3.1.3 44-1.3.1 45-1.3.1.1 48-1.3.1.2.1.1 49-1.3.1.2.1.1.1.r 50-1.3.1.2.1.1.1.1 51-1.1.1.1.2.2 52-1.1.1.1.2.2.1.1.1 54-1.1.1.1.2.2 55-1.1.1.1.2.2.2.1.1 57-1.1.1.1.2.2.2.1.1 57-1.2.1.2.1.1.3.2.2.1.1 58-1.3.1.2.1.4 59-1.3.1.2.1 59-1.3.1.2.1.3.1 60-1.3.1.2.1.2 61-1.3.1.2.1.2.2.r 62-1.3.1.2.1.2.2.1.1 64-1.3.1.2.1.3 65-1.2.1.2.1.1.3.2.1.1.1 67-1.2.1.2.1.1.3.2.2.1.1 69-1.1.1.1.2.2.2.1.1 69-1.2.1.2.1.1.3.2.2.1.1 71-1.3.1.2.1.3.1.1 71-1.3.1.2.1.3.1.1.r
bio.chicago_2015.19112
RAF
RAF_kinase
2
EGF
pmid_1528_0923.67
SDL-AMR-09
1-1 2-1.1.r 3-1.1 4-1.1.1.r 5-1.1.1.1.1 7-1.1.1.1.1 8-1.1.2.r 10-1.1.2.1.2.1 11-1.1.2.1.2.2 12-1.1.2 13-1.1.2
<sec-title level="2"> Differences in activity of ERK1 @/@ 2 in the breast cancer cell lines </sec-title>
15280923
GDP
Ras
GST-RBD
K46^mk
c2
GDP
4C
Tomlinson
2
14-3-3
24885690
SDL-AMR-09
By staining of senescence @-@ associated β-galactosidase activity [ @<xref ref-type="bibr" rid="B25"> 25 </xref>@ ] we examined whether the differential proliferation rates observed upon serum deprivation were attributable to cellular senescence .
1-1.3 2-1.3.1.r 3-1.3.1.1.1.1 5-1.3.1.1.1.1 6-1.3.1.1.1.2 7-1.3.1 10-1.3.2.1.1.1 13-1.1 14-1 15-1.2.1 15-1.2.1.r 17-1.2.2.1.2 18-1.2.2.1.1 19-1.2.2.1 20-1.2.2.1.3 22-1.2.2.1.3.1.1 23-1.2.2.1.3.1 27-1.2.2.2.1 28-1.2.2.2
a_pmid_2488_5690.57
Comparing these results with the level of pERK1 @/@ 2 indicated that there was no direct correlation between levels of these growth factor receptors and basal levels of ERK1 @/@ 2 phosphorylation .
15280923
pmid_1528_0923.75
SDL-AMR-09
0-1 1-1.1.1 2-1.1 2-1.1.2 2-1.1.2.r 3-1.2.r 5-1.2 9-1.2.1.1.1 10-1.3 14-1.3.1.1 14-1.3.1.1.r 15-1.3.1.4 16-1.3.1 18-1.3.1.2 19-1.3.1.2.1.r 20-1.3.1.2.1.2 21-1.3.1.2.1.1 22-1.3.1.2.1.1 23-1.3.1.2.1 25-1.3.1.3.1 26-1.3.1.3 28-1.2.1.1.1 28-1.3.1.3.2.1.1.1 30-1.2.1.1.1 30-1.3.1.3.2.1.1.1 31-1.2.1.2 31-1.3.1.3.2
10
m
CtBP2
pmid_1528_0923.105
1-1.3 2-1 3-1.1.r 4-1.1.1.1 5-1.2.r 6-1.2.1.1.1 8-1.2.1.1.1 9-1.2
<sec-title level="2"> Differential effect of PKI166 on ERK1 @/@ 2 phosphorylation </sec-title>
15280923
SDL-AMR-09
CtBP2
Ras
In another context , mutant B @-@ Raf induced cellular senescence rather than proliferation [ @<xref ref-type="bibr" rid="B23"> 23 </xref> , <xref ref-type="bibr" rid="B24"> 24 </xref>@ ] .
SDL-AMR-09
1-1.3.1 2-1.3 4-1.1 4-1.1.2 4-1.1.2.r 5-1.1.1.1 7-1.1.1.1 8-1 9-1.2.1 10-1.2 11-1.2.2 13-1.2.2.1 16-1.4.1.1.1.1 20-1.4.1.1.1.2
a_pmid_2488_5690.55
24885690
1-1.3.2 2-1.3 3-1.3.1.r 5-1.3.1.1 6-1.3.1 8-1.1.1.1.2.1 9-1.1.1 11-1.1 12-1 13-1.2.1.1 14-1.2.1 16-1.2 18-1.4.1
a_pmid_2488_5690.44
SDL-AMR-09
24885690
For structural confirmation of the deleted alleles , DNA sequencing was performed and all genotypes were verified ( Figure <xref ref-type="fig" rid="F1"> 1 </xref>@ B ) .
32
ERK
B-Raf
-
PI3KC2β
Cancer
cancer
U0126
ERBB3
K-Ras K-Ras4B
G469A
bio-kappa_0001.19
0-1.1.1.1.1 1-1.1 2-1.1.2.1.1 3-1.1.2.1.2 6-1.1.2 6-1.1.2.2 6-1.1.2.2.r 7-1.1.2.2.2 8-1.1.2.2.1.r 10-1.1.2.2.1.2.1.1 12-1.1.2.2.1.2.1.1 13-1.1.2.2.1.1.1.1.1 15-1.1.2.2.1.1 16-1.1.2.2.1 18-1.1.2.2.1.2.2.1.1 22-1.1.1.1.1 25-1.2.2.2 26-1.2.2 28-1.2 29-1.2.3.r 30-1.2.3.1 31-1.2.3 32-1.2.1.r 33-1.2.1 36-1.2.1.1.1.1.1 37-1.2.1.1.1.1.2 39-1.2.1.1.1.2 40-1.2.1.1 42-1.2.1.1.2 43-1.2.1.1.2.1.r 45-1.2.1.1.2.1
Grb2 contains SH3 domains that are bound constitutively to a carboxy - terminal proline - rich region of Sos , and the Grb2 ' 96 Sos complex is recruited to activated receptors by interactions between the SH2 domain of Grb2 and phosphotyrosine residues on the receptor .
SDL-AMR-09
1-1.1 1-1.2.2.1 3-1.1.1.1.1 4-1.2.1.1.1.1 4-1.2.1.1.1.2 7-1.2.1.1.1.3 8-1.2.1.1.1.3.1.r 10-1.2.1.1.1.3.1.1.1 11-1.2.1.1.1.3.1.1.1 12-1.2.1 14-1.2.1.1 15-1.2 17-1.2.2.1.1.1 18-1.2.2.1.1 19-1.2.1 23-1.2.2.1.1.3
SDL-AMR-09
To activate the Raf proteins , autoinhibition mediated by the N terminus must be relieved and the kinase domain must adopt the active catalytic conformation
bio.mskcc_0001.3
STAT3
Cdc14
PKI166
21
18
Cancer
cancer
Pin1
threonine
669
2
EGFR
Colorectal_cancer
colorectal cancer
1B
ERK12
C-Raf
Flag
5B
ERK
2+
e2
2B
V600E
BRAF
Drosophila
Drosophila
Ras
C-Raf
447
serine
ERK
CTD-S5-P
K-Ras K-Ras4B
1185
serine
B-Raf
0-1.1 1-1 2-1.2.r 4-1.2.2 5-1.2.2.1.r 6-1.2.2.1.1.1 7-1.2.2.2 9-1.2.1 9-1.2.1.r 10-1.2.4 11-1.2 13-1.2.3.1.1.1 14-1.2.3.1.1.2 15-1.2.3 18-1.2.5.2.1 20-1.2.5.2.2 21-1.2.5 25-1.3.1.2 27-1.3.1.2.1 29-1.3.1 30-1.3.1.1.1 32-1.3.1.1.2 35-1.3.1.3
bio.chicago_2015.19022
SDL-AMR-09
We found that the overexpression of SH3PX1 alone did not significantly affect the EGF receptor levels through a 60 @-@ min exposure to EGF ( Fig . 6 , lanes 9 @-@ 12 , upper panel ) .
LiCl
lysine
117
32
C-terminus
-
In contrast , S729A B @-@ Raf failed to heterodimerize with C @-@ Raf in response to growth factor treatment , and mutation of this site disrupted the constitutive interaction of oncogenic B @-@ Raf proteins and C @-@ Raf ( Fig . 3F ) , indicating that heterodimerization with C @-@ Raf is dependent on the C @-@ terminal S729 14 @-@ 3 @-@ 3 binding site of B @-@ Raf .
SDL-AMR-09
1-1 3-1.1.1.1.1.2.1 4-1.1.1.1.1.1.1 6-1.1.1.1.1.1.1 6-1.1.1.1.2.1.1 7-1.1.1 9-1.1.1.1 10-1.1.1.1.2.r 11-1.1.1.1.2.1.1 13-1.1.1.1.1.1.1 13-1.1.1.1.2.1.1 14-1.1.1.1.3.r 15-1.1.1.1.3 16-1.1.1.1.3.1.r 17-1.1.1.1.3.1.1 18-1.1.1.1.3.1.1 19-1.1.1.1.3.1 22-1.1.1.1.1 22-1.1.1.1.1.2 22-1.1.1.1.1.2.r 25-1.1.4.1.2.3 26-1.1.2 28-1.1.2.2.3 29-1.1.2.2 30-1.1.2.2.1.r 31-1.1.2.2.1 31-1.1.2.2.1.2 31-1.1.2.2.1.2.1.2.1 31-1.1.2.2.1.2.r 32-1.1.1.1.1.1.1 32-1.1.2.2.1.1.1 32-1.1.4.1.1.1.1.1 34-1.1.1.1.1.1.1 34-1.1.1.1.2.1.1 34-1.1.2.2.1.1.1 34-1.1.4.1.1.1.1.1 35-1.1.4.1.2.3 35-1.1.4.1.2.4.1 36-1.1 37-1.1.1.1.2.1.1 37-1.1.4.1.2.3.1.1 39-1.1.1.1.1.1.1 39-1.1.1.1.2.1.1 39-1.1.2.2.1.1.1 39-1.1.4.1.1.1.1.1 41-1.1.3.1 43-1.1.3.1.1 46-1.1.4 48-1.1.4.1.1 50-1.1.4.1.2.3.1.1 52-1.1.4.1.1.1.1.1 54-1.1.4.1 57-1.1.4.1.2.3.1.1 59-1.1.4.1.2.3.1.1 61-1.1.4.1.2.4.1.1.1 63-1.1.4.1.2.4.1.1.1 65-1.1.4.1.2.4.1.1.1 66-1.1.4.1.2.4 67-1.1.4.1.2.3 69-1.1.1.1.1.1.1 69-1.1.2.2.1.1.1 71-1.1.1.1.1.1.1 71-1.1.1.1.2.1.1 71-1.1.2.2.1.1.1
bio.mskcc_0001.26
2A
e2
-
Ras
B-Raf
Ras17N
p
2+
HER3
histidine
Pin1
Mek
Raf
HER2
EGFR
G4 box
14-3-3
0-1 2-1.1.1.1.1 3-1.1 6-1.1.2 7-1.1.2.1.r 8-1.1.2.1 9-1.1.2.1.1.r 10-1.1.2.1.1.1.1 12-1.1.2.1.1.1.1 13-1.1.2.2.2 14-1.1.2.2.2.1.1 16-1.1.2.2.2.2.1 17-1.1.2.2.2.1.2 17-1.1.2.2.2.2.2 18-1.1.2.2 19-1.1.2.2.1 20-1.1.2.2.1.1.r 21-1.1.2.2.1.1 23-1.1.2.3.1 23-1.1.2.3.1.r 24-1.1.2.3 29-1.1.2.4.2 31-1.1.2.4 32-1.1.2.4.1.1 32-1.1.2.4.1.1.r 33-1.1.2.4.1 34-1.1.2.4.1.2.r 35-1.1.2.4.1.2.2.1 37-1.1.2.2.2 38-1.1.2.5.2 39-1.1.2.5 40-1.1.2.5.1 41-1.1.2.5.1.1.r 42-1.1.2.5.1.1.1 43-1.1.2.5.1.1 44-1.1.2.2.r 44-1.1.2.5.1.2.r 45-1.1.2.5.1.2.2 46-1.1.2.5.1.2 46-1.1.2.5.1.2.1 46-1.1.2.5.1.2.1.r 47-1.1.2.5.1.2.1.1.r 48-1.1.2.5.1.2.1.1.1.1 49-1.1.2.5.3.r 50-1.1.2.5.3 51-1.1.2.5.3.1.r 52-1.1.2.5.3.1.1.1.1 53-1.1.2.5.3.1.1 54-1.1.2.5.3.1
SDL-AMR-09
Moreover , PLX4032 led to an increase in phosphorylation of FoxO1 @/@ 3A between 4 – 10 h after addition of compound ( not shown ) , which is known to promote its dissociation from DNA , and likely discards involvement of these factors as transcriptional regulators of HER3 in response to MAPK pathway inhibition .
bio-exp_0001.9
Brummer
JAK2
G12V
MEK
AMR-Role
Turke
151
serine
DNA
DNA
Interestingly , the ubiquitinated subfraction of wild @-@ type K @-@ Ras retained a significant amount of 32P @-@ GTP .
SDL-AMR-09
bio.bmtr_0001.12
0-1.3 3-1.1.3 4-1.1.4 6-1.1.2 8-1.1.2 9-1.1.1.1 11-1.1.1.1 12-1 14-1.2.3.1 15-1.2.3 16-1.2.3.r 17-1.2.2 17-1.2.2.1.1 19-1.2.1.1
1999
SDL-AMR-09
bio.mskcc_0001.24
To determine whether binding of 14 @-@ 3 @-@ 3 to B @-@ Raf is also required for heterodimerization , B @-@ Raf proteins containing lanine substitutions in the two 14 @-@ 3 @-@ 3 binding sites , S365 and S729 ( 2 ) , were examined for their abilities to heterodimerize with C @-@ Raf in response to growth factor treatment .
1-1.2 2-1.1.1 2-1.2.1.1 2-1.2.1.1.r 3-1.2.1.3 4-1.2.1.3.1.r 5-1.2.1.3.1 6-1.2.1.3.1 7-1.2.1.3.1 8-1.2.1.3.1 9-1.2.1.3.1 11-1.1.2.1.1.1 11-1.2.1.3.2.1.1 13-1.1.2.1.1.1 13-1.1.2.2.1.1 13-1.2.1.3.2.1.1 15-1.2.1.4 16-1.2.1 17-1.2.1.2.r 18-1.2.1.2 20-1.1.2.1.1.1 22-1.1.2.1.1.1 22-1.1.2.2.1.1 23-1.1.2.1.2.2.1.3.1 26-1.1.2.1.2 26-1.1.2.1.2.2 26-1.1.2.1.2.2.r 26-1.1.2.1.3 26-1.1.2.1.3.2 26-1.1.2.1.3.2.r 30-1.1.2.1.2.2.1.3.1.1.1 32-1.1.2.1.2.2.1.3.1.1.1 34-1.1.2.1.2.2.1.3.1.1.1 35-1.1.2.1.2.2.1.3 35-1.1.2.1.3.2.1.3 46-1 51-1.1.2 52-1.1.2.2.r 53-1.1.2.2.1.1 55-1.1.2.1.1.1 55-1.1.2.2.1.1 56-1.1.2.3.r 57-1.1.2.3 58-1.1.2.3.1.r 59-1.1.2.3.1.1 60-1.1.2.3.1.1 61-1.1.2.3.1
DPP
NAC
AZD6244
PI3
signal regulatory protein alpha
G12V
MAP2K2
MEK2
Rho
N-terminus
vMLC-1
GTP
EGFR
CD72
Together these results support the hypothesis that inhibition of ERK @-@ mediated phosphorylation of a conserved JM domain threonine residue leads to feedback activation of EGFR , HER2 , and ERBB3 ( Figure 7 ) .
0-1.1.2 1-1.1.3 2-1.1 2-1.1.1 2-1.1.1.r 3-1 5-1.2 6-1.2.1.r 7-1.2.1.1 8-1.2.1.1.1.r 9-1.2.1.1.1.2.1.1.1 11-1.2.1.1.1.2 12-1.2.1.1.1 13-1.2.1.1.1.1.r 15-1.2.1.1.1.1.2.2 16-1.2.1.1.1.1.2.1.1 17-1.2.1.1.1.1.2.1.2 18-1.2.1.1.1.1.1.1.1 19-1.2.1.1.1.1 20-1.2.1 21-1.2.1.2.r 22-1.2.1.2.2 23-1.2.1.2 24-1.2.1.2.1.r 25-1.2.1.2.1.1.1.1 27-1.2.1.2.1.2.1.1 29-1.2.1.2.1 30-1.2.1.2.1.3.1.1 32-1.3.1 33-1.3.1.1
SDL-AMR-09
bio.bmtr_0002.14
e
MDA-MB-231
2
thyroid cancer
Thyroid_cancer
B-Raf
Grb2
BCR
-
6
60
B-Raf
Erk-2
Axin
HER3
e
-
ubiquitin
MDA-MB-231
KSR1
threonine
SOCS3
bio.bmtr_0002.10
In cells transfected with wild @-@ type EGFR , MEK inhibition led to feedback activation of phospho @-@ ERBB3 and phosho @-@ EGFR , recapitulating the results we had observed in our panel of cancer cell lines ( Figure 6A ) .
SDL-AMR-09
1-1.3 2-1.3.1 3-1.3.1.1.r 4-1.3.1.1.2 6-1.3.1.1.2 7-1.3.1.1.1.1 9-1.1.1.1.1 10-1.1 11-1 12-1.2.r 13-1.2.2 14-1.2 15-1.2.1.r 16-1.2.1.1.2 16-1.2.1.2.2 18-1.2.1.1.1.1 19-1.2.1 22-1.2.1.2.1.1 22-1.3.1.1.1.1 24-1.4 26-1.4.1 26-1.4.1.1 26-1.4.1.1.r 27-1.4.1.2.1 29-1.4.1.2 30-1.4.1.2.2.r 31-1.4.1.2.2.2 31-1.4.1.2.2.2.r 32-1.4.1.2.2 33-1.4.1.2.2.1.r 34-1.4.1.2.2.1.1.2.1 35-1.4.1.2.2.1 36-1.4.1.2.2.1 38-1.5.1 39-1.5.1.1
H-Ras
vemurafenib
ERK
ERK
GAP
EGFR
U0126
e
-
e4
interrogative
H-Ras
MEK
CMV
Cot
729
serine
CD72
e2
0-1.1.3 2-1.1.1.1.1.2.1 2-1.1.2.1.1.2.1 3-1.1.1.1.1.1 4-1.1.1.1 7-1.1.1.1.1.3.1.1 9-1.1.1 10-1.1.1.2.r 12-1.1.1.2 12-1.1.1.2.1 12-1.1.1.2.1.r 14-1.1.1.3.1 16-1.1.1.3.1.1 18-1.1.1.1.1.3.1.1 20-1.1.1.1.2.1.1 22-1.1.1.1.2.1.1 22-1.1.2.1 25-1.1 26-1.1.2.1 28-1.1.2.1.1.2.1 29-1.1.2.1.1.1 30-1.1.2 31-1.1.2.2.r 32-1.1.2.2.1.1.1 33-1.1.2.2.1.1.2 34-1.1.2.2 37-1.1.2.2.2.1 38-1.1.2.2.2 40-1.1.1.3.1 42-1.1.1.3.1.1 44-1.1.2.1.2.1.1 46-1.1.2.1.2.1.1 48-1.1.2.1 48-1.1.2.1.2.1.1 51-1.1.2.2.r 52-1.2.3 55-1.2.3.1.1.1 56-1.2.2 56-1.2.3.1 58-1.2.1 59-1.2.1.1.r 60-1.2.1.1.1.2.1 61-1.2.1.1.1.1 62-1.2.1.1 63-1.2.1.1.2.r 64-1.2.1.1.2.1 65-1.2.1.1.2 66-1.2 69-1.2.2.1.1 70-1.2.2.2
Again , Ser 5 phosphorylation of the CTD is seen at the promoter ( Fig . 3 , CTD @-@ S5 @-@ P ) , whereas phosphorylation at Ser 2 increases as Pol II passes through the coding region ( Fig . 3 , CTD @-@ S2 @-@ P ) . As seen with the ADH1 gene , levels of Ser 2 phosphorylation in coding regions increased in the fcp1 mutants .
bio.chicago_2015.18065
SDL-AMR-09
CRB
EGFR
OB1
6
-
t
beta-catenin
Ras
B9
1997
Cdc25C
p2
The mutant proteins were then examined for their abilities to heterodimerize with C @-@ Raf and to bind activated Ras under conditions where feedback phosphorylation was induced ( in cycling cells for the G466A mutants and in cells treated with PDGF for 30 min for the WT B @-@ Raf mutants ) .
1-1.1.2.1.1.1 2-1.1.2.1.1 4-1.2 5-1 10-1.1.2.1 11-1.1.2.1.2.r 12-1.1.2.1.2.1.1 14-1.1.2.1.2.1.1 15-1.1.2 15-1.1.2.1.1.2.1 17-1.1.2.2 18-1.1.2.2.1.2 19-1.1.2.2.1.1.1 21-1.1.2.3.r 22-1.1.2.1.1.2.1.1.3.r 22-1.1.2.1.1.2.1.2.4.r 23-1.1.2.3.1.1 24-1.1.2.3.1 26-1.1.2.3 29-1.1.2.1.1.2.1.1.3.1 30-1.1.2.1.1.2.1.1.3 33-1.1.2.1.1.2.1.1.2.1 34-1.1.2.1.1.2.1.1 34-1.1.2.1.1.2.1.1.2 34-1.1.2.1.1.2.1.1.2.r 35-1.1.2.1.1.2.1 37-1.1.2.1.1.2.1.2.4 38-1.1.2.1.1.2.1.2.4.1 39-1.1.2.1.1.2.1.2.4.1.1.r 40-1.1.2.1.1.2.1.2.4.1.1.1.1 41-1.1.2.1.1.2.1.2.4.1.2.r 42-1.1.2.1.1.2.1.2.4.1.2.1 43-1.1.2.1.1.2.1.2.4.1.2.2 46-1.1.2.1.1.2.1.2.3 47-1.1.2.1.1.2.1.1.1.1 47-1.1.2.1.1.2.1.2.1.1 49-1.1.2.1.1.2.1.1.1.1 49-1.1.2.1.1.2.1.2.1.1 50-1.1.2.1.1.2.1.1 50-1.1.2.1.1.2.1.1.2 50-1.1.2.1.1.2.1.1.2.r
SDL-AMR-09
bio.mskcc_0001.39
65
n2
0-1.2 1-1.2.1 3-1.2.1.1 4-1.2.1.1 5-1.2.1.1 6-1.2.1.1 7-1.2.1.1 8-1.2.1.1 9-1.2.1.1 10-1.2.1.1 11-1.2.1.1 12-1 13-1.1.r 14-1.1.3.r 16-1.1.2 17-1.1.1 17-1.1.3.2 18-1.1 21-1.1.3.r 22-1.3 23-1.3.1.r 25-1.3.1.1.1.2 26-1.3.1.1.1.1.1 28-1.3.1.1.1.1.1 29-1.3.1.1 30-1.3.1 32-1.4.1.1 32-1.4.1.2 33-1.1.3.2.1.1 36-1.4.1
bio.ras_0003.5
SDL-AMR-09
Following purification , mono @- and di @- ubiquitinated K @-@ Ras appeared to be the major ubiquitination forms , which is consistent with the endogenous K @-@ Ras ubiquitination pattern ( Fig. 1 , A and B ) .
threonine
1179
K-Ras
alanine
trypsin
ADH1
Ras
Ras
14-3-3
protein kinase A
ERBB3
227
bio.bmtr_0003.13
Silencing of CtBP1 , and to a lesser extent CtBP2 , increased basal HER3 in 8505C cells , and markedly potentiated the effects of PLX4032 ( Fig . 5D and 5E ) .
SDL-AMR-09
0-1.1.1 1-1.1.1.1.r 2-1.1.1.1.1.1.1 4-1.1.1.1 7-1.1.1.1.2.2 7-1.1.1.1.2.2.1 7-1.1.1.1.2.2.1.r 9-1.1.1.1.2.1.1 11-1.1 12-1.1.2.2 13-1.1.2.1.1 14-1.1.3.r 15-1.1.3.1.1 16-1.1.3 18-1 18-1.3.1 19-1.2.3 22-1.2.1 23-1.2.1.1.r 24-1.2.1.1.1.1 26-1.3.1.1 26-1.3.1.2 28-1.3.1.1.1 29-1.3.1 30-1.3.1.2.1
EGFR
D594G
bio.bmtr_0005.17
0-1 1-1.1.1.1.3.1.1 2-1.1 4-1.1.1 6-1.1.1.1.2.1 7-1.1.1.1.1 8-1.1.1.2.r 9-1.1.1.2.1.1 10-1.1.1.3 11-1.1.1.3
SDL-AMR-09
Hence ASPP2 can be phosphorylated at serine 827 by MAPK1 in vitro .
HRG
HER3
-
K-Ras
EGF
HER3
0.5
UO126
beta-catenin
reporter gene
2B
p3
hKSR @-@ 2 selectively inhibited the Cot @-@ mediated activation of MEK by 60 % .
0-1.1.1.1 2-1.1.1.1 3-1.3 3-1.3.r 4-1 6-1.2.2.1.1.1 8-1.2.2 9-1.2 10-1.2.1.r 11-1.2.1.1.1 12-1.4.r 13-1.4.1 14-1.4
bio.bel_0002.11
SDL-AMR-09
2
s
interrogative
RafMekErk
U0126
ASPP2
Cdc25C
16
sIL-6R
HER3
Cancer
cancer
We identify four S/TP sites of B @-@ Raf phosphorylated by activated ERK and find that feedback phosphorylation of B @-@ Raf inhibits binding to activated Ras and disrupts heterodimerization with C @-@ Raf , which is dependent on the B @-@ Raf pS729 @/@ 14 @-@ 3 @-@ 3 binding site .
bio.mskcc_0001.1
0-1.1.1 1-1.1 2-1.1.2.1 4-1.1.2 6-1.1.2.3.1.1 8-1.1.2.3.1.1 9-1.1.2.2.1 11-1.1.2.2.1.1.2 12-1.1.2.2.1.1.1.1 13-1 14-1.2 16-1.1.2.2.1.2 17-1.1.2.2.1 17-1.2.2.2.2.3.1.3 19-1.1.2.3.1.1 21-1.1.2.3.1.1 22-1.2.2.1 23-1.2.2.1.2 25-1.2.2.1.2.2.2 26-1.2.2.1.2.2.1.1 27-1.2.2 28-1.2.2.2 29-1.2.2.2.2 30-1.2.2.2.2.2.r 31-1.2.2.2.2.2.1.1 33-1.2.2.2.2.2.1.1 37-1.2.2.2.2.3 40-1.1.2.3.1.1 42-1.1.2.3.1.1 42-1.2.2.2.2.2.1.1 45-1.2.2.2.2.3.1.4.1.1.1 47-1.2.2.2.2.3.1.4.1.1.1 49-1.2.2.2.2.3.1.4.1.1.1 50-1.2.2.1.2 50-1.2.2.2.2.3.1.4 51-1.1.2
SDL-AMR-09
GTP
GTP
MEK
6B
CD72
ASPP2
Cancer
cancer
JM domain
SUM149
This switch mechanism is common to a wide variety of GTP - binding proteins and is mediated by a conserved structure called the G - domain that consists of five conserved G boxes .
bio.ras_0001.4
SDL-AMR-09
0-1.2.2 1-1.2.1 2-1.2 4-1 5-1.1.r 7-1.1.2.1 10-1.1.1.1.1.1 12-1.1.1 13-1.1 17-1.3.r 19-1.3.2 19-1.3.3.3 21-1.3.1.r 23-1.3.1.1 25-1.3.1.1 27-1.3.3.r 29-1.3.3.1 30-1.3.2 31-1.3.1.1 31-1.3.3.2.1 32-1.3.3.2.2
G466A
-
lysine
117
Flag
2+
U0126
U0126
p3
retinoic acid
C-terminus
B-Raf
serine
5
ERK12
Extracellular_signal-regulated_kinases
PKI166
5
SDL-AMR-09
Alternatively , auxilin might bind much more weakly to Hsc70 in ADP than ATP .
0-1.2 0-1.2.r 2-1.1.1.1.1 3-1 4-1.1 4-1.1.5 5-1.1.3.1.1 6-1.1.3.1 7-1.1.3 8-1.1.2.r 9-1.1.2.1.1 10-1.1.4.r 11-1.1.4.1.1 12-1.1.5.r 13-1.1.5.3.1.1
bio.chicago_2015.18744
SDL-AMR-09
a_pmid_2488_5690.42
0-1.1.1.3 2-1.1.4.2 3-1.1.4.1.1 4-1.1.4.1 5-1.1.4 8-1.1.1.2.1.2.1.1 8-1.1.1.3.1.1.1 8-1.1.3.2.1.1.1.1 10-1.1.1.3 11-1.1.3.2.1 12-1.1.1.2.1 12-1.1.2.2.1 12-1.1.3.2.1 13-1.1.1.1.1 13-1.1.2.1.1 15-1.1.1.1.1 15-1.1.1.2.1.1 15-1.1.3.1.1 16-1.1 17-1.1.1.1.1 17-1.1.2.1.1 19-1.1.2.1.1 19-1.1.2.2.1.1 21-1.1.1.2.1.2.2.1.1.1 23-1.1.1.2.1.2.2 25-1.1.1.2.1.2.1.1 25-1.1.1.3.1.1.1 25-1.1.3.2.1.1.1.1 30-1.1.1.1.1 30-1.1.1.2.1.1 30-1.1.3.1.1 31-1.1 32-1.1.2.1.1 32-1.1.2.2.1.1 34-1.1 35-1.1 36-1.1 37-1.1.3.1.1 39-1.1.1.1.1 39-1.1.1.2.1.1 39-1.1.3.1.1 41-1.1.1.2.1.2.2.1.1.1 43-1.1.1.2.1.2.2 45-1.1.1.2.1.2.1.1 45-1.1.3.2.1.1.1.1 52-1 54-1.2.1 56-1.1.1.1.1 56-1.1.1.2.1.1 56-1.1.3.1.1
Out of these double positive clones , <i> BRAF </i> knockout cell lines RBO @-@ 1 and RBO @-@ 2 ( RKO @-@ derived <i> BRAF </i>@ <sup> onc/-/- </sup> 1 and 2 ) as well as RBW @-@ 1 ( RKO @-@ derived <i> BRAF </i>@ <sup> wt/-/- </sup> ) were established ( Figure <xref ref-type="fig" rid="F1"> 1 </xref>@ B ) .
24885690
B-Raf
-
13
15
1C
ERBB3
The Essential Activity of DSmurf Is Limited to the DPP Signaling Pathway
1-1.1.2 2-1.1 3-1.1.1.r 4-1.1.1.1.1 6-1 7-1.2.r 9-1.2.1.1 10-1.2.2 11-1.2
SDL-AMR-09
bio.chicago_2015.18724
Erk
vemurafenib
Grb2
s
24885690
0-1.2 1-1.2.1.1.1.1 2-1.2.1.1.1 3-1.2.1.1.2 3-1.2.1.1.2.3 3-1.2.1.1.2.3.r 4-1.2.1.1.2.2.1 5-1.2.1.1 6-1.2.1 7-1.2.1.2.2 8-1.2.1.2 11-1.1.1 12-1.1.1.1.r 13-1.1.1.1.1 14-1.1.1.1 16-1 18-1.1.3.1 19-1.1.3 20-1.1 21-1.1.2.r 22-1.1.2.1 23-1.1.2 26-1.3.1.1.1
SDL-AMR-09
a_pmid_2488_5690.66
Since virtually all malignant cancer cells show apoptosis resistance , the induction of apoptotic pathways is considered a particularly promising approach for therapeutic strategies [ @<xref ref-type="bibr" rid="B29"> 29 </xref>@ ] .
Wnt
ERBB
Because the mutations in PS1 apparently inhibit transcriptional activity of beta @-@ catenin downstream of GSK 3 beta , we hypothesized that PS1 may be interacting with the binding partner of beta @-@ catenin , namely hTcf @-@ 4 .
0-1.3 2-1.3.1.1 3-1.3.1.1.1.r 4-1.3.1.1.1 5-1.3.1.3 6-1.3.1 7-1.3.1.2.2 8-1.3.1.2 10-1.2.1.2.1.1.1.1 10-1.3.1.2.3.1.1.2 12-1.3.1.2.1 13-1.3.1.2.3.2 17-1.2.1.2.1.1.1.1 17-1.3.1.2.3.1.1.2 19-1.1 20-1 21-1.2.r 22-1.2.1.1.1.1 23-1.2 25-1.2.1 26-1.2.1.2.r 28-1.2.1.2.1 29-1.2.1.2 30-1.2.1.2.1.1.r 31-1.2.1.2.1.1.1.1 33-1.2.1.2.1.1.1.1 35-1.2.1.2.2 36-1.2.1.2.2.1.1.1 38-1.2.1.2.2.1.1.1
SDL-AMR-09
bio.chicago_2015.17718
K-Ras
6
2
Breast_cancer
breast cancer
68
threonine
e3
-
Pin1
2C
2
p
Grb2
ASH1
MAPK
serine
brinker
progesterone receptor
1A
ATM
NF1-333
interrogative
9
JNK
RAF
-
shRNA
epidermal growth factor
ERK12
pmid_1528_0923.83
SDL-AMR-09
15280923
0-1.1.1 1-1.1.1.1.r 2-1.1.1.1.2.1 9-1.1.1.1.1.1 12-1.1.1.1.2 13-1.1.1.1.2.3 14-1.1.1.1.2.4.r 15-1.1.1.1.2.4.1.1 16-1.1.1.1.2.4.1 17-1.1.1.1.2.4.1.2 18-1.1.1.1.2.4 18-1.1.2.1 19-1.1.1.1.2.4.2 20-1.1.1.1.2.4.2.1.r 21-1.1.1.1.2.4.2.1.1 22-1.1.1.1.2.4.2.1 23-1.1.1.1.2.4.2.1.2.r 24-1.1.1.1.2.4.2.1.2.2 25-1.1.1.1.2.4.2.1.2 30-1.1 32-1.1.2.2 32-1.1.2.2.1 32-1.1.2.2.1.r 33-1.1.2 35-1.1.2.1.1 43-1 44-1.2.1 45-1.2 46-1.2.2.r 47-1.2.2.1 48-1.2.2 50-1.2.1 51-1.3 52-1.3
Treatment with 0.5 <i> μ </i>@ <sc> M </sc> PKI166 , a concentration less than plasma and tumour concentrations achieved in preclinical models from oral administration of the drug , and the higher dose of 5.0 <i> μ </i>@ <sc> M </sc> , produced different levels of growth inhibition in different cell lines .
1B
ERK
2
e2
N-terminal
147
lysine
bel_pmid_1074_7872.21238
SDL-AMR-09
0-1.1.1.1.1 2-1 3-1.2.1 3-1.2.1.r 4-1.2.2.1.1 7-1.1 7-1.2 8-1.1.2.r 9-1.1.2 10-1.1.2.1.r 11-1.1.2.1.1.1 13-1.1.2.1.1.1 15-1.1.2.1.2.1.1 16-1.1.2.1.2 17-1.1.2.1.2.2 18-1.1.2.1.2.2.1.r 19-1.1.2.1.2.2.1.1.1.1.1.1 21-1.1.2.1.2.2.1.1.1.1.1.1 22-1.1.2.1.2.2.1 23-1.1.2.1.2.2.1.2.1.1.1.1 24-1.1.2.1.2.2.1.1.1 24-1.1.2.1.2.2.1.2.1 25-1.1.2.1.2.2.1.1 25-1.1.2.1.2.2.1.2
STAT3 , but not STAT5 , was activated in response to IGF @-@ I in 293T cells cotransfected with IGF @-@ IR and STAT expression vectors .
10747872
GI101A
ATM
This result suggests that Axin binding to both GSK @-@ 3 beta and beta @-@ catenin is necessary for inhibition of Lef @-@ 1 reporter gene transcription .
bio.chicago_2015.18186
0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 2-1 3-1.2.r 4-1.2.2.1.1.1 5-1.2.2 8-1.2.2.2.1.1.1 11-1.2.2.2.2.1.1 13-1.2.2.2.2.1.1 15-1.2.2.2.2.1.1 17-1.2 18-1.2.1.r 19-1.2.1 20-1.2.1.1.r 21-1.2.1.1.1.1.1 23-1.2.1.1.1.1.1 24-1.2.1.1.1.2 25-1.2.1.1.1 26-1.2.1.1
SDL-AMR-09
SDL-AMR-09
0-1.2.1 1-1.2 2-1.2.2.r 3-1.2.2 5-1 9-1.1.1 11-1.1.1.1.2 12-1.1.1.1.1.1.1 14-1.1.1.1.2.1 15-1.1.1.1.2.1.1.r 16-1.1.1.1.2.1.1.1 16-1.1.1.1.2.1.1.1.r 17-1.1.1.1.2.1.1.2 17-1.1.1.1.2.1.1.2.1 17-1.1.1.1.2.1.1.2.1.r 18-1.1.1.1.2.1.1 19-1.1.1.1.2.1.1.3.r 21-1.1.1.1.2.1.1.3
This series of reactions is reversed by rebinding of nucleotide , predominantly GTP , because of its higher concentration in the cell .
bio-kappa_0001.26
1
p
Rushworth
actin
SKBR3
C-Raf
C-Raf
9
12
B-Raf
bio.mskcc_0001.47
0-1.1.1 1-1.1 3-1 7-1.2.2.1.1.1 9-1.2.2.1.1.1 9-1.2.2.2.1.1 10-1.2.2 11-1.2.2.2.1.1 13-1.2.2.1.1.1 13-1.2.2.2.1.1 16-1.2 17-1.2.1.r 18-1.2.1.2.1.1.1 20-1.2.1.2 21-1.2.1.1 22-1.2.1
SDL-AMR-09
Previous studies have found that both the C @-@ Raf and B @-@ Raf proteins are targets of ERK @-@ dependent feedback phosphorylation
ERBB3PI3KAKT
PI3KAKT
PMC3847091
PKI166
megakaryocyte
extracellular signal-regulated kinase 1
RBOW
p2
neurite
e3
1
Pin1
293T
T cell factor lymphoid enhancer factor
CtBP2
GTP
-
Ras
H-ras
e3
serine
MDA-MB-435
orthophosphate
C-Raf
SDL-AMR-09
1-1.3 3-1.3.2 3-1.3.r 4-1.3.2.2.r 6-1.3.2.2.1 7-1.3.2.2.1 8-1.3.2.2 10-1.3.2.3 12-1.3.2.3.2 14-1.2.1.1.1 14-1.3.2.3.2.1.1.1.1 15-1.3.2.3.2.1 17-1.1 18-1 20-1.2 23-1.2.2.r 24-1.2.2.1.1.1.1 26-1.2.2.1 27-1.2.2 28-1.3.2.2.1 30-1.2.3.1.1 32-1.2.3 32-1.3.2.2
bio.bmtr_0004.12
To validate the use of an in vitro system to dissect the mechanism of Ras regulation , we measured the sensitivity of mUbRas to GAP @-@ mediated hydrolysis in a cellular reconstitution system .
BRAF
0-1.1 1-1.3 2-1 4-1.2 5-1.2.1.r 6-1.2.1.2.1.1 7-1.2.1 7-1.2.1.1 7-1.2.1.1.r 8-1.2.2.r 9-1.2.2.1.1.1.1 11-1.2.2.1 12-1.2.2
SDL-AMR-09
We next considered the effect of Ras monoubiquitination on GAP @-@ mediated hydrolysis .
bio.bmtr_0004.3
2
PI3KAKT
G5 box
reverse transcriptase
CK2
0.1
IL-3
multiple myeloma
U0126
p53
1997
ERK12
e2
HER2
RASRafMAPK
B-Raf
Peltenburg
3
Delta
PMC3515079
tyrosine
Tyrosine
n3
JAK
GAP
EGFR
MEK
10
Although STAT3 is essential for IL @-@ 6 @-@ induced macrophage differentiation of M1 cells , GATA @-@ 1 had little or no effect on tyrosine phosphorylation , DNA binding , and transcriptional activities of STAT3 in Western blot analysis , electropholic mobility shift assay ( EMSA ) , and luciferase assays .
SDL-AMR-09
0-1 1-1.2.1 2-1.2.1.r 3-1.2 4-1.2.2.r 5-1.2.2.2.1.1.1 7-1.2.2.2.1.1.1 9-1.2.2.2 10-1.2.2.3 11-1.2.2 12-1.2.2.1.r 13-1.2.2.1.1.1 14-1.2.2.1 16-1.1.1.1.1.1 18-1.1.1.1.1.1 20-1.1.1.3 21-1.1 22-1.1.2.1 22-1.1.2.1.r 23-1.1.1 23-1.1.2 24-1.1.1.2.r 25-1.1.1.2.1.1.1.1 26-1.1.1.2.1 28-1.1.1.2.2.1.2.1 29-1.1.1.2.2 31-1.1.1.2 32-1.1.1.2.3.2 33-1.1.1.2.3 34-1.1.1.2.3.1.r 35-1.1.1.2.3.1.1.1 36-1.1.3.r 37-1.1.3.1 38-1.1.3.1 42-1.1.3.2.1.1 43-1.1.3.2.1 44-1.1.3.2 49-1.1.3 50-1.1.3.3.1 51-1.1.3.3
10666199
bel_pmid_1066_6199.28424
B-Raf
cancer
Cancer
11
2+
Breast_cancer
breast cancer
200
threonine
Threonine
C-Raf
32
MAPK
GAP-43
threonine
669
1
breast cancer
Breast_cancer
EGFR
ERK
PKI166
GST-ASPP2
breast cancer
Breast_cancer
1A
n2
Ras
SDL-AMR-09
Formation of sharp borders of Iro @-@ C gene expression in response to localized EGFR signaling The lateral border delimiting Iro @-@ C expression in the wing disc is relatively straight and sharp ( e.g . Fig. 1B , Fig. 4C ) , raising the question of how such a well @-@ defined border can be established and maintained in response to EGFR signaling .
bio.chicago_2015.19345
0-1.1 1-1.1.1.r 2-1.1.1.1 3-1.1.1 4-1.1.1.2.r 5-1.1.1.2.1.1.1 7-1.1.1.2.1.1.1 8-1.1.1.2.1 8-1.2.1.1.2.1.1 9-1.1.1.2 11-1.1.2 14-1.1.2.1.1.1.1 15-1.1.2.1 17-1.2.1.1.1 18-1.2.1.1 19-1.2.1.1.2 20-1.2.1.1.2.1.1.1.1 22-1.2.1.1.2.1.1.1.1 23-1.2.1.1.2.1 24-1.2.1.1.2.2.r 26-1.2.1.1.2.2.1 27-1.2.1.1.2.2 29-1.2.1.2 30-1.2.1 31-1.2 31-1.2.3.1 32-1.2.2 36-1.2.3.1.1 37-1.2.3.1.1.1 39-1.2.3.1.2 40-1.2.3.1.2.1 43-1.2.4 45-1.2.4.1 46-1.2.4.1.1.r 47-1.2.4.1.1.1.r 48-1.2.4.1.1.1.1.1.2 50-1.2.4.1.1.1.1.1.1 52-1.2.4.1.1.1.1.1 53-1.2.4.1.1.1.1 54-1.2.4.1.1.1.3 56-1.2.4.1.1.1 58-1.2.4.1.1.2 60-1.1.2 60-1.2.4.1.1.1.2 62-1.1.2.1.1.1.1 62-1.2.4.1.1.1.2.1.1.1.1 63-1.1.2.1 63-1.2.4.1.1.1.2.1
p2
31
e2
Axin
5
Taken together , expression of CD72 most probably down @-@ modu @-@ lates phosphorylation of ERK induced by BCR signaling .
0-1.2 1-1.2.1 3-1.1.2.2 4-1.1.2.2.1.r 5-1.1.2.2.1.1.1 6-1.1.1 7-1.1 13-1.1.2.1 14-1.1.2.1.1.r 15-1.1.2.1.1.1.1 16-1.1.2.1.2 17-1.1.2.1.2.1.r 18-1.1.2.1.2.1.1.1.1 19-1.1.2.1.2.1
bel_pmid_1064_0734.39812
SDL-AMR-09
10640734
32
0-1.1.1.2 1-1.1.1.1.1 2-1.1.1.1 3-1.1.1 5-1 7-1.1 8-1.1.2.r 10-1.1.2 11-1.1.2.1.r 12-1.1.2.1.2 13-1.1.2.1.1 13-1.1.2.1.1.1 13-1.1.2.1.1.1.r 14-1.1.2.1
bio.bmtr_0004.20
SDL-AMR-09
This chemical ligation strategy will likely be useful for the study of other monoubiquitinated proteins .
beta-TrCP
FGF
G12V
-
PKI166
Cancer
cancer
RBOW
bio.chicago_2015.17892
Identification of the pathway directing TCF @-@ 1 import will be an important step in determining whether different mechanisms of LEF @-@ 1 and TCF @-@ 1 nuclear transport promote different LEF @-@ 1 , TCF @-@ 1 , and beta @-@ catenin function .
SDL-AMR-09
0-1.1 1-1.1.1.r 3-1.1.1 4-1.1.1.1 5-1.1.1.1.1.1.1.1 7-1.1.1.1.1.1.1.1 8-1.1.1.1.1 12-1.3 13-1 14-1.2.r 15-1.2 16-1.2.1.1 16-1.2.1.1.r 17-1.2.1.2.1 18-1.2.1.2 19-1.2.1.2.2.r 20-1.2.1.2.2.1.1.1.1 22-1.2.1.2.2.1.1.1.1 23-1.2.1.2.2.1 24-1.1.1.1.1.1.1.1 26-1.1.1.1.1.1.1.1 26-1.2.1.2.2.1.1.1.1 27-1.2.1.2.2.2 28-1.2.1.2.2 29-1.2.1 30-1.2.1.2.1 31-1.2.1.2.2.1.1.1.1 33-1.1.1.1.1.1.1.1 33-1.2.1.2.2.1.1.1.1 35-1.1.1.1.1.1.1.1 37-1.1.1.1.1.1.1.1 37-1.2.1.2.2.1.1.1.1 39-1.2.1.3.1 40-1.2.1.3.1.3.1.1 42-1.2.1.3.1.3.1.1 43-1.2.1.3
l
CK2
p4
2H
GST
Cancer
cancer
K-Ras
PKC
ubiquitin
TGF-b2
BCR
4
dCBP
ASPP2
ERBB3
HER3
BRAF
IL-11
S151A
p3
Ras
PP2A
Cdc25C
MAPK
Mek
2
SDL-AMR-09
bmtr_0006.1
A New Dimension to Ras Function : A Novel Role for Nucleotide @-@ Free Ras in Class II Phosphatidylinositol 3 @-@ Kinase Beta ( PI3KC2β) Regulation ( PMC3441633 )
1-1.1 2-1 4-1.2.1.1.1 5-1.2 8-1.3.1.1 9-1.3.1 10-1.3.1.2.r 11-1.3.1.2.2.1 13-1.3.1.2 13-1.3.1.2.2 13-1.3.1.2.2.r 14-1.3.1.2.1.1 15-1.3.1.3.r 16-1.3.1.3.2.2 17-1.3.1.3.2.2.1.1 18-1.3.1.3.2.1.1 19-1.3.1.3.2.1.2 21-1.3.1.3.2.1.2 22-1.3.1.3.2.1.3 25-1.3.1.3 27-1.4.1.1
SDL-AMR-09
0-1.1.1.1 1-1.1 1-1.1.2 1-1.1.2.r 3-1.1.3.1.1.1.1 5-1.1.3.1.1.1.1 6-1.1.3.1 7-1 9-1.2 11-1.2.2 12-1.2.2.2.1.1.1.1.1 14-1.2.2.2.1.1.1.1.1 15-1.2.2.2.1 15-1.2.2.2.1.1 15-1.2.2.2.1.1.r 16-1.2.2.2 18-1.3.r 19-1.3.r 20-1.3.1 21-1.3 22-1.3.2.1.1.1 25-1.3.2.2.1.1 27-1.3.2.2.1.1 29-1.3.2.2.1.1
Axin mutants with C @-@ terminal truncations lacked the ability to inhibit Lef @-@ 1 reporter activity , even though they bound GSK @-@ 3 beta and beta @-@ catenin .
bio.chicago_2015.17480
Ras
1-1.1.2 2-1.1.2 4-1 9-1.1.1.2 10-1.1.1.1.1.1 12-1.1.1.1.1.1 15-1.1.1.1.2.1.1 17-1.1.1.3.1.1 19-1.1.1.3.2.1 21-1.1.1.4 22-1.1.1.4.1.2 23-1.1.1.4.1.1.1.1.1 24-1.1.1.4.1.1.2 25-1.1 25-1.1.1.4.1.1 26-1.1.1 26-1.1.1.4.1
bio.bmtr_0005.10
An in vitro phophorylation assay was performed with a purified C @-@ terminus fragment of ASPP2 ( 693 @-@ 1128 ) containing both MAPK putative phosphorylation sites .
SDL-AMR-09
-
threonine
p
Mek12
SDL-AMR-09
bio.ras_0002.3
1-1.1 2-1.1.1.r 3-1.1.1.2 4-1.1.1.1 5-1.1.1 6-1 8-1.2.1 9-1.2 10-1.2.1.1.r 11-1.2.1.1 13-1.2.1.1.2.3 14-1.2.1.1.2.2 15-1.2.1.1.2 15-1.2.1.1.2.1 15-1.2.1.1.2.1.r 17-1.3.1.1.1
The enhancement of specific effector pathways plays a critical role in maintaining an appropriate biological response ( 8 ) .
1
RASSF
GDP
RKO
E2F
2
1
pmid_1528_0923.106
SDL-AMR-09
To evaluate whether the antiproliferative effects of EGFR inhibition involve ERK1 @/@ 2 activation , the status of pERK1 @/@ 2 was determined in cells exposed to the same concentrations of PKI166 used for the growth inhibition assays , in the presence and absence of U0126 ( 10 <i> μ </i>@ <sc> M </sc> ) ( <xref ref-type="fig" rid="fig5"> Figure 5 </xref> ) .
1-1.3 2-1.3.1.1 2-1.3.1.1.r 4-1.3.1.2.2 4-1.3.1.2.2.1 4-1.3.1.2.2.1.r 5-1.3.1.2 6-1.3.1.2.1.r 7-1.3.1.2.1.1.1.1 8-1.3.1.2.1 9-1.3.1 10-1.3.1.3.1.1.1 12-1.3.1.3.1.1.1 13-1.3.1.3 16-1.1 20-1.1.1.1.1 20-1.3.1.3.1.1.1 22-1 23-1.2.r 24-1.2 25-1.2.1 26-1.2.1.1.r 28-1.2.1.1.2 29-1.2.1.1 29-1.2.1.2.1.1.2 30-1.2.1.1.1.r 31-1.2.1.1.1.1.1 32-1.2.1.1.1.2 33-1.2.1.1.1.2.1.r 35-1.2.1.1.1.2.1.1.1 36-1.2.1.1.1.2.1.1 37-1.2.1.1.1.2.1 39-1.2.1.2.r 41-1.2.1.2.1 42-1.2.1.2 43-1.2.1.2.2 44-1.2.1.2.1.1.r 45-1.2.1.2.1.1.1.1 47-1.2.1.2.1.1.2.1 57-1.4.1 58-1.4.1.1
15280923
HER2
PIK3CA
28
30
Cancer
cancer
n3
SDL-AMR-09
To determine whether in vitro phosphorylation of fascin with PKC occurs at the same sites as observed in vivo , two @-@ dimensional phosphopeptide mapping was performed .
bio.chicago_2015.17275
1-1.2 2-1.2.1.1 2-1.2.1.1.r 3-1.2.1.4 4-1.2.1.4 5-1.2.1 6-1.2.1.2.r 7-1.2.1.2.1.1 8-1.2.1.3.r 9-1.2.1.3.1.1 11-1.2.1.5.r 13-1.2.1.5.1 14-1.2.1.5 14-1.2.1.5.1.1 15-1.2.1.5.1.1.2.r 16-1.2.1.5.1.1.2 17-1.2.1.5.1.1.2.1 18-1.2.1.5.1.1.2.1 20-1.1.2.1 22-1.1.2 23-1.1.1.1.1 24-1.1 26-1
threonine
669
pmid_1528_0923.87
1-1.2.1.1 2-1.2 4-1 5-1.1.1.1.1 6-1.1 8-1.1.2.1 9-1.1.2 10-1.1.2.2.r 11-1.1.2.2.1.1 14-1.3.1 15-1.3.1 17-1.3 18-1.3.2.1.3.1 19-1.3.2.1.3 20-1.3.2.1.2 21-1.3.2.1 22-1.3.2.1.1.r 23-1.3.2.1.1.2.1 30-1.3.2 31-1.3.2.2.2.1 32-1.3.2.2.2 33-1.3.2.2 34-1.3.2.2.1.r 35-1.3.2.2.1.2.1 42-1.3.2.1.1.1.1 42-1.3.2.2.1.1.1
The SKBR3 cells , expressing EGFR and also high levels of HER2 , were most sensitive , showing 55 % growth inhibition with 0.5 <i> μ </i>@ <sc> M </sc> and 76 % inhibition with 5.0 <i> μ </i>@ <sc> M </sc> PKI166 .
15280923
SDL-AMR-09
Raf
Ras
2H
G1 box
B-Raf
671
carcinoma
BRAF
MTT
3A
Cancer
cancer
B-Raf
SDL-AMR-09
bio.bmtr_0001.18
To ensure that ubiquitinated Ras was being detected , the protein pulled down by GST @-@ RBD was subjected to a second affinity purification on a cobalt column to purify the Flag @-@ His @-@ tagged K @-@ Ras .
1-1.3 2-1.3.2.r 3-1.3.2.1.2 4-1.3.2.1.1.1 7-1.3.2 10-1.1 10-1.2.5.2.2.1.2 11-1.1.1 12-1.1.1 13-1.1.1.1.r 14-1.1.1.1.1.1 16-1.1.1.1.1.1 18-1 21-1.2.2 21-1.2.2.1 21-1.2.2.1.r 22-1.2.3 23-1.2 23-1.2.5 23-1.2.5.r 26-1.2.4.1 27-1.2.4 29-1.2 29-1.2.5 29-1.2.5.r 31-1.2.5.2.2.1.1.1.1 35-1.2.5.2.2 36-1.2.5.2.1.1 38-1.2.5.2.1.1
B-Raf
PKI166 inhibited ligand @-@ induced EGFR phosphorylation in a dose dependent manner in these four cell lines , and also phosphorylation of HER2 in SKBR3 cells , in the absence or presence of 50 ng ml @<sup> −1 </sup> EGF ( <xref ref-type="fig" rid="fig2"> Figure 2 </xref> ) ( data for other cell lines not shown ) .
pmid_1528_0923.90
SDL-AMR-09
15280923
0-1.1.1.1.1 1-1.1 1-1.2 2-1.1.2.2.1 4-1.1.2.2 5-1.1.2.1.1.1 6-1.1.2 7-1.1.3.r 9-1.1.3.1 10-1.1.3 12-1.1.4.r 13-1.1.4.2 14-1.1.4.1 15-1.1.4 16-1.1.4 18-1 20-1.2.1 21-1.2.1.1.r 22-1.2.1.1.1.1 23-1.2.1.2.r 24-1.2.1.2.1.1 25-1.2.1.2 29-1.2.2.2 30-1.2.2 32-1.2.2.r 33-1.2.2.1.2.1 34-1.2.2.1.2.2 35-1.2.2.1.2.2 39-1.2.2.1.1.1 42-1.3.1 43-1.3.1.1 47-1.4.2 48-1.4.2.1.r 49-1.4.2.1.1 50-1.4.2.1 51-1.4.2.1 52-1.4.1 52-1.4.1.r 53-1.4
1C
RASMAPK
MEK
Wntbeta-catenin
AMR-EntityType
AMR-Term
caldesmon
B-Raf
C-Raf
chromatin
CD11b
PKI166
f
Regulation of Dpp Targets by brinker .
0-1 1-1.2.r 2-1.2.1.1.1.1 3-1.2 3-1.2.1 3-1.2.1.r 4-1.1.r 5-1.1.1.1
bio.chicago_2015.18747
SDL-AMR-09
bio.bmtr_0003.21
SDL-AMR-09
1-1.1.2.1 2-1.1.2 3-1.1.2.2 9-1.1.2.2.1.1.1.1.1 10-1.1.2.2.1.1 12-1.1.1 12-1.1.1.r 14-1.1 16-1 17-1.2.1.1.1 17-1.2.1.1.1.1 17-1.2.1.1.1.1.r 17-1.3.1.1.1.1.r 18-1.2.1.1 20-1.2 22-1.2.1 24-1.2.1.2.2 25-1.2.1.2 29-1.2.1.3.r 30-1.2.1.3.1 31-1.2.1.3.1.2.r 33-1.2.1.3.1.2 34-1.2.1.3 36-1.2.1.3.2 38-1.2.1.3.2.2.r 39-1.2.1.3.2.2 41-1.3.1.1.1.1 43-1.3.1.1.1.2
The biochemical mechanisms involved in delocalization of CtBPs by MAPK inhibition have not been explored , but posttranslational modifications are known to regulate the repressive activity of CtBPs either by translocation to the cytoplasm or by targeting them for degradation ( 36 , 37 ) .
RafMEKERK
-
Yu
K-Ras
cyclin E
5
lysine
117
bio.chicago_2015.19306
SDL-AMR-09
Dissected wing imaginal discs stained with antibodies against the beta @-@ galactosidase and Engrailed proteins showing the induction and suppression of induction of Engrailed expression ; anterior upward , wing pouch to the left .
0-1.5 1-1.4 2-1.6 3-1 4-1.1 5-1.1.1.r 6-1.1.1 7-1.1.1.1 9-1.1.1.1.1.1.1.1 11-1.1.1.1.1.1.1.1 12-1.1.1.1.1 13-1.1.1.1.1.2.1.1 14-1.1.1.1.1.2 15-1.2 17-1.2.1.2.1 18-1.2.1 19-1.2.1.2 21-1.2.1.2.1 23-1.2.1.1.1.1 24-1.2.1.1.1 26-1.3.1.2 27-1.3.1.2.1 29-1.3.1.3 30-1.3.1 33-1.3.1.1
SKBR3
Lukas
B-Raf
protein phosphatase 2A
FoxO13A
PLX4032
ASPP2
DSmurf
4A
Ras
-
Ras
CRB
SDL-AMR-09
0-1.2.1.r 2-1.2.1.1 3-1.2.1.1.1.r 4-1.2.1.1.1.1.1 5-1.2.1.1.2.r 6-1.2.1.1.2.1.1.1 7-1.2.1.1.2 8-1.2.1.1.2.2.1 9-1.2.1.1.2.2 11-1.2.1 13-1.3 14-1 14-1.1 14-1.1.r
How the interactions of filamin with actin and transmembrane proteins are regulated is largely unknown .
bio.chicago_2015.19083
epsilon
5
Shc
ERBB3
1
ERK12
cyclin-dependent kinase
CD72
p2
2+
5E
293T
hTcf-4
p2
1-1.3 4-1.3.1.r 5-1.3.1.1.1 6-1.3.1.1 7-1.3.1 9-1.3.1.2 12-1.1.2 13-1.1.1.1 14-1.1 16-1 17-1.2.r 18-1.2 20-1.2.2.1 21-1.2.2 23-1.2.2.2 27-1.2.2.2.1.1 27-1.2.2.2.1.2 28-1.2.2.2.1.1.1.r 29-1.2.2.2.1.1.1.1.1 30-1.2.2.2.1 31-1.2.2.2.1.2.1.1.1
SDL-AMR-09
bio.mskcc_0001.5
Once activated , either by upstream signaling or by mutational events , all Raf proteins are capable of initiating the phosphorylation cascade that results in the sequential activation of MEK and ERK .
1-1.5 2-1.5.1.r 3-1.5.1 4-1.5.1.1 6-1.1.2 6-1.1.2.1 6-1.1.2.1.r 7-1.1.1.1 7-1.4.1.1 9-1.1.1.1 9-1.4.1.1 11-1.3 12-1 13-1.4.r 15-1.4.2 15-1.4.2.1 15-1.4.2.1.r 16-1.2.2.1 18-1.2.2.1.1.1 20-1.2.2 21-1.2.1.1.1 22-1.2
bio.bmtr_0004.14
SDL-AMR-09
As seen in Figure 5c , monoubiquitinated K @-@ Ras is less sensitive than the unmodified protein to GAP @-@ mediated GTP hydrolysis .
MEK
n3
ubiquitin
Ras
These findings were confirmed in a second cell line ( Supplementary Fig. S5A ) .
SDL-AMR-09
0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 3-1 4-1.2.r 6-1.2.1 6-1.2.1.1 6-1.2.1.1.r 7-1.2 8-1.2 10-1.3.1.2 11-1.3.1 12-1.3.1.1
bio.bmtr_0003.16
19
Ras
bio.bmtr_0005.6
3-1.2.1.1 4-1.2.1 5-1.2.2 6-1.2 8-1.2.3.1.1.1 9-1.2.3 12-1.1.1.1 14-1.1.1.1 15-1.2
One of the most studied downstream pathways of RAS signalling is the Raf @-@ MAPK pathway .
SDL-AMR-09
Chk2
CNTF
4
20
45
-
365
serine
p3
DNA
DNA
70
CD72
-
395
serine
s3
31
steroidnuclear receptor
C-Raf
STAT3
Axin
K-Ras
IkB
GAP
Inhibition of GSK @-@ 3 beta @-@ dependent phosphorylation of Axin by Dvl .
bio.chicago_2015.18091
0-1 1-1.1.r 2-1.1.3.1.1.1 7-1.1.3 8-1.1 9-1.1.1.r 10-1.1.1.1.1 11-1.1.2.r 12-1.1.2.1.1
SDL-AMR-09
RKO
S5A
MEK
30
These results demonstrate that EGFR T669 phosphorylation is necessary for MEK @/@ ERK to suppress EGFR @-@ mediated activation of ERBB3 .
bio.bmtr_0002.20
0-1.1.1 1-1.1 1-1.1.2 1-1.1.2.r 2-1 3-1.2.r 4-1.2.2.1.3.1.1 6-1.2.2 8-1.2 9-1.2.1.r 10-1.2.1.1.1.1 12-1.2.1.1.1.1 14-1.2.1 15-1.2.1.2.2.1.1.1 17-1.2.1.2.2 18-1.2.1.2 19-1.2.1.2.1.r 20-1.2.1.2.1.1.1
SDL-AMR-09
HEK293T
Axin
ATM
T669A
1994
V600E
0.5
choline
tyrosine
e
HER3
f
14
16
4
sorafenib
6A
threonine
ASPP2
ATF-2
rtTA
SUM149
0-1 0-1.1 0-1.1.r 1-1 1-1.1 1-1.1.r 3-1.1.1.1 4-1.1.1.1.1.r 5-1.1.1.1.1.1.1 7-1.1.1.1.1.1.1 8-1.1.1 9-1.1 10-1.1.2 11-1.1.1.2.3.1 13-1.1.1.2.3 14-1.1.1.2 15-1.1.1.2.1.r 16-1.1.1.2.1.1.1 17-1.1.1.2.2.r 18-1.1.1.2.2.1 20-1.1.1.2.2.1 21-1.1.1.2.2.2 22-1.1.1.2.2
In addition , introduction of B @-@ Raf enhances and sustains integrin @-@ mediated activation of ERK in wild @-@ type primary fibroblasts
SDL-AMR-09
bio.bel_0002.5
Raf
-
DAT
26
0-1 1-1.1.1.1.1.1 3-1.1.1.1.1.1 4-1.1 6-1.1.1 8-1.1.1.2.1.1.1.1 9-1.1.1.2.1 10-1.1.1.2.1.2.1.1 11-1.1.1.2 13-1.2.1.2 14-1.2.1.1 15-1.2.1 18-1.2.1.1.1.1 19-1.2.1.1.1.1 20-1.2.1.1.1 22-1.2 23-1.2.2.r 25-1.2.2 26-1.2.2.1.r 27-1.2.2.1 28-1.2.2.1 31-1.2.3 36-1.2.3.1 38-1.2.3.1.2.1.1.1.1 39-1.2.3.1.2.1 41-1.2.1.1.1 42-1.2.1.1 43-1.2.3.1.2 43-1.2.3.1.3
SDL-AMR-09
pmid_1528_0923.73
Since ERK1 @/@ 2 can be activated via EGFR and HER2 signalling , relative expression levels of these growth factor receptors were measured in the panel of cell lines , to test if there was a correlation between ERK activation and receptor expression levels .
15280923
RAS
Bray
1
SDL-AMR-09
15280923
To demonstrate inhibition of EGFR and HER2 phosphorylation by the concentrations of PKI166 used for the growth inhibition assays , cell lysates were prepared from MDA @-@ MB @-@ 231 , MDA @-@ MB @-@ 468 , SUM149 and SKBR3 cells after treatment with PKI166 and stimulation with EGF , and phosphorylation of the receptors assessed .
1-1.3 2-1.3.1 3-1.3.1.2.r 4-1.3.1.2.1.1.1.1 5-1.3.1.2.1 6-1.3.1.2.1.2.1.1 7-1.3.1.2 8-1.3.1.1.r 10-1.3.1.1 10-1.3.1.1.2 10-1.3.1.1.2.r 12-1.3.1.1.1.1 13-1.3.1.1.2.1 14-1.3.1.1.2.1.1.r 16-1.3.1.1.2.1.1.1.1 17-1.3.1.1.2.1.1.1 18-1.3.1.1.2.1.1 20-1.1.1.1 21-1.1.1 23-1.1 24-1.1.2.r 25-1.1.2.1.1.1 25-1.1.2.2.1.1 27-1.1.2.1.1.1 27-1.1.2.2.1.1 29-1.1.2.1.1.1 31-1.1.2.1.1.1 31-1.1.2.2.1.1 33-1.1.2.1.1.1 33-1.1.2.2.1.1 35-1.1.2.2.1.1 37-1.1.2.3.1.1 38-1.1.2 39-1.1.2.4.1.1 40-1.1.2.1 40-1.1.2.2 40-1.1.2.3 40-1.1.2.4 41-1.1.3 42-1.1.3.1.1 43-1.1.3.1.1.1.r 44-1.1.3.1.1.1.1.1 45-1.1.3.1 46-1.1.3.1.2 47-1.1.3.1.2.1.r 48-1.1.3.1.2.1.1.1 51-1.2.1 52-1.2.1.1.r 54-1.2.1.1 55-1.2
pmid_1528_0923.89
MDA-MB-231
p4
ERK12
U2AF65
e
SHOC2
ERK
C-Raf
BR
GTP
Ras
2
Ras
GTP
Erk
HER2
PI3K
1
Ras17N69N
ERK12
r3
D594G
24885690
SDL-AMR-09
Sustained proliferative signaling is considered one of the major traits of cancer cells and is therefore used as a target mechanism of individualized therapy approaches including anti EGFR therapy strategies in colorectal cancer [ @<xref ref-type="bibr" rid="B21"> 21 </xref> , <xref ref-type="bibr" rid="B22"> 22 </xref>@ ] .
a_pmid_2488_5690.54
0-1.1.1.2 2-1.1.1 4-1 8-1.1.2.2 9-1.1.2 10-1.1.2.1.r 11-1.1.2.1.1.2.1 12-1.1.2.1 15-1.2 16-1.2.1 17-1.2.1.2.r 19-1.2.1.2.1 20-1.2.1.2 21-1.2.1.2.2.r 22-1.2.1.2.2.1.1 23-1.2.1.2.2.1 24-1.2.1.2.2 25-1.1 25-1.2.1.2.2.2 26-1.2.1.2.2.2.1.1.1 27-1.2.1.2.2.2.1.1.1.1.1.1 28-1.2.1.2.2.2.1.1 29-1.2.1.2.2.2.1 30-1.2.1.2.2.2.1.2.r 31-1.2.1.2.2.2.1.2.2.1 32-1.1.2.1.1.2.1 32-1.2.1.2.2.2.1.2.2.2 35-1.3.1.1.1 39-1.2.1.2.2.2.2.1.1.1
etoposide
Dpp
Notch
trypsin
B-RAF
Ras
3B
s
27
7A
MAPK inhibition may dictate a chromatin redistribution of these repressors , and thus activate HER3 transcription .
SDL-AMR-09
0-1.1.1.1.1.1 1-1.1.1 2-1 3-1.1 5-1.1.2.2 6-1.1.2 7-1.1.2.1.r 8-1.1.2.1.1 9-1.1.2.1 9-1.1.2.1.2 9-1.1.2.1.2.r 12-1.2 13-1.2.1 14-1.2.1.2.1.1.1 15-1.2.1.2
bio.bmtr_0003.20
1B
MDA-MB-231
Ras
MAP
While it is difficult to eliminate this possibility , it is unlikely since , as shown in fig. S1B , the T35 mutant of K @-@ Ras , which fails to interact with downstream effectors ( fig . S1B ) undergoes comparable monobuiquitination to wild type Ras .
0-1 2-1.1.1.r 3-1.1 5-1.1.1 6-1.1.1.1 7-1.1.1.1.1 9-1.2.2 10-1.1.1.r 11-1.2 11-1.2.1 11-1.2.1.r 11-1.2.3.1.2.3.1 12-1.2.3 15-1.2.3.1.3 16-1.2.3.1.3.1.r 17-1.2.3.1.3.1 18-1.2.3.1.3.1.1 21-1.2.3.1.2.2.1 22-1.2.3.1.2 22-1.2.3.1.2.2 22-1.2.3.1.2.2.r 24-1.2.3.1.2.1.1 26-1.2.3.1.2.1.1 31-1.2.3.1.2.3 32-1.2.3.1.2.3.2.r 33-1.2.3.1.2.3.2.1 34-1.2.3.1.2.3.2 38-1.2.3.1.3.1.1 41-1.2.3.1.4 44-1.2.3.1.4.1.1.2 45-1.2.3.1.4.1.1.2 46-1.2.3.1.4.1.1.1.1
bio.bmtr_0001.15
SDL-AMR-09
DNA
DNA
To this end we compared the rate of GTP hydrolysis for Ras and mUbRas in the presence of the catalytic domains of two GAPs , NF1 ( NF1 @-@ 333 ) and p120GAP( GAP @-@ 334 ) .
SDL-AMR-09
1-1.4 3-1.1 4-1 6-1.2 6-1.3 8-1.2.1.1.1.1 8-1.3.1.1.1.1 9-1.2.1 9-1.3.1 11-1.2.1.1.2.1.1.1 11-1.3.1.1.2.1.1.1 12-1.2.1.2.1 16-1.2.1.2 17-1.2.1.2.1.r 19-1.2.1.2.1.3 20-1.2.1.2.1.1 20-1.2.1.2.1.2 23-1.2.1.2.1.1.2.2.1.1.1 25-1.2.1.2.1.1.2.1.1 27-1.2.1.2.1.1.2.1.1 29-1.2.1.2.1.1.1.1 31-1.2.1.2.1 33-1.2.1.2.1.2.1.1 35-1.2.1.2.1.2.1.1
bio.bmtr_0004.4
ATF CREB
SDL-AMR-09
bel_pmid_1085_1026.8694
0-1.3.r 1-1.3.1.3 2-1.3.1.1.1 3-1.3.1 4-1.3.1.2.1.1.1 5-1.3.1.1 5-1.3.1.2 7-1.3 9-1.3.2 11-1.1.1.1.1 12-1.1.1.1.2 13-1.1 14-1.1.2 15-1.1.2.1.r 16-1.1.2.1.1.1 17-1.1.2.1.1.2 19-1 20-1.2
10851026
When either primary or OB1 osteoblasts are induced to differentiate , FGF signaling inhibits expression of alkaline phosphatase , and blocks mineralization .
MEK
STAT3
2A
B-Raf
GTP
Hirano
Cancer
cancer
breast cancer
Breast_cancer
0-1.3.r 1-1.3.1 1-1.3.1.r 2-1.3.2.1.1 4-1.3.2.1.1.1 5-1.3.2.1 6-1.3.2 8-1.3.2.2 11-1.1.2.2.1 12-1.1.2.2.2 13-1.1 14-1.1 15-1.1.1.1 16-1 18-1.2.2 23-1.2.1.1.1.1 25-1.2.1.1 26-1.2.1 36-1.2.3.1.1.1.1 37-1.2.3.1.1.1.2 39-1.2.3.1.1.1.2 40-1.2.3.1.1 41-1.2.3.1.1.2.1 42-1.2.3.1.1.2.2 43-1.2.3.1.1.1 43-1.2.3.1.1.2 46-1.2.3.1.2.1 47-1.2.3.1.2 50-1.4.1.1.1
a_pmid_2488_5690.38
24885690
Despite its near @-@ diploid karyotype and MSI phenotype , the colorectal cancer cell line RKO carries a stable triplication of the <i> BRAF </i> gene locus ( dup ( 7 ) ( q21q36 )) with one wild @-@ type and two mutant alleles present in parental cells [ @<xref ref-type="bibr" rid="B13"> 13 </xref>@ ] .
SDL-AMR-09
1.4
CtBP1
827
G466A
Rheb
RKO
NGA
Rlf
receptor tyrosine kinase
-
pmid_1528_0923.91
1-1.1.2 2-1.1.1.1.1 4-1.1.1.1.1 5-1.1 8-1.2.1 9-1.2.2 10-1.2 11-1.2.2.1.r 12-1.2.2.1 13-1.2.2.1.1.r 14-1.2.2.1.1.1.1
<sec-title level="2"> Constitutive ERK1 @/@ 2 phosphorylation as a potential escape mechanism from inhibition by PKI166 </sec-title>
SDL-AMR-09
15280923
ERK
1B
1-1.2 2-1.2.1.r 4-1.2.1 4-1.2.1.1 4-1.2.1.1.r 6-1.1 6-1.1.r 7-1 8-1.3.r 8-1.4 9-1.3 10-1.3.1.r 11-1.3.1.2 12-1.3.1.1.1 14-1.3.1.1.1 17-1.4.1.r 19-1.4.1.3 21-1.4.1.1 21-1.4.1.1.r 22-1.4.1 23-1.4.1.2.r 24-1.4.1.2 27-1.5.1 28-1.5.1.1
pmid_1528_0923.113
The effects of the inhibitors were not related to downregulation of total ERK1 @/@ 2 proteins , as the levels did not decrease with treatment ( <xref ref-type="fig" rid="fig5"> Figure 5 </xref> ) .
SDL-AMR-09
15280923
B-Raf
FGFR3
PUMA
RAFTK
ubiquitin
1
Ras
guanine nucleotide exchange factor
bio-kappa_0001.11
As a positive regulator , PP2A associates with C @-@ Raf and Ksr1 and dephosphorylates negative regulatory sites on both proteins , allowing their recruitment to the membrane and leading to Mek and Erk activation .
5-1.1.1.1.1 6-1.1 7-1.1.2.r 8-1.1.2.1.1.1 10-1.1.2.1.1.1 12-1.1.2.2.1.1 13-1.2.1.2 15-1.2.1.1 16-1.2.1.1 17-1.2.1 20-1.2.1 22-1.3 23-1.3.1.1 23-1.3.1.1.r 24-1.3.1 25-1.3.1.2.r 27-1.3.1.2 28-1 28-1.1.2 29-1.4 30-1.4.1.r 31-1.4.1.1.1.1.1 32-1.4.1.1 33-1.4.1.1.2.1.1 34-1.4.1
SDL-AMR-09
H2O2
-
54
Upregulation of HER3 has been found to mediate resistance to PI3K @/@ AKT ( 26 ) or HER2 ( 27 ) inhibitors in HER2 @-@ amplified breast cancer cell lines , which is caused in part through a FoxO3A @-@ dependent induction of HER3 gene transcription .
bio.bmtr_0003.3
0-1.1.1 1-1.1.1.1.r 2-1.1.1.1.1.1 5-1 6-1.1.3 7-1.1 8-1.1.2 9-1.1.2.1.r 10-1.1.2.1.1.1.1.1.1 12-1.1.2.1.1.1.1.1.1 14-1.1.2.1.1.1.1.2.1.1.1 16-1.1.2.1.1.1 17-1.1.2.1.1.1.2.1.1 19-1.1.2.1.1.1.2.2.1.1 21-1.1.2.1 21-1.1.2.1.1 21-1.1.2.1.1.r 22-1.1.2.2.r 23-1.1.2.2.1.1 25-1.1.2.2.1 26-1.1.2.2.2.2.1 27-1.1.2.2.2.2.2 28-1.1.2.2 29-1.1.2.2 33-1.1.3 34-1.1.3.2 34-1.1.3.2.r 35-1.1.3.2.r 38-1.1.3.1.2.1.1.1 40-1.1.3.1.2 41-1.1.3.1 42-1.1.3.1.1.r 43-1.1.3.1.1.1.1.1 44-1.1.3.1.1.1 45-1.1.3.1.1
SDL-AMR-09
-
Raf
1988
293T
BCR
B-Raf
axin
threonine
677
RKO
beta-catenin
117
lysine
ERK1
PLX4032
827
RalGDS
GDP
lysine
pmid_1528_0923.94
0-1.1.1.1 1-1.1 4-1.1.2.1.1 4-1.1.2.1.1.2 4-1.1.2.1.1.2.r 5-1.1.2.1.1.1.1 6-1.1.2.1 8-1.1.2.1.2.1.1 10-1.1.2.1.2.1.1 12-1 13-1.2.1.3 14-1.2.1.1 15-1.2.1 16-1.2.1.2.r 17-1.2.1.2 20-1.2.1.2.2.2 21-1.2.1 21-1.2.1.2.2 21-1.2.1.2.2.1 21-1.2.1.2.2.1.r 22-1.2 23-1.2.2.3.1 23-1.2.2.3.1.r 24-1.2.2.3 25-1.1.2.1.2.2.1 25-1.2.2 25-1.2.2.3.1 25-1.2.2.3.1.r 26-1.2.2.2.r 28-1.2.2.2 31-1.1.2.1.2.1.1 31-1.2.2.2.1.1
GI101A cells , with low EGFR and nonactivated ERK1 @/@ 2 , showed modest growth inhibition when treated with an individual inhibitor and no significant difference with the combination of the two .
SDL-AMR-09
15280923
--
0.5
MDA-MB-231
w2
IGF-IR
1
MDA-MB-435
BRAF
1995
ERK12
caspase
-42
-
A-T
ERK
ASPP2
2
PP1C
Sasaki
Erk
GATA-1
MAPK1
Erk12
CTn repeat
SPT5
p42MAPK
Mek
PKI166
1B
HER2
30
3B
flow cytometry
G76C
lamin B
N-terminus
serine
621
677
threonine
interrogative
MDA-MB-468
NF-kB
-
tyrosine
Axin
RBD
-
Breast_cancer
breast cancer
5A
Upon CTD phosphorylation by TFIIH , RNA pol II dissociates from the initiation complex and leaves the promoter .
SDL-AMR-09
bio.chicago_2015.18156
2-1.3 3-1.3.2.r 4-1.3.2.1.1 6-1.1.1.1.1 7-1.1.1.1.2 8-1.1.1.1.3 9-1.1 10-1.1.2.r 12-1.1.2.1 13-1.1.2 14-1 15-1.2 17-1.2.2 17-1.2.2.1 17-1.2.2.1.r
BRAF
GST-RBD
V600E
glycogen synthase kinase3 beta
CTD
4
EGFR
HER2
11
27
threonine
tyrosine
trypsin
e3
d11
6C
ERK12
ERK2
PKI166
ZFN217
3E
1
B-Raf
-
s2
siRNA
698
Cancer
cancer
bmtr_0006.10
0-1.1.1.1 1-1.3 2-1 3-1.2.r 4-1.2.1.1 7-1.2 7-1.2.2 7-1.2.2.r 9-1.2.2.1.1.3.1 11-1.2.2.1.1.3 12-1.2.2.1.1 12-1.2.2.1.1.1 12-1.2.2.1.1.1.r 13-1.2.2.1 14-1.2.2.1.2.r 15-1.2.2.1.2 16-1.2.2.1.1.2.r 18-1.2.2.1.1.2.2 19-1.2.2.1.1.2.2 20-1.2.2.1.1.2.1.1 22-1.2.2.2 23-1.2.2.2.1 24-1.2.2.2.1.1 25-1.2.2.2.1.1.3.r 26-1.2.2.2.1.1.3 26-1.2.2.2.1.1.3.1 26-1.2.2.2.1.1.3.1.r 28-1.2.2.2.1.1.2.r 30-1.2.2.2.1.1.2.1.1 32-1.2.2.2.1.1.2.1 33-1.2.2.2.1.1.2
SDL-AMR-09
PI3KC2β preferentially interacts with Ras17N , which has a 30 @-@ fold lower affinity for nucleotide compared to wild type Ras and therefore should exist for longer periods in the nucleotide @-@ free state .
B
G-domain
G3 box
ERBB3
SDL-AMR-09
0-1 3-1.1.1.3.1.2 4-1.1.1.3.1 4-1.1.1.3.1.1 4-1.1.1.3.1.1.r 5-1.1.1.3 6-1.1.1.3.r 8-1.1.1.2 10-1.1.1.1.1 12-1.1.1.1.1 14-1.1 15-1.1 16-1.1.2.r 18-1.1.2.1.1 20-1.1.2.1.1 22-1.1.3.1.1 24-1.1.3.1.1.1 25-1.1.3.1 26-1.1.3.1.1 26-1.1.3.1.2 27-1.1.3.1.2.1
However , a much greater fraction of the ubiquitinated @-@ K @-@ Ras was pulled down by the GST @-@ RBD ( Fig . 2C and fig. S1D ) .
bio.bmtr_0001.20
p2
ERK
2
PAF
IGF-IR
PI3KC2β
H-Ras
-
GTPase
ERK12
serine
216
-
e
H-Ras
Ras
glucose
70
1
7
Ras
E1 E-box
2000
ubiquitin
serine
PDGF
FoxO13A
p53
IL-6
Lu
6
Following purification , mono @- and di @- ubiquitinated K @-@ Ras appeared to be the major ubiquitination forms , which is consistent with the endogenous K @-@ Ras ubiquitination pattern ( Fig . 1 , A and B ) .
bio.bmtr_0001.6
SDL-AMR-09
0-1.3 1-1.3.1 3-1.1.3.1.1 3-1.1.3.1.1.r 5-1.1.3 6-1.1.3.2.1 6-1.1.3.2.1.r 8-1.1.3.1 8-1.1.3.2 9-1.1.3.1.2.1.1 11-1.1.3.1.2.1.1 12-1 14-1.1.3.r 16-1.1.2 17-1.1.1 18-1.1 21-1.1.3.r 22-1.1.4 23-1.1.4.1.r 25-1.1.4.1.1.1.2 26-1.1.4.1.1.1.1.1 28-1.1.4.1.1.1.1.1 29-1.1.4.1.1 30-1.1.4.1 32-1.2.1.1 32-1.2.1.2 34-1.1.3.1.1 37-1.2.1
ERBB3
30
RKO-E1
10
8
JM domain
ROK
2
13
Spt
GAP
1
3
T669A
p
2
1
Raf
0-1.2.1.1.1 1-1.2 2-1 3-1.1 3-1.1.r 4-1.3 5-1.3.1.r 6-1.3.1.2 7-1.3.1.1.1.1 8-1.3.1 10-1.4 11-1.4.1.r 13-1.4.1.3.2 14-1.4.1.3.1.1.1 15-1.4.1.3 17-1.4.1.1 17-1.4.1.1.r 18-1.4.1 19-1.4.1 20-1.4.1.2.1 21-1.4.1.2
SDL-AMR-09
Hemin treatment caused no reduction in cellular glutathione concentrations , indicating that the increased TRX expression was not due to oxidative stress .
bio.chicago_2015.18130
B-Raf
4
Grb2
s
HER3
e
2E
B-Raf
Ras
37
36
Programmed cell death is a key feature of proliferation control in homeostasis and overcoming apoptosis is considered another hallmark of cancer cells [ @<xref ref-type="bibr" rid="B28"> 28 </xref>@ ] .
0-1.1.1.1.2 1-1.1.1.1.1 2-1.1.1.1 5-1.1.1 6-1.1 7-1.1.2.r 8-1.1.2.1 9-1.1.2 10-1.1.3.r 11-1.1.3 12-1 13-1.2.1.2 14-1.2.1.2.1 15-1.2.1.2.r 16-1.2 17-1.2.1.3 18-1.2.1 19-1.2.1.1.r 20-1.2.1.1.1.2.1 21-1.2.1.1 24-1.2.2.1.1.1
a_pmid_2488_5690.65
SDL-AMR-09
24885690
5.0
HER2
U1026
Ras
B-Raf
EGFR
ERK2
In contrast , somatic cell gene targeting enables quantitative knockouts of single alleles ( Figure <xref ref-type="fig" rid="F1"> 1 </xref>@ A ) and the generation of endogenous models featuring well @-@ defined genetic backgrounds [ @<xref ref-type="bibr" rid="B18"> 18 </xref>@ ] .
a_pmid_2488_5690.36
24885690
1-1 3-1.1.1.1.1.1 4-1.1.1.1.1 5-1.1.1.1 5-1.1.2.2.1.2.1.1 6-1.1.1 7-1.1 8-1.1.2.1.2 9-1.1.2.1 10-1.1.2.1.1.r 11-1.1.2.1.1.1 12-1.1.2.1.1 14-1.1.2.1.3.1 20-1.1.2 22-1.1.2.2 23-1.1.2.2.1.r 24-1.1.2.2.1.1 25-1.1.2.2.1 26-1.1.2.2.1.2 27-1.1.2.2.1.2.1.2.1 29-1.1.2.2.1.2.1.2 31-1.1.2.2.1.2.1 34-1.2.1.1.1
SDL-AMR-09
lamin B
p3
3D
EGFR
147
lysine
1D
445
serine
STAT
beta-catenin
2D
Tolloid
dup7q21q36
tyrosine
ERK12
42
B-Raf
threonine
p2
2-1.1.1.2 3-1.1.1 3-1.1.1.1 3-1.1.1.1.r 4-1.1 5-1.1.2.r 6-1.1.2.1.1.2 7-1.1.2.1.1.1.1 8-1.1.2.1.1 8-1.1.2.2.2.1.1.1 8-1.1.2.2.2.2.1.1 9-1.1.2.1 10-1.1.2.1.2.r 12-1.1.2.1.2.1.1 13-1.1.2.1.2.1.2 15-1.1.2.1.2.1.2 16-1.1.2 18-1.1.2.2 19-1.1.2.2.2.1.1.1.1.1 21-1.1.2.2.2.1.1.1.1.1 22-1.1.2.2.2.1 22-1.1.2.2.2.1.1 22-1.1.2.2.2.1.1.r 23-1.1.2.2.2 26-1.1.2.2.2 29-1.1.2.2.2.2 30-1.1.2.2.2.2.1.r 32-1.1.2.2.2.2.1 34-1.1.2.2.2.2.1.1.1.1
SDL-AMR-09
Thus , these results suggest that endogenous bHLH proteins bind to the E1 E @-@ box and consequently activate GAP @-@ 43 promoter activity , an activity that is affected by the action of Id2 .
bio.chicago_2015.18079
e
Par6b
lysine
147
dabrafenib
ASPP2
ASPP2
serine
750
2
beta-catenin
AMR-PropBank-Role
4
MDA-MB-435
63
e2
p3
0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 3-1 4-1.2.r 6-1.2 9-1.2.1.1 13-1.2.1.1.1 17-1.2.1 18-1.2.1.2.1.1.1 19-1.2.1.2 21-1.2.1.3 22-1.2.1.3.1.3 23-1.2.1.3.1.1 25-1.2.1.3.1.2.1.1 26-1.2.1.3.1
These results are consistent with a model in which ubiquitination of Lys147 ( or Lys117 ) , destabilizes GDP binding , allowing spontaneous GDP @/@ GTP exchange .
SDL-AMR-09
bio.bmtr_0001.13
BRAF
SUM149
p19INK4D
0-1.1.1 1-1.1 2-1.1.2.1 4-1 5-1.2.r 6-1.2.1.1.1 8-1.2.1.1.1 9-1.2 10-1.2.2 11-1.2.2.1.r 12-1.2.2.1.1.1.1 12-1.2.2.1.1.1.2 13-1.2.2.1 16-1.2.2.2.1.1 17-1.2.2.2 20-1.2.2.2.2 21-1.2.2.2.2.1 23-1.2.1 23-1.2.2.2.2.1.1 25-1.2.2.2.2.1.1 26-1.2.2.2.2.1.1 27-1.2.2.2.2.1.1.1.1 29-1.3.1.1.1.1 31-1.3.1.1.1.2
bel_pmid_1088_0513.23686
We and others have shown that IL @-@ 6 induces growth in MM cells via the MAPK pathway , which includes activation of protein @-@ tyrosine phosphatase SHP2 ( 16 , 28 )
SDL-AMR-09
10880513
GTP
K46^mA
EGFR
-
-
5
EGFR
Pin1
B-Raf
Shimell
S1D
Raf
Myc
Axin
2A
CCT
C-Raf
dpc
ERK
beta-cateninTcf
Id2
cytokine
threonine
EGFR
NGH.S4
GDP
Ras
Ras
EGFR
8
vemurafenib
5
G box
SDL-AMR-09
bel_pmid_1074_4722.21168
10744722
Both Chk1 and Chk2 @/@ Cds1 have been shown to localize to the nucleus and to phosphorylate serine 216 of Cdc25C in vitro ( 13 , 15 ) ( 18 @–@ 21 ) .
1-1.1.1.1.1.1.1 3-1.1.1.1.2.1.1.1 5-1.1.1.1.2.2.1.1 7-1.1.1 8-1 10-1.1.1 13-1.1.1.2 14-1.1 16-1.1.2 17-1.1.2.1.2.1 18-1.1.2.1.1 20-1.1.2.1.3.1.1 21-1.1.2.3 22-1.1.2.3 24-1.2.1.1.1.1.1 26-1.2.1.1.1.1.2 29-1.2.1.2.1.1.1 31-1.2.1.2.1.1.2
p
STAT3
EGFR
8
SDL-AMR-09
Ras acts as a molecular switch that is activated upon GTP loading and deactivated upon hydrolysis of GTP to GDP .
0-1.1.1.1 4-1.4 5-1 7-1.1.r 8-1.2 10-1.2.1.2.1.1 11-1.2.1 13-1.3 15-1.3.1 16-1.3.1.1.r 17-1.3.1.1 18-1.3.1.2.r 19-1.3.1.2.1.1
bio.ras_0001.3
phosphoinositide 3-kinase AKT
Groucho
1
oxaliplatin
EGFR
Michaloglou
BRAF
actin
EGFR
We found that TPO stimulation or Ha @-@ Ras G12V expression led to up @-@ regulation of cyclin D1 , cyclin D2 , and cyclin D3 expression .
SDL-AMR-09
0-1.1 1-1 2-1.2.r 3-1.2.1.1.1.1.1 4-1.2.1.1 5-1.2.1 6-1.2.1.2.1.1.1 8-1.2.1.2.1.1.1 9-1.2.1.2.1.2.1 10-1.2.1.2 11-1.2 12-1.2.2.r 13-1.2.2 14-1.2.2 15-1.2.2 16-1.2.2.1.r 17-1.2.2.1.1.1.1.1 18-1.2.2.1.1.1.1.2 20-1.2.2.1.2.1.1.1 21-1.2.2.1.2.1.1.2 23-1.2.2.1 24-1.2.2.1.3.1.1.1 25-1.2.2.1.3.1.1.2 26-1.2.2.1.1 26-1.2.2.1.2 26-1.2.2.1.3
bel_pmid_1068_1535.5746
10681535
B-Raf
89
C-terminus
Raf
A
4
EGFR
1990
-
4
K-Ras
S5A
8
K-Ras
SDL-AMR-09
The minimal HER3 promoter region regulated by MAPK inhibitors overlaps with sequences previously described to be immunoprecipitated using antibodies against the ZFN217 transcription factor and CtBP1 @/@ CtBP2 corepressors ( 28 @–@ 30 ) .
bio-exp_0001.10
1-1.1.1.2 2-1.1.1.1.1.1.1 3-1.1.1 3-1.1.1.1 3-1.1.1.1.r 4-1.1 5-1.1.2 6-1.1.2.1.r 7-1.1.2.1.1.1.1.1 8-1.1.2.1 8-1.1.2.1.1 8-1.1.2.1.1.r 9-1 10-1.2.r 11-1.2 12-1.2.1.2.1 13-1.2.1.2 13-1.3 16-1.2.1 17-1.2.1.1 18-1.2.1.1.1 19-1.2.1.1.1.1 21-1.2.1.1.1.1.1.1.1.1.1.1 22-1.2.1.1.1.1.1.1.1 23-1.2.1.1.1.1.1.1 24-1.2.1.1.1.1.1 25-1.2.1.1.1.1.1.2.1.1.1.1.1 27-1.2.1.1.1.1.1.2.1.1.2.1.1 30-1.3.1.1.1.1 32-1.3.1.1.1.2
C-Raf
63
PKI166
p4
81
threonine
669
PBS
-
BCR
JM domain
actin
U0126
MDA-MB-435
tyrosine
Ras
Silencing of CtBP1 , and to a lesser extent CtBP2 , increased basal HER3 in 8505C cells , and markedly potentiated the effects of PLX4032 ( Fig. 5D and 5E ) .
bio-exp_0001.12
0-1.1.1 1-1.1.1.1.r 2-1.1.1.1.1.1.1 4-1.1.1.1 7-1.1.1.1.2.2 7-1.1.1.1.2.2.1 7-1.1.1.1.2.2.1.r 9-1.1.1.1.2.1.1 11-1.1 12-1.1.2.2 13-1.1.2.1.1 14-1.1.3.r 15-1.1.3.1.1 16-1.1.3 18-1 18-1.3.1 19-1.2.3 22-1.2.1 23-1.2.1.1.r 24-1.2.1.1.1.1 26-1.3.1.1 26-1.3.1.2 27-1.3.1.1.1 28-1.3.1 29-1.3.1.2.1
SDL-AMR-09
C-terminus
PKI166
serine
B-Raf
HEK293T
IL-11
10
GTP
5E
Ldb
breast cancer
Breast_cancer
Raf
thioredoxin
B-Raf
-
76
Saos2
B-Raf
Dl
PAFR transcript 1
C-Raf
ICAT
0-1.3 1-1.3.2.1 2-1.3.2 4-1.1.1 6-1.1 8-1.1.2.1.1 8-1.2.2.2.1.2.1.1 10-1.1.2 11-1.1.3.r 13-1.1.3.2.2.1 14-1.1.3.2.2.2 15-1.1.3 16-1.1.3 17-1.1.3.1.1 18-1 19-1.2 20-1.2.2.1 21-1.2.2 23-1.2.2.2 25-1.2.2.2.1.1.3 27-1.2.2.2.1.1.1.1 29-1.2.2.2.1.1 29-1.2.2.2.1.2 32-1.2.2.2.1.1.2 34-1.2.2.2.1.1.2 35-1.2.2.2.1 36-1.2.2.2.1.2.2
Utilizing this method , we have disrupted <i> BRAF </i> alleles in the colorectal cancer cell line RKO and established syngeneic clones which harbor a single <i> BRAF </i> allele of either wild @-@ type or mutant genotype .
24885690
SDL-AMR-09
a_pmid_2488_5690.37
CHO-KI
Jak3
365
serine
C-RAF
BCR
SHP2
Ras
PLD
-
brinker
7A
1
HER3
750
serine
-
green fluorescence protein
RBW-1
ERK
ITIM
EGFR
-
-
SH3PX1
threonine
401
C-terminus
G466A
1A
RA
PI3KAKT
10699758
Additionally , several studies have shown that antioxidant enzymes and mimics also block NF @-@ kB activation by various stimuli . For example , overexpression of peroxiredoxin [ 247 ] or thioredoxin [ 111 ] blocks NF @-@ kB activation by H2O2 .
bel_pmid_1069_9758.24188
0-1.1.3 2-1.1.1.1 3-1.1.1 5-1.1 6-1.1.2.r 7-1.1.2.1.1.1 8-1.1.2.1.1 9-1.1.2.1 10-1.1.2.1.2 11-1.1.2.4 12-1.1.2 13-1.1.2.2.1.1.1 15-1.1.2.2.1.1.1 16-1.1.2.2 17-1.1.2.3.r 18-1.1.2.3.1 19-1.1.2.3 21-1.2.4 22-1.2.4 24-1.2.1.1 24-1.2.1.2 25-1.2.1.1.1.r 26-1.2.1.1.1.1.1 28-1.2.1.1.2.1.1.1 30-1.2.1 31-1.2.1.2.1.1.1 33-1.2.1.2.2.1.1.1 35-1.2 36-1.2.2.1.1.1 38-1.2.2.1.1.1 39-1.2.2 40-1.2.3.r 41-1.2.3.1.1
SDL-AMR-09
threonine
753
30
C-Raf
60
1
c
cyclin D1
PLD
SDL-AMR-09
15280923
pmid_1528_0923.108
0-1.1.1.1.1 1-1.1 2-1.1.2.1.1.1 4-1.1.2.1.1.1 5-1.1.2 6-1.1.3.r 7-1.1.3.1.1 8-1.1.3 10-1.2.1.2.r 12-1.1.4.1.1.1 13-1.1.4.1.2 15-1 16-1.2.1.2 17-1.2.1 18-1.2.1.1.r 20-1.2.1.1 21-1.2.1.1.1.r 22-1.2.1.1.1 24-1.2.2
PKI166 inhibited ERK1 @/@ 2 phosphorylation in SUM149 cells , as did U0126 alone , and further inhibition by the combination of drugs was barely discernible .
26
threonine
PS1
ERK12
Ras
beta-catenin
1B
C-Raf
p44ERK1
k
8
GTP
Ras
p2
C-Raf
cdc5 delta N
Ras
Notch
34
ASPP2
K-Ras
C-Raf
CtBP1
a
PKI166
1994
Ras
paclitaxel
S729A
C-Raf
C-Raf
actin
-401
90
Mlodzik
2
SUM149
DNA
DNA
CtBP
cyclin E
p3
p2
GSK-3beta
APC
B-Raf
bHLH
HRASV12
19
GTP
ERK
DLT
1B
6B
G-domain
GTP
3D
Lef-1
interrogative
cdk4
GAP
JM domain
M1
JAK2
carcinoma
PMSF
CD72
B-Raf
c
5
ERK
729
serine
GTP
Mac-1
GAP
SDL-AMR-09
24885690
a_pmid_2488_5690.41
Subsequently , either wild @-@ type or V600E @-@ mutant B @-@ Raf was disrupted by targeting a second allele in RBOW , yielding six <i> BRAF </i>@ -@ mutant and one wild @-@ type clone from approximately 10 @<sup> 4 </sup> screened colonies .
0-1.4 0-1.4.r 3-1.1.1.2 5-1.1.1.2 6-1.1 7-1.1.2.2.1 9-1.1.2 9-1.1.2.2 9-1.1.2.2.r 10-1.1.1.1.1 10-1.1.2.1.1 12-1.1.1.1.1 12-1.1.2.1.1 14-1 15-1.2.r 16-1.2 18-1.2.1.2 18-1.2.1.2.1 18-1.2.1.2.1.r 19-1.2.1 20-1.2.1.1.r 21-1.2.1.1.1.1 23-1.3 24-1.3.1.1.1 26-1.3.1.1.2.1.1.1 29-1.3.1.1.2 30-1.3.1 31-1.3.1.2.1 32-1.3.1.2.2 33-1.3.1.2.2 34-1.3.1.2.2 35-1.3.1.1 35-1.3.1.2 36-1.3.2.r 37-1.3.2.2 42-1.3.2.1 43-1.3.2
AZD6244
SDL-AMR-09
1-1.6 2-1.6.2.r 4-1.6.2.2 7-1.5.1 7-1.5.1.1.3 7-1.6.2.2.1 7-1.6.2.2.1.3.1 7-1.6.2.2.2 9-1.6.2.2.2.1.1 10-1.6.2.2.1.3 10-1.6.2.2.2.1 13-1.6.2.2.1.1.1 14-1.6.2.2.1.1 16-1.6.2.2.2.2.1 17-1.6.2.2.2.2 22-1.6.2.1 22-1.6.2.1.r 23-1.6.2 24-1.6.2.3.1.1.1 28-1.1 29-1 31-1.2.2 32-1.2.1.1 32-1.4.2.2.1 37-1.3.1.1 39-1.3.2.1.1 41-1.3.2.1.1 46-1.4.r 47-1.5 50-1.5.1.1.1.1 51-1.5.1.1.1 52-1.5.1.1 52-1.5.1.1.2 52-1.5.1.1.2.r 53-1.5.1.1.3.r 55-1.5.1.1.3.1
To verify that the differences between the enzymatic and chemical ubiquitination linkers ( seven bonds and five bonds , respectively ) do not alter GAP @-@ responsiveness , we placed an additional cysteine at the c @-@ terminus of Ubiquitin ( Ubiquitin @-@ C77 ) , thereby creating a linker one bond longer than the native linker .
bio.bmtr_0004.9
SUM149
GTP
calponin
0-1 0-1.1 0-1.1.r 2-1.1.1.1.1 2-1.1.1.1.1.1 2-1.1.1.1.1.1.r 3-1.1.1.1 4-1.1.1 5-1.1.1.2.r 6-1.1.1.2.2.1.1 7-1.1.1.2 8-1.1.1.3.r 9-1.1.1.3.2 10-1.1.1.3 12-1.1.2 14-1.1.2.1.4 15-1.1.2.1.4.2 16-1.1.2.1.4.1 18-1.1.2.1.1 18-1.1.2.1.1.r 19-1.1.2.1 20-1.1.2.1.3.1.2.1 21-1.1.2.1.3 22-1.1.2 23-1.1.2.2 24-1.1.2.2.2
10851026
SDL-AMR-09
bel_pmid_1085_1026.8692
However , immature osteoblasts respond to FGF treatment with increased proliferation , whereas in differentiating cells FGF does not induce DNA synthesis but causes apoptosis .
p44MAPK
Cancer
cancer
-
ASPP2
T669A
However , not all of the high EGFR @-@ expressing lines were sensitive to PKI166 .
SDL-AMR-09
pmid_1528_0923.85
15280923
0-1 2-1.1.1.2.1 2-1.1.1.2.1.r 3-1.1.1.2 6-1.1.1.1.2 7-1.1.1.1.1.1.1 9-1.1.1.1 10-1.1.1 12-1.1 13-1.1.2.r 14-1.1.2.1.1
p7
BRAF
2C
Pin1
6A
SDL-AMR-09
0-1 1-1.1.r 2-1.1.1.1 6-1.2.1 9-1.2.2.1 9-1.2.2.1.1 9-1.2.2.1.1.r 10-1.2.2 11-1.2 12-1.2.3 13-1.2.3.1.1.1 14-1.2.3.1.1 16-1.2.3.1.2.1 16-1.2.3.1.3.1 17-1.2.3.1.2 19-1.2.3.1.3 21-1.2.3.1 23-1.2.3.1.4.2 25-1.2.3.1.4.1 26-1.2.3.1.4 32-1.2.3.1.4.3.1.1 32-1.2.3.1.4.3.1.1.1 34-1.2.3.1.4.3.1.1.1.r 36-1.2.3.1.4.3.1.1 36-1.2.3.1.4.3.1.1.1 37-1.2.3.1.4.3.1 38-1.2.3.1.4.3.1.2 39-1.2.3.1.4.3.1.2.1.1.1 40-1.2.3.1.4.3.1.2.1.1.2 41-1.2.3.1.4.3.1.2.1.1 42-1.2.3.1.4.3.1.2.1 44-1.1.1.1 45-1.2.3.1.4.3.1.2.1.2 47-1.2.3.1.4.3.1.2.1.2.2.1.1.1 48-1.2.3.1.4.3.1.2.1.2.1 48-1.2.3.1.4.3.1.2.1.2.2
bio-kappa_0001.1
Activation of Raf occurs via a complex , yet incompletely understood mechanism requiring membrane translocation , regulatory phosphorylation / dephosphorylation events and , crucially , allosteric activation in the context of a side @-@ to @-@ side dimer comprising two Raf molecules or a Raf and a Ksr molecule .
actinin
1A
4B
MAPK
NURF
MAPK
Dvl
HER3
12
253
De Cesare
Sos
0-1.1.1.1 3-1.3 6-1.2.1.1.1 6-1.2.2.1.1 8-1.2.1.1.1 10-1.2.1.1.1 10-1.2.2.1.1 12-1.2.2.1.1 14-1.2.3.1.1 14-1.2.4.1.1 16-1.2.3.1.1 18-1.2 19-1.2.4.1.1 21-1.2.3.1.1 21-1.2.4.1.1
Sorafenib is a potent TKI of VEGFR @-@ 2 , VEGFR @-@ 3 , B @-@ RAF , and PDGFR @-@ B
SDL-AMR-09
bio.bel_0002.9
fcp1
-
-
1
MEK
interrogative
EGFR
serine
43
BRAF
669
threonine
guanine nucleotide-binding
Mammalia
p27KIP1
-
catenin
p
guanine nucleotide exchange factor
MAPK
-
Ras
47
MEK
neurotrophin
Iro-C
bel_pmid_1064_0734.39814
10640734
0-1.3 2-1.1.2 3-1.1.2 4-1.1.1 5-1.1 6-1 7-1.2.r 9-1.2.1 9-1.2.3 10-1.2.1.1.r 11-1.2.1.1.1.1 12-1.1.2 15-1.2.1.2.1.2 16-1.2.1.2.1.1.1 17-1.2.1.2.2.1.1.1 18-1.2.1.2 18-1.2.1.2.2 18-1.2.1.2.2.r 20-1.2 20-1.2.2 20-1.2.2.r 21-1.2.3.r 26-1.2.3.1 27-1.2.3.1 29-1.4.1 31-1.4.1.1
SDL-AMR-09
Indeed , in vitro kinase assay showed that the activity of ERK2 in Ag @-@ stimulated K46^mA CD72 transfectants was lower than that of Ag @-@ stimulated K46^mA ( Fig . 3 ) .
filamin
bio.chicago_2015.18675
SDL-AMR-09
Unlike known E2Fs , these E2F @-@ like proteins efficiently bind E2F sites in the monomeric form but not as a heterodimer with DP proteins and repress E2F @-@ regulated promoters .
0-1.1.1.2 0-1.1.1.2.1 0-1.1.1.2.1.r 1-1.1.1.2.2 1-1.1.1.2.2.2 1-1.1.1.2.2.2.r 4-1.1.1.3 5-1.1.1.1.1.1.1 5-1.1.1.2.2.1.1 7-1.1.1.1 7-1.1.1.2 8-1.1.1 9-1.1.3 10-1.1 11-1.1.1.1.1.1.1 11-1.1.1.2.2.1.1 12-1.1.2 16-1.1.4.1 17-1.1.4 18-1.1.4.2.1 18-1.1.4.2.1.r 21-1.1.4.2 22-1.1.4.2.2.r 23-1.1.4.2.2.1.1 24-1.1.1 25-1 26-1.2 27-1.2.1 29-1.2.2.2 30-1.2.2 30-1.2.2.1 30-1.2.2.1.r
GTP
ASPP2
Cdc5
Ras
To test whether endogenous ASPP2 could be phosphorylated in cells , Saos2 cells were grown in low serum for 50 hours to remove all background stimulation of RAS , after which the cells were stimulated with EGF and 20 % fetal calf serum ( FCS ) .
SDL-AMR-09
bmtr_0007.7
1-1.5 2-1.5.1.1 2-1.5.1.1.r 3-1.5.1.2.1.2 4-1.5.1.2.1.1.1 5-1.5.1 7-1.5.1.2 8-1.5.1.2.2.r 9-1.5.1.2.2 11-1.1.1.1 12-1.1 14-1 15-1.2.r 16-1.2.1 17-1.2 18-1.3.r 19-1.3.1 20-1.3.2 22-1.4 23-1.4.1.3 24-1.4.1.2 25-1.4.1 26-1.4.1.1.r 27-1.4.1.1.1.1 29-1.6 32-1.6.1.1 34-1.6.1 35-1.6.1.2.r 36-1.6.1.2.1.1.1 37-1.6.1.2 38-1.6.1.2.2.2.1 39-1.6.1.2.2.2 40-1.6.1.2.2.1 41-1.6.1.2.2.1.1 42-1.6.1.2.2
2A
TPO
6
HER2
threonine
-
cyclin D1
urea
Yamazaki
cyclin D1
ASPP2
0-1.3 2-1.1.2 3-1.1 3-1.1.1 3-1.1.1.r 4-1 6-1.2 9-1.2.1 12-1.2.1.1.1 14-1.2.1.1.1.1.r 16-1.2.1.1.1.1.1.2 17-1.2.1.1.1.1 18-1.2.1.1.1.1.2.2 19-1.2.1.1.1.1.1 19-1.2.1.1.1.1.1.3 19-1.2.1.1.1.1.1.3.1.2.1 19-1.2.1.1.1.1.1.3.r 20-1.2.1.1.1.1.1.1.1 20-1.2.1.1.1.1.2.1.1 22-1.2.1.1.1.1.1.1.1 22-1.2.1.1.1.1.2.1.1 24-1.2.1.1.1.1 25-1.2.2.1 25-1.2.2.1.r 26-1.2.2 27-1.2.2.2.r 28-1.2.2.2.1 29-1.2.2.2 30-1.2.2.2.2 31-1.2.2.2.1.2.1.1 33-1.2.2.2.1.2.1.1
Together , these findings indicate a correlation between the changes in the transformation potentials of the intermediate and impaired oncogenic B @-@ Raf proteins and their abilities to heterodimerize and activate C @-@ Raf .
SDL-AMR-09
bio.mskcc_0001.37
K-Ras
EGFR
21
Shaw
PI3KAKT
ERK
bio.bmtr_0003.5
Similar results were found following treatment with the MEK inhibitor AZD6244 ( not shown ) .
0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 3-1 4-1.2 5-1.2.1 6-1.2.1.1.r 8-1.2.1.1.2.1.1.1 9-1.2.1.1 9-1.2.1.1.2 9-1.2.1.1.2.r 10-1.2.1.1.1.1 12-1.2.1.1.3.1 12-1.2.1.1.3.1.r 13-1.2.1.1.3
SDL-AMR-09
EGFR
T753A
ERK
ATP
1E
-
4
Ras
e
SDL-AMR-09
0-1.1.1 3-1.1.2.1.1 5-1.1.2.1.1 6-1.1 8-1.1.3 10-1.1.3.1.1.1 12-1.1.3.1.1.1 14-1.1.3.2.1.1 17-1.1.4 19-1.1.4.1.1 20-1.1.4.1 22-1.1.4.1.2 23-1.1.4.1.2.1.r 25-1.1.4.1.2.1.1 26-1.1.4.1.2.1 28-1.2.1 31-1.2.2 32-1.2.2 33-1.2.2 34-1.2 36-1.2.3 37-1.2.3.1.r 38-1.2.3.1.1.1 42-1.1.3.1.1.1 44-1.1.1 44-1.1.3.1.1.1 45-1.2.3.2 47-1.2.4 48-1.2.4.1.1 49-1.2.4.1 50-1.2.4.1.2.r 51-1.2.4.1.2 53-1 54-1.3.1 57-1.3.2 58-1.3.2 59-1.3.2 60-1.3 62-1.3.3.1 63-1.3.3 66-1.1.3.2.1.1 68-1.2.3.1.1.1 69-1.3.4.1 69-1.3.4.2 70-1.3.4 71-1.3.4.1.1 72-1.3.4.1.1 73-1.3.4.1.1 74-1.3.4.1 75-1.3.5.r 77-1.3.5 78-1.3.5.1.r 79-1.3.5.1.1.1 80-1.3.5.1.1 81-1.3.5.1 86-1.3.6.1.3 87-1.3.6.1 89-1.3.6.1.2.1 90-1.3.6.1.2.2 91-1.3.6.1.2
1 ) the MLC @-@ pep blocks an interaction between vMLC @-@ 1 and actin , which releases a tethering effect that leads to the inotropic effect ; 2 ) the MLC @-@ pep blocks a site on myosin to which the vMLC @-@ 1 binds that disrupts myosin binding to actin ; and 3 ) the MLC @-@ pep exerts a direct effect on the actin @-@ myosin interaction or actin @-@ actin interactions in the presence of regulatory proteins and Ca2+, such that it cooperatively stimulates the entire thin filament .
bio.chicago_2015.19248
FoxO3A
-
Hulsken
1B
669
threonine
BRAF
Colorectal_cancer
colon cancer
-
33
C-Raf
2
-
CBP
VEGFR-3
Ramos human lymphoblastoid
MEK
PI3KC2β
MDA-MB-468
alphaFtz-F1
1999
Montero-Conde
ERK
293T
K-Ras
eosinophil
14-3-3
PKC betaII
R4 precursor
bcl-xL
MEK
RASRafMAPK
A
EGFR
1
5D
Cancer
cancer
30
Sos
PMC3441633
p53
PA
N-terminus
K-Ras
FACS
PAF
Ftz
EGF
5D
RNA
Arp1
PKA
GFP
gp130
448
Cancer
cancer
750
serine
B-Raf
-
Phosphatidylinositol 3-Kinase Beta
C-Raf
151
serine
2B
MEKERK
GDP
Cdc11
RAS
1C
PP2A
PUMA
ASPP2
ATM
cyclin D2
B
MDA-MB-435
2B
ZFN217
E1A
SKBR3
0-1.4.1.1.1.r 1-1.4 2-1.4.1 4-1.4.1.1.1 5-1.4.1.1 7-1.1.1.2 9-1.1.1.2 10-1.1.1.1.1 12-1.1.1.1.1 13-1.1 14-1.1.3 15-1.1.2.2 15-1.1.2.2.1.1 17-1.1.2.1.1 19-1 20-1.2.1.2.1 22-1.2.1.1.1 23-1.2 24-1.2.2.2 24-1.2.2.2.1.1 26-1.2.2.1.1 31-1.3.1
bio.bmtr_0001.11
SDL-AMR-09
As expected based on previous studies , wild @-@ type K @-@ Ras bound primarily 32P @-@ GDP , while G12V @-@ Ras bound 32P @-@ GTP ( Fig.2 , A and B ) .
Cds1
5A
K-Ras
27
19
Myc
AZD6244
B-Raf
677
threonine
GTP
p34Cdc2clb
PKC
GEF
MEKK1
ASPP2
HER2
Jou
ERK
BRAF
1A
8.5
TCF
C-Raf
Ksr
Axin
U0126
50
B56alpha
PKI166
STAT3
Protein phosphatase 5
-
tyrosine
-401
PP2A
Ha-Ras
6A
S1
Ras
EGFR
Ras
B-Raf
155
RAS
FBS
gamma-secretase
Cdk2
C-Raf
NF1
60
ERK
Cancer
cancer
5D
p2
growth hormone receptor
NF-kB
w
STAT
c2
RT
14-3-3
147
lysine
32
w
1
e
-
HER3
GTP
histidine
Ras
Mek
e4
p120GAP
caspase 3
GAP
CD72
EGFR
EGFR
fascin
a-tocopherol
SUM149
GFP
Ras
PKI166
3.3
GFAP
C-Raf
S750A
PP2A
5
GDP
microtubule-associated protein 2
ERK
EGFR
GSK-3beta
Erk12
Bcl2
Ras
cyclin D3
MAPK
Raf
BRAF
Lef-1
5b
tyrosine
Ras
tyrosine
GDP
ERK12
-
Nagafuchi
RKO
RafMekErk
B-Raf
AZD6244
CTBP1
BCR
Raf
p19INK4D
GTP
0.001
JAK2
Raf-1
GSK-3beta
1B
Flag
brk
d2
B
B-Raf
ERK12
Ras
20
CtBP1
RKO
Cancer
cancer
STAT5
serine
guanosine triphosphatase
13
Flag
3F
1D
C-Raf
cadherin
Ras
ERK2
BCR
32
-
B-Raf
cetuximab
HER3
dabrafenib
GDP
Guanosine_diphosphate
MEK
p3
PKI166
SRC-1
Gem
PKI166
FRS2
HER3
focal adhesion kinase
0.5
6A
RKO
imperative
MKK1
alkaline phosphatase
MEK
p53
2A
aspartate
2
HER2
K-Ras
B-RAF
GAP
PAFR
I
cdc25C
1
AMR-PropBank-Frame
1
ISWI
2
B-Raf
K-Ras
auxilin
Raf
PLX4032
diacylglycerol
SHP2
Ral
multiple myeloma
d
PKC
1
reverse tetracycline controlled transactivator
Dpp
RBO-1
Gln61
MDA-MB-468
RAF_kinase
Raf
T669A
GTPase Activating Protein
hKSR-2
Mek12
Raf
ERK
Pol II
ERBB3
Cancer
cancer
FGF
7
ERK
6A
10
1
actin
Ha-Ras
GI101A
BRAF
HER3
G1 phase
p5
B-Raf
S729A
colorectal cancer
Colorectal_cancer
1999
DNA
2A
C-Raf
RBW-1
actin
LEF TCF
CtBP1
p5
1D
GTP
1A
c
14-3-3
EGF
-
HER3
Chk2
pTopflash plasmid
55
HER3
G466A
e2
Hsc70
tetratricopeptide domain
PKI166
Pol II
Raf
TcfLEF
GSK
AKT
HER2
PKC
B
PI3KC2β
B-Raf
V600E
EGFR
B-Raf
GDP
CtBP2
serine
216
CD72
Pin1
T401A
JAK
p53
i
Rimm
beta-catenin
cadherin
72
K-Ras
phenylmethylsulfonyl fluoride
GSK-3beta
TPO
C-Raf
C-Raf
E2F
PC
ERBB3
GSK3beta
e2
ERK12
-
GAP
DMEM
f
1995
DPP
mitomycin C
HER3
p2
GTP
1
293T
Hox
AZD6244
5B
B-Raf
200
30
H-Ras
3
serine
BCR
DNA
DNA DNA
B-Raf
1996
PMID15280923
MKK2
TM
ILK
5E
ATM
ERK
glutathione
Rheb
ASPP2
Axin
NIH 3T3
H-DNA
CtBP1
2
8
2000
Frodin
B-Raf
MEK
Murre
MAPK
GEF
HER3
p
alpha-tubulin
GFAP
Rap1
CtBP2
Ras
PKI166
GAP
HER2
K-Ras
HER3
14-3-3
14-3-3_protein
peroxiredoxin
ASPP1
Zwartkruis
Ras
cyclin D1
ASPP2
Ras
zinc finger
4A
okadaic acid
PKI166
Cancer
cancer
VEGFR-2
CD72
7B
EGFR
tyrosine
a2
ERK
1
Iro-C
e3
ASPP2
GAGA factor
ASPP
D347A
HER2
1C
microsattelite instability
ERK1
MDA-MB-468
CKI
interrogative
trypsin
ERBB3
MLC-pep
SKBR3
5c
1
GAP
PLX4032
adenomatous polyposis coli
MDA-MB-231
histidine
14-3-3
EGFR
HER3
LIM B
serine
750
EC
cyclin D1
NF1
luciferase
5b
Ftz
3
serine
MAPK
IL-6
10
9
PIK3CA
PP2A
PP2A
threonine
753
BCR
1
HER2
MAP2
-
beta-tubulin
14-3-3