bio-kappa_0001.21
Activation requires dissociation of protein - bound GDP , an intrinsically slow process that is accelerated by guanine nucleotide '96 exchange factors ( GEFs ) .
2015-01-20T08:10:38
-
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).
10744722
2015-04-14T09:31:17
bel_pmid_1074_4722.88
DSmurf
32
CK2
ERK
26
GI101A
bel_pmid_1074_7872.21238
10747872
2015-04-14T14:54:49
STAT3, but not STAT5, was activated in response to IGF-I in 293T cells cotransfected with IGF-IR and STAT expression vectors.
2015-01-06T02:02:31
bio.bmtr_0004.21
Surprisingly, monoubiquitination did not alter the intrinsic activity of Ras, despite the size of the modification.
2014-11-16T17:31:43
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.
bio.mskcc_0001.15
bio.ras_0001.6
2014-08-13T16:59:02
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 ) .
27
MEK1
MAP2K1
B-Raf
D594G
2015-10-27T05:36:13
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.
Axin
Cdc25C
2015-01-19T02:56:52
His - ubiquitinated proteins were purified by Co2+ metal affinity chromatography in 8M urea denaturing conditions .
bio.ras_0003.3
threonine
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.
2015-10-21T09:20:17
bio.chicago_2015.18163
ERK1
Erk
26
bio.bel_0002.12
2015-02-05T12:05:33
In contrast, hKSR-2 up-regulated the Rafmediated MEK activation by up to 70%.
ERBB3PI3KAKT
45
4
20
0.5
H-Ras
2
aspartate
H-Ras
Ral
B
Iro-C
2015-01-20T03:20:23
bio-kappa_0001.9
PSPs dephosphorylate phosphoserine and phosphothreonine residues .
ERK12
-
C-Raf
15280923
pmid_1528_0923.97
Treating the MDA-MB-231 cells with U0126 alone produced 8.5% inhibition, which was not significantly different from control values.
2015-06-15T14:09:53
2015-01-07T05:39:33
bio.bmtr_0005.21
Until now, it has been unclear how RAS could affect ASPP2 to enhance p53 function.
GAP
VSMC
5c
Arp1
E2F
GTPase
As shown in Fig. 5A, PLX4032 treatment increased HER3 and HER2 mRNAs in all six BRAF-mutant thyroid cancer cell lines tested .
bio-exp_0001.3
2014-09-26T12:18:43
2014-11-22T19:31:23
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.
bio.mskcc_0001.52
Cancer
cancer
Cancer
cancer
Shaw
B-Raf
-
EGFR
1128
50
SH3 domain
TFIIH
1994
carboxy-terminus
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
2015-02-07T10:09:52
MEK
CD72
bel_pmid_1066_0621.21334
10660621
2015-04-09T07:31:47
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.
CtBP1
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.
2015-06-15T14:29:24
pmid_1528_0923.100
15280923
2
5F
68
threonine
EGFR
CRB
0.01
ASPP2
GEF
bio.mskcc_0001.39
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).
2015-01-21T12:14:33
GEF
oligodeoxynucleotide
10
B-Raf
EGFR
2015-02-25T10:26:21
bmtr_0006.5
However, our results provide the first direct evidence for a protein that may stabilize nucleotide-free Ras in vivo.
serine
151
EGFR
bio.mskcc_0001.41
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).
2015-01-21T14:06:45
threonine
GDP
B-Raf
STAT3
1995
MEK
BCR
-
Ramos human lymphoblastoid
HER2
-
1990
Phosphatidylinositol 3-Kinase Beta
2015-01-25T16:48:03
bio.bmtr_0003.16
These findings were confirmed in a second cell line (Supplementary Fig. S5A).
3
pmid_1528_0923.75
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
2015-06-19T00:21:32
MTT
Dpp
Ras
1
-
Flag
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.
2014-12-22T16:19:51
bio.bmtr_0001.14
PP2A
MTT
KRAS
2015-10-22T10:03:55
bio.chicago_2015.18776
We compared cdc25A induction to that of cyclin E, which is regulated by E2F and Rb family members ( 4, 20, 45).
Cancer
cancer
1
8
FACS
N-terminal
2015-01-23T04:01:28
hKSR-2 selectively inhibited the Cot-mediated activation of MEK by 60%.
bio.bel_0002.11
Phosphorylation of ASPP2 by RAS/MAPK Pathway Is Critical for Its Full Pro-Apoptotic Function (PMC3847091)
bio.bmtr_0005.1
2015-01-06T07:32:43
bio.mskcc_0001.22
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).
2014-11-28T17:28:12
tyrosine
1
septin
C-terminus
Cancer
cancer
7A
2015-01-20T09:08:43
bio-kappa_0001.26
This series of reactions is reversed by rebinding of nucleotide , predominantly GTP , because of its higher concentration in the cell .
-
MEK
actin
B-Raf
protein phosphatase 2A
MDA-MB-468
ERK12
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>].
a_pmid_2488_5690.68
24885690
2015-06-10T00:40:15
Ras
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.
bio.bmtr_0004.11
2015-01-06T12:31:02
JAK1
2014-11-29T21:32:40
bio.mskcc_0001.26
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.
C-Raf
EGFR
B
2015-02-26T01:08:16
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).
bmtr_0007.7
-
serine
729
-
H-Ras
B-RAF
neurotrophin
bio.bmtr_0004.8
We obtained similar results using K-Ras (Supplementary Figure 6), indicating that the effects of monoubiquitination on Ras are not isoform-specific.
2015-01-06T11:02:39
EGFR
-42
IGF-IR
thyroid cancer
Thyroid_cancer
K-Ras
2015-01-25T15:36:32
bio.bmtr_0003.10
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.
2015-06-21T05:55:48
pmid_1528_0923.80
15280923
Six cell lines with different levels of EGFR expression were selected for treatment with PKI166.
B-RAF
urea
HER2
GTP
PLX4032
HER2
Axin
D347A
threonine
669
bio.bmtr_0004.3
2015-01-06T08:58:49
We next considered the effect of Ras monoubiquitination on GAP-mediated hydrolysis.
PI3K
K46^mA
RKO-E1
15280923
pmid_1528_0923.67
<sec-title level="2">Differences in activity of ERK1/2 in the breast cancer cell lines</sec-title>
2015-06-18T03:17:13
bio.chicago_2015.18724
2015-10-22T09:11:09
The Essential Activity of DSmurf Is Limited to the DPP Signaling Pathway
B-Raf
11
interrogative
2015-01-20T08:30:46
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
24885690
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).
2015-06-09T00:45:57
BRAF
2015-06-16T10:52:27
15280923
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
To identify the site(s) on the cytoplasmic domain of the EGFR that mediates its recruitment of PI3K-C2beta, a panel of receptor point mutations was expressed in HEK293 cells.
bio.chicago_2015.19311
2015-10-21T13:44:06
2015-04-14T14:59:38
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
bio.mskcc_0001.3
To activate the Raf proteins, autoinhibition mediated by the N terminus must be relieved and the kinase domain must adopt the active catalytic conformation
2014-11-03T19:35:08
Ras
bel_pmid_1069_9758.24188
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.
10699758
2015-04-11T06:31:13
ASPP1
2015-04-09T03:46:19
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.
10640734
bel_pmid_1064_0734.39804
C-Raf
ASPP2
2A
DNA
DNA DNA
B-Raf
FGFR3
GAP
4C
bio.bmtr_0005.16
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.
2015-01-07T03:17:37
2015-04-13T12:11:45
bel_pmid_1072_9607.86
These results are consistent with our previous data showing that PAF is able to translocate PKCa and PKCe from cytosol to plasma membrane
10729607
Raf
-
K46^mA
Cdc5
ERK12
-
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.
2015-10-20T09:27:46
bio.chicago_2015.18666
ERK
Ras
2015-02-07T10:17:49
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 .
2015-06-21T11:17:53
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
15280923
GTP
JAK
SRC-1
2B
C-RAF
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 ).
bel_pmid_1073_7606.22816
10737606
2015-04-14T08:35:13
ERK
U0126
4
GTP
2015-01-20T07:03:49
bio-kappa_0001.16
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 .
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.
2015-06-21T08:19:01
15280923
pmid_1528_0923.83
Saos2
bio.mskcc_0001.28
2015-01-20T11:13:17
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).
TCF
bio.mskcc_0001.9
2014-11-06T21:57:03
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.
ERBB3
C-Raf
Wntbeta-catenin
GTP
2015-06-18T06:52:55
pmid_1528_0923.72
15280923
<sec-title level="2">Elevated ERK activity does not necessarily correlate with the status of EGFR and HER2 in breast cancer cells</sec-title>
1
BCR
B-Raf
These results are consistent with a model in which ubiquitination of Lys147 (or Lys117), destabilizes GDP binding, allowing spontaneous GDP/GTP exchange.
2014-12-18T17:10:57
bio.bmtr_0001.13
Colorectal_cancer
colorectal cancer
bio.chicago_2015.18079
2015-10-28T04:55:26
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.
ASPP2
B-Raf
PKI166
prefoldin
15280923
Growth inhibition was determined from the results of MTT assays, comparing PKI166 treated cells with cells exposed to medium with 0.1% DMSO.
2015-06-21T07:44:10
pmid_1528_0923.82
-
N-terminus
E1 E-box
ERBB3
2
RBW-1
Ksr1
Axin
ASPP2
B-Raf
interrogative
ASPP2
Cdc11
4
MEK
GTP
2015-10-27T07:35:52
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).
bio.chicago_2015.17180
PLX4032
Erk
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>).
15280923
2015-06-15T14:13:28
NGH.S4
p19INK4D
1991
bmtr_0006.2
2015-02-25T09:23:27
Ras, like all GTPases, cycles between an inactive GDP-bound state and an active GTP-bound state.
Guichet
GFP
ERK
GSK3 beta
carcinoma
2014-12-09T22:13:53
bio.bmtr_0001.5
His-ubiquitinated K-Ras was subsequently purified with anti-Flag resin.
Ksr
2015-01-06T13:41:51
bio.bmtr_0004.20
This chemical ligation strategy will likely be useful for the study of other monoubiquitinated proteins.
EGFR
lysine
147
Raf-1
ASPP1
HER2
-
1
PLX4032
1.4
1
All other activities, including the ability to bind regulators, were largely preserved and our kinetic modeling suggests that the GAP defect will dominate.
2015-01-06T03:44:41
bio.bmtr_0004.25
K46^mA
BRAF
Importantly, we show that wild-type B-RAF can also activate C-RAF.
bio.bel_0002.3
2014-09-29T15:10:36
a_pmid_2488_5690.53
2015-06-09T10:21:30
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>].
24885690
21
bio.mskcc_0001.1
2014-11-03T12:55:43
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.
tyrosine
7
2015-01-06T02:13:25
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
Hence ASPP2 can be phosphorylated at serine 827 by MAPK1 in vitro.
bio.bmtr_0005.17
2015-01-07T04:57:02
caspase
PKCe
ASPP2
VEGFR-3
37
36
actin
2014-12-22T16:52:11
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
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 .
bio-kappa_0001.3
2014-09-27T15:35:13
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).
2014-11-29T21:20:25
GI101A
6A
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 ).
bio.chicago_2015.18587
2015-10-21T12:48:06
HER3
-
PKI166
2015-06-10T00:22:21
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
5D
Tyrosine
tyrosine
B-Raf
2015-01-07T01:19:03
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.
1B
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).
2014-11-16T20:11:46
MEK
CtBP1
PKI166
We show that IL-6 triggers selective activation of SHP2 and its association with RAFTK in Dex-treated MM cells.
10880513
bel_pmid_1088_0513.7274
2015-04-16T13:17:28
HER3
2014-11-16T18:19:06
bio.mskcc_0001.17
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.
753
threonine
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.
15280923
pmid_1528_0923.103
2015-06-16T10:44:12
We observed analogous results in CHO-KI cells expressing wild-type ERBB3 in combination with wild-type or T677A mutant HER2 (Figure 6B).
bio.bmtr_0002.13
2014-12-15T18:12:14
-
PMC3437993
2015-01-19T01:53:15
bio.ras_0003.2
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 .
26
gamma-secretase
Childs
27
JM domain
B-Raf
GAP-334
MDA-MB-231
tyrosine
G12V
2015-06-09T23:42:19
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).
24885690
a_pmid_2488_5690.60
V600E
MEK
B-Raf
-
B-Raf
-
cdc25A
-
L521P
EGFR
RBD
p53
2B
EGFR
K-Ras K-Ras4B
24
23
SHOC2
DLT
Hydrogen_peroxide
H2O2
SKBR3
21
C-Raf
Ras17N
-
PI3KAKT
PC
S365A
2015-01-06T12:53:31
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
BRAF
It is also intrinsically very slow and thus has to be accelerated by GTPase - activating proteins ( GAPs ) .
2015-01-20T08:41:56
bio-kappa_0001.24
1
HER3
B-Raf
-
Here we show that monoubiquitination decreases the sensitivity of Ras to GAP-mediated hydrolysis.
2015-01-06T13:33:35
bio.bmtr_0004.18
Hirano
-
HER2
2014-11-22T19:29:50
bio.mskcc_0001.51
These residues are phosphorylated by activated ERK in vitro,
2
bio.bmtr_0001.10
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.
2014-12-18T10:39:24
EGFR
-
-
a_pmid_2488_5690.63
24885690
PUMA was found to be highly abundant specifically in serum starved RBW-1 (Figure <xref ref-type="fig" rid="F2">2</xref>H).
2015-06-10T00:00:07
ATM
2015-06-08T05:01:37
a_pmid_2488_5690.10
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.
24885690
G12V
actin
Ras
bcl-2
PI3K
729
serine
200
2015-01-20T15:12:00
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
2015-06-09T10:05:20
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
24885690
19
DNA
1
overexpressions of cyclin D1 or bcl-2 inhibited only differentiation or apoptosis, respectively
bel_pmid_1066_6199.2154
10666199
2015-04-09T07:44:01
The guanine nucleotide-binding switch in three dimensions .
2015-01-20T08:03:03
bio-kappa_0001.20
2015-10-27T08:07:18
bio.chicago_2015.17227
At the nucleus, PKC betaII directly phosphorylates the nuclear envelope polypeptide lamin B at sites involved in mitotic nuclear lamina disassembly ( 8-10).
guanine nucleotide exchange factor
bio.bmtr_0002.7
2014-12-15T14:06:48
Mutation of T669 and T677 abrogates MEK inhibitor-induced suppression of ERBB3 Activation
750
serine
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 ) .
2015-02-07T10:47:07
bio-exp_0001.10
-
ERK12
-
2015-10-21T03:50:36
bio.chicago_2015.19306
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.
Sasaki
pmid_1528_0923.88
2015-06-21T10:57:30
<sec-title level="2">PKI166 inhibits phosphorylation of EGFR and HER2 in breast cancer cells</sec-title>
15280923
2015-04-09T06:35:04
Furthermore, the hCdc14 phosphatases were found to dephosphorylate p53 specifically at the p34(Cdc2)/clb phosphorylation site (p53-phosphor-Ser(315)).
10644693
bel_pmid_1064_4693.7794
bmtr_0007.10
2015-02-26T01:39:26
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).
p120GAP
151
serine
ERK12
HER3
CM
MEK
2015-02-26T02:06:09
The phospho-specific antibody for ASPP2 is specific as knockdown of ASPP2 resulted in a lack of detection of phospho-ASPP2.
bmtr_0007.11
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).
bio.bel_0002.8
2015-01-23T02:59:24
G466A
GSK-3beta
oligodeoxynucleotide
T669A
bio.bmtr_0003.4
2015-01-23T15:09:03
As shown in Fig. 5A, PLX4032 treatment increased HER3 and HER2 mRNAs in all six BRAF-mutant thyroid cancer cell lines tested.
GTP
LiCl
ERK12
Ras
bio.bmtr_0002.14
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).
2014-12-15T18:52:18
Shp2
CtBP
Ras
Aberle
10699758
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].
2015-04-09T09:06:02
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.
bel_pmid_1064_0734.39802
2015-04-09T03:22:23
10640734
5A
actin
bio-exp_0001.12
2015-02-05T12:19:53
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.chicago_2015.18159
2015-10-20T09:28:01
This is supported by the in vitro observations that Dvl inhibits GSK-3beta-dependent phosphorylation of Axin, APC, and beta-catenin in the Axin complex, although the bindings of GSK-3beta, beta-catenin, and APC to Axin are not changed, and that Dvl does not affect GSK-3beta activity to phosphorylate the peptide substrate ( 22, 26).
RBOW
-1
2015-04-09T06:20:57
10640734
bel_pmid_1064_0734.39830
Coligation of CD72 with BCR showed a reduced Ca2+ flux compared to that with BCR ligation alone in spleen B cells (Fig. 6D).
10851026
When either primary or OB1 osteoblasts are induced to differentiate, FGF signaling inhibits expression of alkaline phosphatase, and blocks mineralization.
bel_pmid_1085_1026.8694
2015-04-16T17:01:37
Histone 2B
2015-10-21T10:35:19
bio.chicago_2015.18396
Axin enhances the phosphorylation of beta-catenin by GSK-3beta by positioning GSK-3beta close to beta-catenin, resulting in the inhibition of the Wnt signaling pathway ( 32).
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.chicago_2015.18750
2015-10-22T09:25:20
34
to prevent the additional stabilization of U2AF65 binding conferred by the interaction between U2AF35 and the AG dinucleotide.
2015-10-27T09:03:36
bio.chicago_2015.17446
Ras
15280923
2015-06-18T05:40:38
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.
pmid_1528_0923.70
serine
2+
ASH1
2015-06-15T14:47:46
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.
15280923
pmid_1528_0923.101
Pbx
tyrosine
The phosphorylated ASPP2 fragment by MAPK1 was digested by trypsin and fractioned on a high performance liquid chromatography (HPLC).
bio.bmtr_0005.13
2015-01-07T02:45:06
ERK
ATF-2
-
Hydrogen_peroxide
H2O2
bio.chicago_2015.18744
2015-10-22T09:17:29
Alternatively, auxilin might bind much more weakly to Hsc70 in ADP than ATP.
MDA-MB-231
GAP
thioredoxin
bio.bmtr_0004.23
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.
2015-01-06T02:48:52
bio-kappa_0001.6
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 ) .
2015-01-20T01:34:52
cyclin E
2015-10-28T05:25:16
bio.chicago_2015.18127
Axin also blocks beta-catenin-mediated transcription in colon cancer cells that have a mutation in the adenomatous polyposis coli gene.
2015-04-09T05:20:31
bel_pmid_1064_0734.39820
10640734
Thus, expression of CD72 appears to negatively regulate BCR-mediated Ca2+ mobilization in K46^mA cells.
The ASPP1 sites are at residues 671 and 746, and the ASPP2 sites are at residues 698 and 827 (Figure 1A).
2015-01-07T02:54:52
bio.bmtr_0005.8
4.5
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.
2015-10-27T15:27:57
B-Raf
cyclin D1
5E
bio.bmtr_0001.2
2014-12-03T21:45:59
We utilized an unbiased mass spectrometry-based approach to identify ubiquitination sites of Ras.
C-terminus
PUMA
2014-12-15T14:52:21
bio.bmtr_0002.9
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.
-
BCR
2015-01-19T06:56:05
bio.ras_0003.6
H-Ras ubiquitination sites were also determined by the same approach .
dCBP
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).
bio.bmtr_0004.4
2015-01-06T09:08:59
phosphopeptide
C-Raf
Lu
365
serine
HER2
K-Ras
-
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>).
pmid_1528_0923.106
2015-06-16T11:03:57
15280923
JM domain
mRNA
bio.mskcc_0001.43
2014-11-21T12:50:26
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.
ASPP2
293T
GSK-3beta
cancer
Cancer
Rap1
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>].
2015-06-09T10:07:28
a_pmid_2488_5690.52
24885690
DNA
DNA
bio.bmtr_0005.12
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.
2015-01-07T02:20:07
trypsin
R4 precursor
SUM149
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.
2015-02-07T09:19:06
bio.bel_0002.13
histidine
bio-kappa_0001.4
2015-01-19T06:33:33
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 ) .
PKI166
C
60
Cancer
cancer
bio.mskcc_0001.4
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).
2014-11-03T20:16:00
tyrosine kinase Fyn
MDA-MB-231
bio.bmtr_0002.18
2015-01-21T17:32:05
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).
2015-10-27T08:19:07
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
-
T669A
threonine
multiple myeloma
10
cdk4
ERK
Ras17N69N
-
Phosphorylation of ASPP2 by RAS/MAPK Pathway Is Critical for Its Full Pro-Apoptotic Function (PMC3847091)
bmtr_0007.1
2015-02-26T00:31:54
2015-04-09T07:48:56
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.
bel_pmid_1066_6199.28424
10666199
etoposide
-
Groucho
Cancer
cancer
2015-06-18T04:12:42
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.
GTP
alanine
bio-exp_0001.4
Similar results were found following treatment with the MEK inhibitor AZD6244 ( not shown ) .
2015-01-23T04:12:10
B-Raf
CHO-KI
FAK
15280923
pmid_1528_0923.99
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.
2015-06-15T14:19:24
15280923
pmid_1528_0923.79
<sec-title level="2">PKI166 inhibition of breast cancer cell proliferation</sec-title>
2015-06-21T05:42:15
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.
2015-04-09T04:01:27
bel_pmid_1064_0734.39810
10640734
N-terminus
ATP
B-Raf
bio.chicago_2015.17743
2015-10-28T00:41:06
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 ).
V600E
2015-01-06T13:16:30
bio.bmtr_0004.16
Passage 1-2 (Discussion/Conclusion)
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
2014-11-03T19:18:55
Ras
adenomatous polyposis coli
-
OB1
61L
B-Raf
ERK
-
threonine
669
Mek
77
cysteine
2015-01-06T07:18:02
bio.bmtr_0004.27
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.
JAK1
ASPP2
-
N terminus
EGFR
ATM
CtBP2
ASPP2
2015-10-22T08:52:41
bio.chicago_2015.18717
Our results demonstrate that the chromosome condensation defect caused by perturbed ISWI function is mediated through the NURF complex.
29
27
30
V600E
26
22
IGF-I
Jou
24885690
a_pmid_2488_5690.57
2015-06-09T23:29:10
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.
46
RAF_kinase
RAF
BRAF
megakaryocyte
bel_pmid_1074_7872.20016
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.
2015-04-14T14:11:40
10747872
CD72
Serial deletions identified a minimal HER3 promoter retaining transcriptional response to vemurafenib and AZD6244, which was located between -401 and -42 bp (Fig. 5C).
bio.bmtr_0003.8
2015-01-25T15:10:43
Yu
NF1-333
MDA-MB-468
2015-06-09T05:16:43
24885690
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>].
a_pmid_2488_5690.43
bio.bmtr_0001.18
2014-12-22T15:16:55
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.
B-Raf
1997
10744722
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).
bel_pmid_1074_4722.21126
2015-04-14T11:42:05
colorectal cancer
Colorectal_cancer
The most frequently mutated oncogenes in the deadliest cancers responsible for human mortality are KRAS , PIK3CA and BRAF .
bio.ras_0001.1
2014-08-13T14:22:25
Cancer
cancer
fibronectin
interrogative
For B-Raf, previous work by Brummer et al. (3) identified the C-terminal S750 and T753 residues as sites phosphorylated by activated ERK.
2014-11-22T19:09:15
bio.mskcc_0001.49
Axin
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
2015-04-16T17:42:59
10851055
These multiple Ras functions depend on its binding to a range of functionally diverse effector molecules such as Raf , PI3K , AF6 and RASSFs ( 1 ) .
bio.ras_0002.2
2015-01-13T20:53:19
Flag
1C
PMC3847091
-
brinker
-
EGFR
B-Raf
C-terminus
2015-01-21T13:09:21
bio.mskcc_0001.40
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.
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.
24885690
2015-06-09T23:32:53
a_pmid_2488_5690.58
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).
24885690
a_pmid_2488_5690.61
2015-06-09T23:49:47
Accordingly, knockdown of CTBPs acutely induced HER3 expression and phosphorylation in thyroid cancer cells.
2015-01-25T17:07:41
bio.bmtr_0003.19
Pin1
bio.bmtr_0003.20
2015-01-25T17:14:26
MAPK inhibition may dictate a chromatin redistribution of these repressors, and thus activate HER3 transcription.
bio.ras_0002.3
2015-01-14T04:48:20
The enhancement of specific effector pathways plays a critical role in maintaining an appropriate biological response ( 8 ) .
steroidnuclear receptor
24885690
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.
2015-06-09T05:39:53
-
4
MAPK1
8
CTD-S2-P
-
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.
2015-01-20T14:44:20
bio.mskcc_0001.31
5D
N-terminus
breast cancer
Breast_cancer
CTD
2015-10-21T14:06:37
bio.chicago_2015.19345
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.
Passage 1-1 (Results)
bio.bmtr_0005.2
2015-01-06T07:47:04
filamin
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 .
2014-09-19T16:48:49
Axin
Rho
PAF
6
It has recently been shown that oncogenic RAS can enhance the apoptotic function of p53 via ASPP1 and ASPP2.
bio.bmtr_0005.3
2015-01-06T07:52:16
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.
2015-02-05T10:37:17
bio.bel_0002.6
PKI166
bmtr_0007.5
antibody, a non-radioactive in vitro phosphorylation assay was performed on the purified GST-ASPP2 fragment (693-1128) with recombinant MAPK1.
2015-02-26T01:01:36
G466A
RBD
CMV
Gp150
U0126
2015-06-21T10:26:54
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.
pmid_1528_0923.87
15280923
bmtr_0007.2
A synthetic peptide encoding amino acids 824-832, with a phosphoserine at residue 827, was used to raise antibodies.
2015-02-26T00:42:26
ERK12
-
PKC
Threonine
threonine
BRAF
bio.chicago_2015.18761
2015-10-22T09:59:43
During gastrulation, DLT may first form a complex with CRB to target it to the apical domain.
bio-kappa_0001.10
One of the most abundantly expressed PSPs , protein phosphatase 2A ( PP2A ) , can regulate the Raf / Mek / Erk pathway both positively and negatively .
2015-01-20T03:41:50
1500
PUMA
C-Raf
ASPP2
Engrailed
bio.bmtr_0001.4
His-ubiquitinated proteins were purified by Co2+ metal affinity chromatography in 8M urea denaturing conditions.
2014-12-09T14:55:44
receptor tyrosine kinase
Raf
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
2015-10-21T00:52:45
C-Raf
2015-04-14T13:16:27
10744722
bel_pmid_1074_4722.21168
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).
bel_pmid_1069_9758.34686
10699758
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].
2015-04-11T07:06:57
EGFR
PP1C
BRAF
Chk2
CD72
APP
pmid_1528_0923.85
However, not all of the high EGFR-expressing lines were sensitive to PKI166.
15280923
2015-06-21T09:24:57
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).
2014-12-15T15:05:31
bio.bmtr_0002.10
cadherin
Ras
bio.ras_0003.5
2015-01-19T05:43:28
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 ) .
1
hemin
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).
2015-06-09T05:31:04
a_pmid_2488_5690.46
24885690
ERK
threonine
669
2
BRAF
2015-01-20T22:53:13
bio.mskcc_0001.33
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.
2014-11-21T12:13:54
bio.mskcc_0001.19
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).
Phospho-specific antibodies confirmed that treatment with AZD6244 inhibited phosphorylation of T669 of EGFR and the analogous T677 of HER2 (Figure 5A).
2014-12-14T21:08:29
bio.bmtr_0002.5
BRAF
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.
2015-10-21T09:43:28
bio.chicago_2015.18196
HER3
-
10737606
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.
2015-04-13T14:43:10
bel_pmid_1073_7606.7132
U2AF65
carcinoma
serine
621
GTP
bio.bmtr_0003.9
2015-01-25T15:28:42
This region does not contain any predicted FoxO binding sites.
827
serine
669
threonine
vemurafenib
Cancer
cancer
SPT5
bio.mskcc_0001.12
2014-11-09T20:58:01
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).
RASMAPK
cysteine
casein kinase I
827
serine
G3 box
Axin
PKI166
1B
6
2014-12-09T22:54:17
bio.bmtr_0001.7
H-Ras ubiquitination sites were also determined by the same approach.
thyroid cancer
Thyroid_cancer
750
serine
S1
cdk6
GAP
B-Raf
a_pmid_2488_5690.44
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).
2015-06-09T05:24:19
Ras
cytokine
Ras
-
STAT3
-1
5.0
Therefore, mUbRas is insensitive to GAP-mediated regulation, similar to an oncogenic Ras-G12V mutation.
bio.bmtr_0004.7
2015-01-06T10:42:11
MEK
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.
2014-12-22T16:27:59
bio.bmtr_0001.15
TRX
6
2
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 ).
bio.chicago_2015.19139
2015-10-20T14:25:08
MAPK
Raf
U0126
PIK3CA
CtBPs have also been described to negatively regulate transcriptional activity of the HER3 promoter in breast carcinoma cell lines (30).
2015-01-25T16:16:54
bio.bmtr_0003.12
U0126
bio.mskcc_0001.47
Previous studies have found that both the C-Raf and B-Raf proteins are targets of ERK-dependent feedback phosphorylation
2014-11-22T17:41:50
GDP
HER2
Cell-biological phenotypes related to mutant <i>BRAF</i>
24885690
2015-06-09T09:55:59
a_pmid_2488_5690.48
GDP
K-Ras
BMP-1
BRAF
T669A
beta-catenin
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 .
2015-01-20T04:54:37
bio-kappa_0001.11
H-Ras
mRNA
ERK12
choline
CKI
C-Raf
1
Mammalia
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>].
2015-06-09T00:36:59
a_pmid_2488_5690.38
24885690
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>).
15280923
2015-06-21T05:31:55
pmid_1528_0923.78
RNA pol II
Ras
EGFR
ASPP2
30
Chk1
bio.bmtr_0002.8
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.
2014-12-15T14:16:53
bio.ras_0003.1
We utilized an unbiased mass spectrometry - based approach to identify ubiquitination sites of Ras .
2015-01-19T01:16:07
1
threonine
753
-
2015-10-21T13:22:15
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.
bio.chicago_2015.18675
serine
315
PI3KAKT
3B
Breast_cancer
breast cancer
-
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.
2015-10-25T12:49:36
interrogative
-
HER3
bel_pmid_1074_4722.15500
2015-04-14T11:32:28
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).
10744722
beta-catenin
C-Raf
-
bio.bmtr_0001.3
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.
2014-12-03T21:53:14
Tomlinson
36
Rlf
G1 box
guanine nucleotide exchange factor
2+
147
lysine
zinc finger
ASPP2
Gln61
HER2
2000
4A
U0126
bio.chicago_2015.18689
By definition, PLD catalyzes the hydrolysis of PC to PA and choline.
2015-10-21T13:36:50
147
lysine
cyclin D1
ASPP2
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 .
bio-kappa_0001.25
2015-01-20T09:07:33
Dulbecco
Ras
0.5
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
bel_pmid_1079_1191.20850
2015-04-17T04:02:44
MAPK
MDA-MB-435
338
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.
15280923
2015-06-21T09:55:03
pmid_1528_0923.86
151
serine
PDTC
ASPP2
669
1
2015-04-11T01:45:18
10677502
bel_pmid_1067_7502.21952
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
GTP
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.
2014-12-14T20:37:51
bio.bmtr_0002.3
2A
BRAF
−−
-
bio-exp_0001.15
2015-02-05T12:14:53
These findings were confirmed in a second cell line ( Supplementary Fig. S5A ) .
EGFR
1997
-
Ras
2014-12-18T12:35:31
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).
bio.bmtr_0001.11
1B
PKI166
BRAF
2
U0126
Ras
E1A-RG2
8
70
K-Ras
Ras
MAPK
ERK12
A New Dimension to Ras Function: A Novel Role for Nucleotide-Free Ras in Class II Phosphatidylinositol 3-Kinase Beta (PI3KC2β) Regulation (PMC3441633)
2015-02-25T09:09:15
bmtr_0006.1
multiple myeloma
8
1
PI3KC2β
bio.chicago_2015.18464
( c) Axin inhibits secondary axis formation induced by CKI .
2015-10-21T10:41:59
However, immature osteoblasts respond to FGF treatment with increased proliferation, whereas in differentiating cells FGF does not induce DNA synthesis but causes apoptosis.
10851026
2015-04-16T14:25:22
bel_pmid_1085_1026.8692
16
6
breast cancer
Breast_cancer
1D
Sos
oxaliplatin
K375M
bio-kappa_0001.7
2015-01-20T01:58:10
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 .
2+
BCR
LIF
MDA-MB-231
GTPase
2015-06-09T10:02:11
a_pmid_2488_5690.50
24885690
Expectedly, decreased serum concentrations led to lower proliferation rates in these cells, but exponential growth was sustained under all applied conditions.
BR
-
-
bio.mskcc_0001.48
In the case of C-Raf, six sites of feedback phosphorylation have been identified, five of which are direct targets of activated ERK (8)
2014-11-22T19:04:35
70
1988
2015-06-21T12:18:34
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).
15280923
C-Raf
C-Raf
Among tested agents, the B-Raf inhibitor dabrafenib was found to induce a strong V600E-dependent shift in cell viability.
24885690
2015-06-08T23:25:37
a_pmid_2488_5690.11
345
367
32
75
EGFR
MAPK1
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).
bio.bmtr_0001.8
2014-12-05T20:16:13
B-Raf
V600E
dup7q21q36
3
2015-01-21T17:03:45
When endogenous EGFR was replaced with EGFR (exon19del) wild-type at T669, MEK inhibition led to significant feedback activation of ERBB3/PI3K/AKT signaling (Figure 6C).
bio.bmtr_0002.17
-
bio.chicago_2015.17176
2015-10-27T05:34:49
dSir2 Interacts Genetically with Hairy Embryos derived from mothers transheterozygous for hairy and dSir2 mated to wild-type males exhibit moderate
V600E
1
1A
HER2
brk
C-Raf
ERBB3PI3KAKT
RKO
K-Ras
1
2
6
GSK
20
TCF-1
154
HER2
B-RAF
MKK2
10744722
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).
bel_pmid_1074_4722.21170
2015-04-14T13:31:50
E2F
SUM149
Cancer
cancer
Dual blockade of EGFR and ERK1/2 phosphorylation potentiates growth inhibition of breast cancer cells (PMID:15280923)
2015-06-18T01:10:09
15280923
pmid_1528_0923.1
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.
bio.bmtr_0002.6
2014-12-14T21:17:43
14-3-3
GTP
2015-04-13T13:49:55
10729607
bel_pmid_1072_9607.22074
Suppression of the PAF effects by calphostin C, a PKC inhibitor, suggests that PKC is an upstream activator of FAK
HER2
1
2
1
bio.chicago_2015.19058
Overexpression of cdc5delta N induces a disturbance in septin ring structures and Cdc5 interacts with two septins, Cdc11 and Cdc12, in a polo-box - dependent manner.
2015-10-20T05:40:46
621
serine
tyrosine kinase receptor
1
6C
RKO
S1C
MLC-pep
MAPK
50
Ras
MDA-MB-468
IL-6
AZD6244
RAS
Finelli
bio.ras_0001.3
Ras acts as a molecular switch that is activated upon GTP loading and deactivated upon hydrolysis of GTP to GDP .
2014-08-13T16:08:20
2014-08-13T20:35:42
bio.ras_0001.9
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 .
BRAF
bio-exp_0001.2
2014-09-26T12:18:16
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 .
neurotransmitter transporter
Raf
14-3-3
31
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
2015-06-18T06:26:09
15280923
bel_pmid_1064_0734.39826
2015-04-09T05:59:50
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
These results suggest that CBP can bind to various transcription factors of the ATF/ CREB family through the b-ZIP domain.
bio.chicago_2015.17757
2015-10-28T01:04:42
MAPK1
BMP-2
18
-
Eagle
MEKERK
B-Raf
Ras
Ras
MKK
beta-cateninTcf
G1 phase
Dpp
Axin
-
Drosophila
Drosophila
13.434
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 ) .
2015-01-14T07:23:18
bio.ras_0002.5
TPO
bio.bmtr_0005.15
The fractions representing these radioactive peaks were analysed by mass spectrometry.
2015-01-07T03:12:21
Ras
brk
-
G box
5
A polyclonal antibody NGH.S4 was purified by affinity column purification.
bmtr_0007.3
2015-02-26T00:55:09
ERK12
1
3
13
15
12
First, PR facilitates binding of NF1 by an ATP-dependent process that results in marked reduction of the linking number of chromosomal DNA.
bio.chicago_2015.18265
2015-10-21T10:13:09
MAPK
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.
bio.bmtr_0004.5
2015-01-06T10:21:04
2015-04-13T12:23:45
bel_pmid_1072_9607.18666
10729607
Eosinophils Human Superoxide production Human Transmigration through epithelial cells Human Transmigration through Matrigel Human CD11b/CD18 (Mac-1) translocation, degranulation Human IL-8 release
Whether PKC regulation of DAT and other neurotransmitter transporters is due to direct phosphorylation of the transporter remains unclear.
2015-10-25T13:07:12
bio.chicago_2015.17152
55
30
bmtr_0006.8
These data suggest that PI3KC2β binding to nucleotide-free Ras in vivo may prevent loading of nucleotides onto Ras.
2015-02-25T10:59:27
Because PLD activates PKC through the formation of diacylglycerol in VSMCs,47 PLD also may contribute to this suppression.
bio.chicago_2015.17114
2015-10-25T12:59:51
Ras
CtBP2
Raf
-
RASSF
stauro
14
16
-
76
2
EGFR
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).
bio.chicago_2015.18552
2015-10-21T12:34:15
Ras
449
2C
Ras
brinker
8505C
1
actin
151
serine
bmtr_0006.10
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.
2015-02-25T12:36:53
RAS
GSK-3beta
threonine
669
PMC3847091
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.
2015-04-14T12:32:00
10744722
bel_pmid_1074_4722.21132
bel_pmid_1068_1535.5746
2015-04-11T02:11:44
10681535
We found that TPO stimulation or Ha-Ras G12V expression led to up-regulation of cyclin D1, cyclin D2, and cyclin D3 expression.
IL-6
RBW-1
2015-04-11T02:21:10
10681535
bel_pmid_1068_1535.24496
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.
2015-06-08T23:54:05
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
GTPase
cancer
Cancer
2015-06-09T23:22:38
24885690
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.
a_pmid_2488_5690.56
1B
serine
15
-
trypsin
447
serine
bio.bmtr_0001.1
Sasaki et al., “Ubiquitination of Ras enhances activation and facilitates binding to select downstream effectors” (PMC3437993)
2014-12-03T18:05:22
epsilon
2015-02-25T12:27:05
Although current methods do not allow for detection of nucleotide-free GTPases in vivo, our BiFC results provide additional support for our model.
bmtr_0006.9
DNA
DNA
GTP
2015-01-25T14:28:31
bio.bmtr_0003.6
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).
677
threonine
PAFR
II
CTD-S5-P
PUMA
4-hydroxytamoxifen
PKI166
dSir2
AMR-Role
B-Raf
central armadillo repeat
365
serine
bio-kappa_0001.2
2014-09-26T12:38:07
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 .
2015-06-16T10:36:10
pmid_1528_0923.102
15280923
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).
interleukin-6
5
serine
In addition, we found that Rheb inhibits the association of B-Raf with H-Ras.
2015-01-23T03:55:41
bio.bel_0002.10
EGFR
EGF receptor
1999
2014-11-24T15:21:00
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).
bio.mskcc_0001.57
bio.bmtr_0004.12
2015-01-06T12:43:54
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.
bio.bmtr_0005.5
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.
2015-01-07T00:52:41
2015-01-21T07:29:54
bio.mskcc_0001.37
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.
2015-04-09T06:55:11
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.
10648414
2
B-Raf
pmid_1528_0923.94
2015-06-15T12:42:09
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.
15280923
cancer
Cancer
ERK
B-Raf
threonine
677
FGF signaling
-
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 19del) wild-type at T669, or EGFR (exon 19del) carrying a T669A mutation.
2015-01-21T16:11:03
bio.bmtr_0002.15
0.5
1
bio.bmtr_0004.2
2015-01-06T08:06:39
Passage 1-1 (Results)
B-Raf
cyclin D2
-
GDP
5A
<sec-title level="2">Constitutive ERK1/2 phosphorylation as a potential escape mechanism from inhibition by PKI166</sec-title>
2015-06-21T12:11:40
15280923
pmid_1528_0923.91
-401
Cds1
ZFN217
PKCa
2015-10-22T11:45:49
bio.chicago_2015.19022
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).
3C
HER2
bio-kappa_0001.15
2015-01-20T06:38:55
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 .
threonine
753
bio-exp_0001.9
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 .
2015-02-07T10:41:21
MDA-MB-435
8
10744722
2015-04-14T11:11:23
bel_pmid_1074_4722.15498
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.
cancer
Cancer
1B
bio.bmtr_0004.19
A major advance was our ability to easily generate mUbRas, modified at a single site, in a form suitable for detailed biophysical studies.
2015-01-06T13:36:10
lysine
117
colorectal cancer
Colorectal_cancer
1
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).
2015-01-25T15:59:16
bio.bmtr_0003.11
K-Ras
2015-06-21T11:00:46
15280923
pmid_1528_0923.89
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.
729
serine
bmtr_0006.11
2015-02-26T00:19:31
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).
JAK2
PLX4032
EGFR
C-Raf
PUMA
-
dabrafenib
3
65
1
B-Raf
GST-ASPP2
EGFR
proline
bio.mskcc_0001.30
The proteins were then expressed in NIH 3T3 cells and examined for their abilities to alter cell morphology and induce focus formation.
2015-01-20T14:21:50
V600E
HKe3 ER
HER3
BCR
GTP
4
K-Ras
bHLH
2C
C-Raf
-
AZD6244
2014-12-22T15:36:10
bio.bmtr_0001.20
However, a much greater fraction of the ubiquitinated-K-Ras was pulled down by the GST-RBD (Fig. 2C and fig. S1D).
Cancer
cancer
Jak3
1
1
PLX4032
RAS
2
ERBB3
2015-01-25T16:32:44
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).
bio.bmtr_0003.14
bmtr_0006.3
2015-02-25T09:34:42
The transition from the inactive to active state requires formation of nucleotide-free Ras through the action of exchange factors.
BRAF
G1
Ras
1-1
S729A
bio.bmtr_0005.20
2015-01-07T05:23:11
Moreover, the RAS-ASPP interaction enhances the transcription function of p53 in cancer cells [2].
ASPP2
KSR1
25
ERK
10640734
2015-04-09T05:27:53
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.
bel_pmid_1064_0734.39822
a_pmid_2488_5690.64
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>].
2015-06-10T00:05:29
24885690
-
RAS
beta-catenin
SKBR3
2015-10-21T02:14:06
bio.chicago_2015.19256
Towards the center of the gradient, high levels of Dpp signaling strongly repress brk transcription.
c
104
lysine
ASPP2
5C
bio-exp_0001.13
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 ) .
2015-02-07T09:16:39
Ras
MEK
bel_pmid_1074_7872.21236
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.
10747872
2015-04-14T14:46:59
Unlike WT B-Raf, oncogenic B-Raf proteins have been shown to heterodimerize constitutively with C-Raf in a Ras-independent manner (11).
bio.mskcc_0001.21
2014-11-21T12:49:56
FGF
Breast_cancer
breast cancer
PMC3515079
G76C
2
Cancer
cancer
1128
693
N-terminus
PKI166
-42
STAT3
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
2015-10-28T03:02:13
1B
interrogative
B-Raf
C
GATA-1
-
bel_pmid_1072_9607.19490
10729607
2015-04-13T13:35:19
PAF induced tyrosine phosphorylation and activation of focal adhesion kinase (FAK) in human endothelial cells derived from vein umbilical cord
E2F
0.1
2
pmid_1528_0923.96
15280923
2015-06-15T13:52:51
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.
B-Raf
2015-10-28T03:44:52
ILK also appears to regulate muscle differentiation by activating Erk, which suppresses transcription factors required for myogenic differentiation ( Huang et al., 2000).
bio.chicago_2015.18005
histidine
13
Extracellular_signal-regulated_kinases
ERK12
bio.bmtr_0004.1
Site-Specific Monoubiquitination Activates Ras by Impeding GTPase Activating Protein (PMC3537887)
2015-01-06T01:27:24
D594G
677
threonine
3
EGFR
-
Cancer
cancer
G466A
Shimell
401
threonine
Turke
B-Raf
PLD
interrogative
2015-10-21T10:22:56
Axin is also phosphorylated by GSK-3beta and stabilized by its phosphorylation in contrast to beta-catenin ( 22), and the phosphorylation increases the binding of Axin to beta-catenin ( 23, 24).
bio.chicago_2015.18319
guanosine triphosphatase
3C
DNA
K46^mA
50
Raf
S5A
-
calponin
EGF
PKI166
445
serine
2015-04-09T07:11:52
bel_pmid_1066_0621.6864
10660621
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.
ERK
6D
FGFR3
-
This result suggests that Axin binding to both GSK-3beta and beta-catenin is necessary for inhibition of Lef-1 reporter gene transcription.
2015-10-21T09:35:41
bio.chicago_2015.18186
STAT3
2015-01-20T00:43:24
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 .
bio-kappa_0001.5
-
MDA-MB-231
ERK
lamin B
1A
NGF
GTP
urea
JAK2
JM domain
2014-11-21T12:36:32
These findings support a model whereby feedback phosphorylation disrupts Raf heterodimerization.
bio.mskcc_0001.20
B
pmid_1528_0923.109
15280923
2015-06-16T11:50:30
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.
Ras
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
2015-02-25T10:43:42
RKO
HER3
ERK
CD72
GSK-3beta
147
1128
5
B-Raf
2015-10-28T02:49:19
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.
2+
cyclin D3
trypsin
IGF-IR
Raf-1
threonine
5F
Myc
HER3
EC
Colorectal_cancer
colon cancer
bio.bmtr_0005.7
Interestingly, we observed two conserved putative MAPK phosphorylation sites in ASPP1 and ASPP2.
2015-01-07T02:19:05
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
2015-01-21T15:50:56
bio.mskcc_0001.56
HER2
PMC3651738
bio.mskcc_0001.46
2014-11-21T15:05:26
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.
PS1
693
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.
bio.mskcc_0001.35
2015-01-21T03:05:03
ASPP2
CD72
2015-04-14T10:01:59
bel_pmid_1074_4722.15496
10744722
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).
p62
Ozawa
Upon CTD phosphorylation by TFIIH, RNA pol II dissociates from the initiation complex and leaves the promoter.
bio.chicago_2015.18156
2015-10-20T09:26:53
HER2
1E
B-Raf
V600E
B-Raf
Rushworth
1
1
-
bio.bmtr_0004.26
2015-01-06T06:25:29
Furthermore, this outcome was specific to monoubiquitination at position 147.
Ras
interrogative
Bonni
epidermal growth factor
DAT
cadherin
interrogative
bio.chicago_2015.19112
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).
2015-10-20T11:57:48
C-Raf
Cancer
cancer
ZNF217
EGFR
GEF
3.3
2015-01-14T06:53:00
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 .
bio.ras_0002.4
B
HCC827
-
-
ERK
BRAF
GAP-43
cyclin D2
bio.bel_0002.7
2015-02-05T10:59:48
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)
1B
bio.bmtr_0004.10
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).
2015-01-06T11:14:24
-
G12V
PP2A
threonine
EGFR
Ras
cyclin-dependent kinase
MDA-MB-468
2015-01-21T15:23:22
bio.mskcc_0001.54
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.
2015-01-06T10:36:40
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).
MEK
B-Raf
Ras
0.5
Erk
ASPP2
Mechanistically ASPP1 and ASPP2 bind RAS-GTP and potentiates RAS signalling to enhance p53 mediated apoptosis [2].
bio.bmtr_0005.4
2015-01-06T08:05:46
G466A
GTP
JAK
IL-3
alphaFtz-F1
cancer
Cancer
-
S750A
5
CD72
GDP
B-Raf
1
Ras
ASPP2
200
6
HER2
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.
a_pmid_2488_5690.37
24885690
2015-06-09T00:31:02
Ras
IGF-IR
bio.chicago_2015.19095
2015-10-20T11:08:30
P-TEFb may alter the role of Spt proteins either by phosphorylation of Pol II or Spt5 (Ivanov et al. 2000 ).
tyrosine
EGF
1
Cancer
cancer
OPCA
Serine
serine
671
-
30
lysine
117
bio.chicago_2015.17480
Axin mutants with C-terminal truncations lacked the ability to inhibit Lef-1 reporter activity, even though they bound GSK-3beta and beta-catenin.
2015-10-27T09:19:04
HER3
GSK-3beta
Sorafenib
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).
2015-01-19T22:53:44
bio.mskcc_0001.27
ERK
2E
GSK-3beta
S729A
HER2
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 ).
2015-10-21T13:03:50
transforming growth factor-b2
ERK12
5C
K-Ras
2000
MEK
DNA
DNA
15
ERK12
PI3KC2β
10640734
bel_pmid_1064_0734.39818
2015-04-09T05:13:20
However, the CD72 transfectants showed less increase in the intracellular Ca2+ concentration than the parent K46^mA cells did.
FGFR
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.
2015-06-18T07:16:08
15280923
GDP
bio.bmtr_0001.17
To corroborate this finding, we measure the activity of Ras by the GST-RBD pull-down assay.
2014-12-22T15:12:07
K-Ras
These results are consistent with a greater fraction of ubiquitinated K-Ras being in the GTP state (Fig. 2, A and B).
2014-12-22T14:32:40
bio.bmtr_0001.21
FoxO13A
beta-catenin
p42MAPK
2
2015-04-12T05:16:31
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),
bel_pmid_1069_9758.36926
CtBP2
V600E
PLX4032
K-Ras
MAPK
ERK2
-
T677A
GDP
C-Raf
p53
AP-2
extracellular signal-regulated kinase 1
AG
BRAF
threonine
669
bio.mskcc_0001.53
2015-01-21T14:48:03
Through mutational analysis, we find that feedback phosphorylation disrupts the abilities of B-Raf to bind activated Ras and to heterodimerize with C-Raf.
H-Ras
MDA-MB-231
2015-02-26T01:32:43
bmtr_0007.9
ASPP2 phosphorylation was rapid and transient as 3 hours after EGF stimulation phosphorylated ASPP2 was barely detectable.
Raf
401
threonine
PKI166
PKI166
1-2
5
cdc5 delta N
B-Raf
cetuximab
diacylglycerol
JM domain
ERK12
10666199
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
2015-04-09T08:03:06
EGFR
bio.chicago_2015.17165
2015-10-25T13:24:48
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.
Nakashima
SUM149
BRAF
-
15280923
pmid_1528_0923.66
2015-06-18T02:16:52
<sec-title level="1">RESULTS</sec-title>
C-Raf
bio.bmtr_0001.6
2014-12-09T22:40:15
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.chicago_2015.19083
How the interactions of filamin with actin and transmembrane proteins are regulated is largely unknown.
2015-10-20T06:32:06
bio.ras_0003.4
2015-01-19T05:25:54
His - ubiquitinated K-Ras was subsequently purified with anti - Flag resin .
Nagafuchi
Pin1
C-terminus
FoxO13A
30
Ras
Cooper
STAT
1
ES1
15280923
<sec-title level="2">Differential effect of PKI166 on ERK1/2 phosphorylation</sec-title>
2015-06-16T11:00:05
pmid_1528_0923.105
RKO
B-Raf
GI101A
12.453
2015-06-10T00:10:01
a_pmid_2488_5690.65
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>].
24885690
C-terminus
ERK2
ERBB3
ADP
ASPP2
B-Raf
bio.mskcc_0001.29
For these studies, FBm or S729A mutations were incorporated into a number of oncogenic B-Raf proteins that exhibit various levels of kinase activity.
2015-01-20T12:45:00
1A
Ras
BRAF_gene
BRAF
EGFR
2D
2015-01-07T01:51:47
bio.bmtr_0005.6
One of the most studied downstream pathways of RAS signalling is the Raf-MAPK pathway.
27
K-Ras
GTP
-
456
47
C-Raf
CTBP
AMR-PropBank-Frame
GTPase Activating Protein
B
SOCS3
8505C
Flag
CtBPs have also been described to negatively regulate transcriptional activity of the HER3 promoter in breast carcinoma cell lines ( 30 ) .
bio-exp_0001.11
2015-02-07T11:00:42
bio.chicago_2015.18690
Dephosphorylation of cyclin E by Cdc14 reverses the effects of the mitotic kinases and promotes cyclin E - Cdk2 binding to chromatin.
2015-10-21T13:45:39
7E
PKI166
Matrigel
ERBB3
K-Ras
JM domain
Cancer
cancer
2
serine
Axin
C-Raf
p53
signal regulatory protein alpha
MAPK
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.
2015-01-06T11:13:11
bio.bmtr_0004.9
C-terminus
Ras
guanine nucleotide-binding
2014-11-29T14:06:52
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.
bio.mskcc_0001.24
2015-04-09T06:47:05
bel_pmid_1064_8414.21216
10648414
Overexpression of mutant FGFR3 resulted in IL-6 independence, decreased apoptosis, and an enhanced proliferative response to IL-6.
Dl
DP
bcl-xL
BRAF
-
During cell morphogenesis and motility, cells undergo extensive remodeling of the actin cytoskeleton, a phenomenon that is mediated by various actin-binding proteins ( 1).
2015-10-22T11:30:05
bio.chicago_2015.18987
colorectal cancer
Colorectal_cancer
beta-catenin
2015-01-20T07:23:45
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 .
bio-kappa_0001.17
1
tyrosine
2015-01-20T06:22:13
bio-kappa_0001.14
Since the sites have been described alternatively as negative regulatory or activating , the significance of these dephosphorylation events for Raf activation is unclear .
M1
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).
bio.bmtr_0002.4
2014-12-14T20:53:57
Frodin
ERK12
IGF-IR
actin
B-Raf
Brummer
2
2015-06-10T00:16:49
24885690
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>].
ASPP2
PLX4032
EGF
HER3
A
50
2015-06-09T23:56:19
a_pmid_2488_5690.62
24885690
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.
bio.mskcc_0001.7
2014-11-05T22:08:42
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).
bmtr_0007.8
Phosphorylated endogenous ASPP2 was detected by the phospho-specific antibody 30 minutes after RAS stimulation (Figure 1D).
2015-02-26T01:28:20
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).
bio.mskcc_0001.16
2014-11-16T17:46:13
D594G
auxilin
Cdc14
4A
histidine
Chk2
PP2A
RNA
9
glycogen synthase kinase3 beta
RT
IL-3
Cds1
1999
STAT3
B-Raf
1997
750
serine
2+
MEK
HEK293T
GST-RBD
15280923
pmid_1528_0923.84
2015-06-21T09:11:05
As expected, cells expressing low levels of EGFR and HER2, GI101A, MDA-MB-435 showed least growth inhibition.
Ras
-
Dvl
2015-10-21T10:44:36
bio.chicago_2015.18510
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).
interrogative
Ras
52
sIL-6R
Id2
carcinoma
CtBP1
T cell factor lymphoid enhancer factor
bio.chicago_2015.17615
2015-10-27T14:48:22
For some of these transcription factors, the domain that interacts with Groucho is mapped to a short peptide motif.
750
serine
Under physiological conditions , the rate of GDP or GTP release from the G - domain is slow .
bio.ras_0001.5
2014-08-13T18:43:18
myosin
10777583
bel_pmid_1077_7583.7596
2015-04-16T05:24:23
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.
2015-06-15T13:48:11
MDA-MB-435 cells were significantly inhibited by U0126 alone, and the addition of PKI166 made no difference.
15280923
pmid_1528_0923.95
2015-10-21T14:50:57
bio.chicago_2015.19362
Ectopic Gem or Rad expression inhibits ROK-dependent functions such as formation of stress fibers and focal adhesions, neurite retraction, and Rho-dependent transformation.
p53
216
serine
216
serine
Ras
Raf
cyclin E
2
ILK
1
siRNA
Cancer
cancer
ERBB3
PKI166
Pin1
IL-6
FGF
EGFR
Yu
microtubule-associated protein 2
-
5
reporter gene
2+
PKI166
5
-
14-3-3
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 .
2015-01-20T02:34:12
C-Raf
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)
bio.bmtr_0003.1
2015-01-21T23:22:38
B-Raf
NGA
cysteine
76
Raf
cdc2
VEGFR-2
RBW-1
bio.mskcc_0001.44
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.
2014-11-21T13:03:30
S729A
ERK
All these demonstrate that ASPP2 is a novel substrate of MAPK and Ser827 of ASPP2 can be phosphorylated by RAS/MAPK pathway.
bmtr_0007.12
2015-02-26T02:12:13
Cdc25C
bio.chicago_2015.17801
GSK-3beta, glycogen synthase kinase 3beta; 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.
2015-10-28T01:30:03
2014-11-06T21:40:56
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
70
serine
BRAF
Ras
ERK
B-Raf
7A
HA-MEKK1-K1255M
Ras
24885690
a_pmid_2488_5690.40
2015-06-09T04:41:16
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>).
serine
1185
RASMAPK
threonine
753
threonine
bmtr_0006.4
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.
2015-02-25T09:44:18
2015-01-21T18:15:45
bio.bmtr_0002.20
These results demonstrate that EGFR T669 phosphorylation is necessary for MEK/ERK to suppress EGFR-mediated activation of ERBB3.
63
HER3
EGFR
V600E
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.
bio.chicago_2015.17089
2015-10-25T12:26:35
GSK3beta
bio.mskcc_0001.34
2015-01-21T02:29:01
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).
DNA
DNA
Dvl
2015-04-09T06:06:35
10640734
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.
bel_pmid_1064_0734.39828
BRAF
lysine
20
B-Raf
HER3
APC
2C
Cancer
cancer
15280923
2015-06-16T12:02:26
pmid_1528_0923.111
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>).
ITIM
STAT
reverse tetracycline controlled transactivator
pmid_1528_0923.77
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.
2015-06-19T00:53:23
B-Raf
-
Cancer
cancer
ATF CREB
1
lysine
147
693
MEKERK
NF-kB
2015-06-19T00:35:28
pmid_1528_0923.76
Thus, while the MDA-MB-231 cell line with highly activated ERK1/2 expressed a relatively high level of EGFR, other combinations occur.
15280923
B-Raf
ATM
ubiquitin
serine
750
bio.mskcc_0001.13
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.
2014-11-16T16:37:31
G12V
Cdc12
HER3
EGFR
IL-11
-
RAS
MEK
DNA
DNA
8
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.
24885690
2015-06-08T23:42:39
a_pmid_2488_5690.12
CD72
C-Raf
lysine
2014-12-18T17:04:39
bio.bmtr_0001.12
Interestingly, the ubiquitinated subfraction of wild-type K-Ras retained a significant amount of 32P-GTP.
beta-catenin
When compared to p38 SAPK, MAPK1 was clearly able to phosphorylate the ASPP2 fragment in vitro (Figure 1B, left and middle panels).
bio.bmtr_0005.11
2015-01-07T01:50:22
1
FoxO3A
1B
Ras
CtBP2
2005
32
Taken together, these results indicate that coligation with CD72 negatively regulates BCR-induced ERK activation and Ca2+ concentration in normal spleen B cells.
2015-04-09T06:29:32
10640734
bel_pmid_1064_0734.39832
CHO
DNA
DNA
CtBP2
2014-11-03T20:23:34
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.
ASPP2
2+
4
U0126
GTP
GEF
Ras17N
9
12
6
Tcf-4
Cancer
cancer
Furthermore, during early gastrulation, DLT normally colocalizes with CRB.
bio.chicago_2015.18798
2015-10-22T10:18:54
-
19
EGFR
GTP
serine
117
lysine
pmid_1528_0923.74
15280923
2015-06-18T08:10:43
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>).
5B
B-Raf
24885690
2015-06-09T23:18:51
a_pmid_2488_5690.55
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>].
ATP
BCR
2B
bio.chicago_2015.18974
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).
2015-10-22T11:18:19
Protein phosphatase 5
2
1
bio.bmtr_0004.14
As seen in Figure 5c, monoubiquitinated K-Ras is less sensitive than the unmodified protein to GAP-mediated GTP hydrolysis.
2015-01-06T13:00:57
26
GSK-3beta
p34Cdc2clb
GTP
axin
78
79
GAP
RKO
14-3-3
Dpp
tyrosine
SUM149
HER3
ERBB3
N-terminus
15280923
pmid_1528_0923.93
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>).
2015-06-21T13:04:23
1
calcium
Ras
S1C
NAC
ceramide
GTP
10640734
2015-04-09T04:44:25
bel_pmid_1064_0734.39812
Taken together, expression of CD72 most probably down-modu-lates phosphorylation of ERK induced by BCR signaling.
ERK
1.2
63
CNTF
bio.mskcc_0001.45
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.
2014-11-21T13:16:55
7B
2015-01-20T08:00:15
bio-kappa_0001.19
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 .
BHA
protein phosphatase 2A
MEKK1
DPP
Gly12
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.
2015-06-16T11:29:16
pmid_1528_0923.107
15280923
breast cancer
Breast_cancer
U0126
U0126
CtBP2
ERK
RBW-1
actin
PP2A
HER3
448
PKI166
B-Raf
bio.mskcc_0001.55
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.
2015-01-21T15:38:56
B-Raf
MDA-MB-231
Mek12
ERBB3
p90 ribosomal S6 kinase
B-Raf
bio.chicago_2015.19269
2015-10-21T02:29:26
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.
BRAF
K-Ras
1
Guanosine_diphosphate
GDP
Extradenticle
2014-12-14T20:21:31
bio.bmtr_0002.2
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.
We demonstrate that the RBD of PI3KC2β binds nucleotide-free Ras in vitro (Fig. 5).
2015-02-25T10:37:26
bmtr_0006.6
BRAF
MEK
2H
42
SRC-1
5b
1B
a_pmid_2488_5690.45
24885690
2015-06-09T05:27:35
Furthermore, all cells expressed <i>BRAF</i> protein at comparable levels (Figure <xref ref-type="fig" rid="F1">1</xref>C).
30
GAP
47
Ras
Ha-Ras
PAF
-
orthophosphate
2015-10-21T09:55:48
bio.chicago_2015.18258
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.
EGFR
Inhibition of GSK-3beta-dependent phosphorylation of Axin by Dvl.
2015-10-28T05:17:13
bio.chicago_2015.18091
Turke et al. “MEK inhibition leads to PI3K/AKT activation by relieving a negative feedback on ERBB receptors” (PMC3515079)
bio.bmtr_0002.1
2014-12-10T12:17:16
GTPase
22
-
2014-08-13T17:11:08
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
CRE
Axin
GATA-1
-
5B
-
BRAF
Pol II
6
5
serine
C-Raf
bio.bmtr_0005.14
2015-01-07T02:59:19
Each eluted fraction was measured for its radioactivity content (Figure 1B, right panel).
Ras
PMC3537887
p42ERK2
clathrin
Erk12
PI3KC2β
22
RAFTK
4
-
alpha-catenin
beta-catenin
Ras
GAGA factor
Ras
U0126
CBP
HER2
We thus tested whether RAS activation may regulate ASPP2 phosphorylation.
bio.bmtr_0005.9
2015-01-07T01:10:14
B-Raf
GDP
RKO
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.
bio.bel_0002.2
2014-09-29T14:54:34
ERK
PIK3CA
GAP
5D
3B
serine
2
carcinoma
interrogative
IL-8
PLX4032
bio-exp_0001.7
Serial deletions identified a minimal HER3 promoter retaining transcriptional response to vemurafenib and AZD6244 , which was located between -401 and -42 bp ( Fig. 5C ) .
2015-02-07T10:25:54
B-Raf
5.0
B-Raf
luciferase
bel_pmid_1064_0734.39814
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).
2015-04-09T04:55:18
10640734
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.
2015-10-21T01:50:29
bio.chicago_2015.19251
6A
interrogative
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 .
2014-08-13T16:12:45
EGFR
Raf
alphaFtz-F1
0.001
AMR-EntityType
AMR-Term
mRNA
S5A
Because the mutations in PS1 apparently inhibit transcriptional activity of beta-catenin downstream of GSK 3beta, we hypothesized that PS1 may be interacting with the binding partner of beta-catenin, namely hTcf-4.
bio.chicago_2015.17718
2015-10-28T00:35:29
serine
395
A
AZD6244
MEK
threonine
PKI166
GST-RBD
43
serine
LEF-1
pFopflash plasmid
--
5
serine
G12V
S729A
UO126
293T
interrogative
chromatin
753
threonine
MAPK
-
M1
caspase 3
B-Raf
M1
HER3
2
2
30
70
bio.bmtr_0002.12
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.
2014-12-15T15:37:12
AKT
Lef-1
5B
ERK2
T669A
1
bio.mskcc_0001.36
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).
2015-01-21T05:10:00
threonine
ERBB3
filamin
4A
-
ASPP2
MAP2
1
B-Raf
hTcf-4
MDA-MB-231
-
15280923
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>.
2015-06-21T06:17:25
pmid_1528_0923.81
10842184
2015-04-16T19:28:31
\"Negative regulation of growth hormone receptor/JAK2 signaling by signal regulatory protein alpha.\"
bel_pmid_1084_2184.19138
B-Raf
Passage 1-2 (Discussion/Conclusion)
2015-01-07T05:01:25
bio.bmtr_0005.18
729
serine
S3
CD72
CTn repeat
HER2
10640734
2015-04-09T05:35:11
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).
bel_pmid_1064_0734.39824
Notch
2
Cancer
cancer
-
5
Lef-1
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>].
a_pmid_2488_5690.35
2015-06-09T00:20:02
24885690
threonine
669
tetratricopeptide domain
bio.bmtr_0001.9
2014-12-09T22:57:04
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.
155
bio.bmtr_0003.7
2015-01-25T14:48:37
RAF or MEK inhibitors induced luciferase activity of a HER3 promoter construct spanning ~ 1 kb upstream of the transcriptional start site in 8505C cells.
ERK
2014-09-29T14:32:03
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.
bio.bel_0002.1
cyclin D1
SUM149
68
threonine
CtBP1
ERK
4
DNA
DNA
glucose
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).
2015-01-25T17:19:05
bio.bmtr_0003.21
MDA-MB-231
Ras
RasGAP
bel_pmid_1072_9607.19486
Activation of tyrosine kinases Fyn and Lyn, but not Lck, also occurred within 2 min after PAF stimulation in the cells
10729607
2015-04-13T12:30:20
2015-06-16T12:21:26
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
pmid_1528_0923.112
threonine
2
PI3
B-Raf
2014-12-17T01:40:22
bio.bmtr_0002.11
In contrast, the EGFR T669A mutant increased both basal EGFR and ERBB3 tyrosine phosphorylation that was not augmented by MEK inhibition.
T669A
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).
24885690
a_pmid_2488_5690.59
2015-06-09T23:38:16
U0126
bio.chicago_2015.18911
However, caldesmon together with TM completely inhibits actin binding of human fascin.
2015-10-22T10:26:00
bio.chicago_2015.18747
Regulation of Dpp Targets by brinker.
2015-10-22T09:22:43
0.5
2015-01-25T14:19:38
Similar results were found following treatment with the MEK inhibitor AZD6244 (not shown).
bio.bmtr_0003.5
ADH1
31
-
753
threonine
17
PLD
a_pmid_2488_5690.42
2015-06-09T05:02:53
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
14-3-3
2
11
10
PKI166
K-Ras
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.
2015-10-20T15:07:36
bio.chicago_2015.19160
MEK
AKT
19
PKI166
-
BCR
STAT5
Ras
gp130
K-Ras K-Ras4B
-
32
Ras
B56alpha
The ability to form H-DNA cannot substitute for GAGA factor binding to the ( CT)n sequence.
bio.chicago_2015.17831
2015-10-28T02:37:03
a_pmid_2488_5690.41
2015-06-09T04:51:08
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.
24885690
ATP
interrogative
lysine
104
750
serine
0.5
Takeichi
B-Raf
2A
SH3PX1
LIM B
EGFR
EGFR
-
HER2
stauro
PP2A
Axin
2B
GDP
14-3-3
14-3-3_protein
10729607
2015-04-13T14:03:47
transforming growth factor-b2 (TGF-b2) was shown to upregulate the transcription rate of PAFR transcript 1 in Ramos human lymphoblastoid cells
bel_pmid_1072_9607.31242
NF-kB
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 .
bio-kappa_0001.12
2015-01-20T05:30:27
gamma-tubulin
Raf
EGFR
trypsin
2014-11-03T20:34:01
bio.mskcc_0001.6
Strikingly, the Raf proteins themselves are also substrates of activated ERK.
B-Raf
54
EGFR
PMC3441633
C-RAF
Notch
2015-10-21T13:09:51
DLT Interacts with CRB and NRX IV
bio.chicago_2015.18617
bio.bmtr_0004.15
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.
2015-01-06T13:05:57
EGFR
vemurafenib
serine
729
GTP
JAK2
RKO
serine
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 .
2015-01-20T09:16:31
G4 box
ERK12
beta-catenin
-
Mek
Ras
Dox
bio.bmtr_0005.19
We and others have recently shown that ASPP2 can potentiate RAS signaling by binding directly via the ASPP2 N-terminus [2,6].
2015-01-07T05:12:17
PKI166
Ras
2014-11-16T16:54:17
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.
bio.mskcc_0001.14
H-Ras
AZD6244
-
Notch
Peltenburg
824
832
ASPP1
HER2
p53
-
p53
FoxO
Cancer
cancer
72
lysine
117
p38 SAPK
Ras
U1026
ERK1
Struhl
progesterone receptor
flow cytometry
Chk2
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.
2015-01-21T14:42:13
E1A
bio-exp_0001.14
Finally , CtBP1 and CtBP2 chromatin immunoprecipitation assays showed decreased binding to the HER3 promoter after treatment with PLX4032 ( Fig. 5F ) .
2015-02-07T11:19:08
Chk2
151
serine
-
JM domain
hairy
2
27
Michaloglou
SH2 domain
FGFs activate the endogenous FGFRs leading to the formation of a Grb2/FRS2/Shp2 complex and activation of MAP kinase.
2015-04-16T14:12:34
10851026
bel_pmid_1085_1026.6144
CtBP1
PKI166 inhibited ERK1/2 phosphorylation in SUM149 cells, as did U0126 alone, and further inhibition by the combination of drugs was barely discernible.
2015-06-16T11:44:35
pmid_1528_0923.108
15280923
MAPK
EGFR
ASPP2
GTP
NSCLC
U2AF35
p53
6A
Sorafenib is a potent TKI of VEGFR-2, VEGFR-3, B-RAF, and PDGFR-B
2015-01-23T03:54:56
bio.bel_0002.9
vMLC-1
Raf
C-Raf
Cdc25C
Grb2
1D
proline
Raf
ZFN217
bio-kappa_0001.13
In addition to promoting C-Raf activation , PP2A is also able to dephosphorylate Erk - dependent sites on C-Raf .
2015-01-20T06:02:25
Rad
IGF-I
K-Ras
bio.ras_0001.10
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 ) .
2014-08-13T21:50:34
B-RAF
B-Raf
actin
K-Ras
FoxO
Guichet
extracellular signal-related kinase
13
15
ERK
1996
PKC betaII
C-Raf
Cot
6A
90
EGFR
microsattelite instability
CCT
RafMekErk
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.
bio.bmtr_0004.17
2015-01-06T13:19:56
6C
GDP
Guanosine_diphosphate
5A
ERK12
This switch - ON process involves the exchange of GDP for GTP , and is , at least in principle , reversible .
2015-01-20T08:17:10
bio-kappa_0001.22
PI3KAKT
C-Raf
Rb
HER3
14-3-3
STAT
cancer
Cancer
ERBB
G466A
5
Cdc25C
Ras
H-Ras
-
401
threonine
Raf
HER3
ERBB3
PS1
1
STAT3
5E
4
-
E2F
GAGA factor
B
3
hKSR-2
V600E
1997
5D
IL-6
372
368
bio.chicago_2015.17550
2015-10-27T14:46:47
In vivo binding of GSK-3beta with Axin or beta-catenin.
Cancer
cancer
B-Raf
MEK
GFP
C-terminus
2015-02-26T01:00:24
bmtr_0007.4
To test the efficacy of the purified phospho-specific
ERK12
RASRafMAPK
Ftz
PI3KAKT
DNA
DNA
1A
2H
Myc
8
doxycycline
IGF-IR
B-Raf
B-Raf
8505C
-
Ras
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.
bio.bmtr_0003.17
2015-01-25T16:51:39
--
GEF
Cancer
cancer
Mac-1
CD72
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.
2014-11-22T19:21:02
bio.mskcc_0001.50
3A
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 .
2014-09-16T11:13:45
8
2015-01-28T02:52:22
bio-exp_0001.8
This region does not contain any predicted FoxO binding sites .
11
27
imperative
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.
2015-01-23T14:45:30
bio.bmtr_0003.3
PKC
B-Raf
-
adenomatous polyposis coli
Bcl2
a_pmid_2488_5690.36
24885690
2015-06-09T00:25:38
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>].
1B
1B
threonine
669
-
Raf
28
RAF265
10677502
bel_pmid_1067_7502.3614
2015-04-09T08:22:18
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
ERK12
401
threonine
-
PKI166
5
HER2
GAP
ubiquitin
0.1
Axin
PSP
10
9
1-2
homeodomain
2015-06-09T00:01:34
a_pmid_2488_5690.33
24885690
<i>BRAF</i> targeting in RKO
Cancer
cancer
CD72
beta-galactosidase
RKO
K-Ras
677
threonine
AZD6244
B-Raf
SUM149
Sos
T401A
Ras
shRNA
10
Cancer
cancer
TcfLEF
Murre
IL-11
B-Raf
dabrafenib
30
retinoic acid
-
growth hormone receptor
breast cancer
Breast_cancer
Erk
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.
bio.mskcc_0001.38
2015-01-21T09:11:56
-
89
6A
-401
bel_pmid_1072_9607.19488
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
2015-04-13T12:41:31
CTBP2
CK2
bio.chicago_2015.18130
2015-10-20T03:27:20
Hemin treatment caused no reduction in cellular glutathione concentrations, indicating that the increased TRX expression was not due to oxidative stress.
-
ERK2
Lukas
lysine
170
Figure 1C shows that the phosphospecific antibody is specific for the ASPP2 fragment phosphorylated in vitro by MAPK.
bmtr_0007.6
2015-02-26T01:02:48
SHP2
V600E
EGFR
K-Ras
3F
tyrosine
EGFR
-
HRG
HER3
ATM
GTP
bio.chicago_2015.18031
This observation suggested that the 60-residue linker region may assist Ldb binding by LIM B in the 1m construct.
2015-10-28T03:57:48
2
HER2
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.bmtr_0003.13
2015-01-25T16:25:03
actin
22
C-Raf
2+
PI3KC2β
ATM
C-Raf
C-Raf
-
PKI166
AKT
Ras
cyclin D1
Ldb
Ras
green fluorescence protein
2
GTP
MDA-MB-435
PKA
ERK2
BRAF
MAP2K2
MEK2
32
EGFR
G469A
2015-01-23T02:19:50
In addition, introduction of B-Raf enhances and sustains integrin-mediated activation of ERK in wild-type primary fibroblasts
bio.bel_0002.5
60
4
Mek
SUM149
HEK293T
2014-11-28T18:08:23
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).
bio.mskcc_0001.23
beta-catenin
hCdc14 phosphatase
Mlodzik
lamin B
serine
GST-RBD
interrogative
-
1A
3
Raf
HER3
Cancer
cancer
interrogative
Ras
K-Ras
Cds1
NF1
cytokine
HER2
B-Raf
4B
paclitaxel
C-Raf
bio.bel_0002.4
2015-02-05T10:13:38
The homologous site on B-Raf, S445, is constitutively phosphorylated, accounting for the higher basal activity of B-Raf.
K-Ras
GTP
B-Raf
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
2014-12-22T15:30:38
Cds1
Venable
14-3-3
NIH 3T3
Ras
ERK12
beta-TrCP
3
EGFR
APC
ERK
5
2
interrogative
ISWI
Urano
S1B
698
PA
C-terminus
Breast_cancer
breast cancer
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.
2015-06-16T11:55:33
15280923
pmid_1528_0923.110
HER3
Zwartkruis
37
Axin
PP2A
Rimm
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).
2015-01-21T16:49:26
bio.bmtr_0002.16
S1D
AF6
27
fascin
Finally, CtBP1 and CtBP2 chromatin immunoprecipitation assays showed decreased binding to the HER3 promoter after treatment with PLX4032 (Fig. 5F).
bio.bmtr_0003.15
2015-01-25T16:39:57
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
2015-10-28T04:11:05
CRB
B-Raf
PI3K
ERK1
threonine
30
28
EGF
Ras
EGFR
ERK12
ubiquitin
DLT
MAPK
B9
STAT3
K-Ras
Ras
bio.bmtr_0002.21
This supports the hypothesis that a dominant ERK feedback on ERBB3/PI3K/AKT is mediated though phosphorylation of T669 on EGFR (or T677 HER2).
2015-01-21T18:24:17
I
DBA2 mouse
-
fascin
serine
446
HER3
SKBR3
MAPK
PKC
p44ERK1
-
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)
2015-04-16T13:27:35
10880513
bel_pmid_1088_0513.23686
EGFR
Hox
catenin
2
PAF
BRAF
bio.bmtr_0004.24
The analysis revealed that monoubiquitination abrogates GAP-mediated GTP hydrolysis.
2015-01-06T03:38:45
2015-06-09T09:59:07
24885690
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).
a_pmid_2488_5690.49
293T
Ha-Ras
3A
Smith
U0126
66
NF-kB
G-domain
PKI166
Hsc70
AZD6244
RAS
K-Ras
Gammeltoft
RalGDS
-
5B
24
23
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>].
2015-06-09T00:10:23
24885690
a_pmid_2488_5690.34
focal adhesion kinase
5E
LEF TCF
ERBB3
-
As expected, addition of AZD6244 failed to further augment ERBB3 and AKT phosphorylation in cells expressing the 669A mutant.
bio.bmtr_0002.19
2015-01-21T17:56:39
111
GAP
1
bio.bmtr_0003.2
We next examined the mechanisms accounting for the increase in HER3 by MAPK pathway inhibitors in BRAF mutant thyroid cell lines.
2015-01-23T13:38:34
Dpp
serine
AZD6244
bio.ras_0002.1
Activated Ras controls diverse signaling pathways that ultimately determine Ras - induced cellular responses such as cell proliferation , survival , differentiation and motility .
2015-01-13T21:00:03
lysine
147
Kamps
Wnt
HER2
19
6A
CKI did not phosphorylate GSK3beta, B56alpha, or beta-TrCP.
bio.chicago_2015.17707
2015-10-27T15:29:36
ERBB3
1995
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.
bio.chicago_2015.17666
2015-10-27T15:29:09
sorafenib
GTP
Gly13
GAP
SUM149
827
serine
Mek
1B
Chk2
50
2015-06-09T10:31:52
24885690
a_pmid_2488_5690.54
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>].
5D
vemurafenib
-
Ras
DNA
DNA
RA
729
serine
H-Ras
U0126
B-Raf
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).
2015-01-25T17:00:21
JNK
EGFR
Hulsken
caldesmon
3
ASPP2
3F
1
2015-06-18T03:20:56
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
15280923
Ksr
GTPase
K-Ras
HER3
PKI166
GDP
PLX4032
HER2
33
CD72
Pol II
lysine
170
alkaline phosphatase
Ras
Notch
CD72
24
bio.bmtr_0005.23
2015-01-07T05:40:37
Additionally, RAS/Raf/MAPK pathway activation stabilizes ASPP2 protein, although the underlying mechanism remains to be investigated.
C-Raf
ubiquitin
Breast_cancer
breast cancer
Axin
Ras
60
2A
ASPP2
-
DNA
DNA
cyclin E
PI3KAKT
O'Connor
TPO
2
U0126
MDA-MB-435
GDP
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 .
2014-08-13T18:57:28
bio.ras_0001.7
77
cysteine
RAF
827
ABP
Phelan
TM
14-3-3
GST-RBD
Ras
EGFR
N-terminus
STAT3
MAPK
5.0
PKC
H-ras
Spt
SUM149
bel_pmid_1074_4722.15494
10744722
2015-04-14T09:48:01
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).
G1
serine
BRAF
threonine
serine
4
IkB
66
ubiquitin
oncwt-
Sur-8
MAPK
Gem
2015-01-19T07:59:53
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
6B
G5 box
1B
C-terminus
K-Ras
--
MAPK
2F
SKBR3
K-Ras
2
PKI166
MEK
B-Raf
GTP
HER3
ERK
C-terminus
PKI166
PI3-Kinase
247
EGFP
7
1
beta-catenin
IL-6
B-Raf
lysine
147
cyclin D1
293T
32
ERK12
DMSO
29
ASPP2
JAK2
-
CD72
MAPK
Raf
Bcl2
2
PKI166
PKC betaII
-
1A
ERK-1
Mek
GFAP
-
Ras
ASPP
PMID15280923
27
16
28
2A
ICAT
20
2C
Sca
PIK3CA
MDA-MB-468
Ras
reverse transcriptase
ERK
3E
10
PKC
MDA-MB-468
G-domain
cdc25C
IL-6
13
ERK1
ERK
cdk4
G466A
PSP
tyrosine
DLT
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).
2015-10-27T15:29:27
tyrosine
2B
MAP kinase
1C
RafMEKERK
GEF
Bray
NRX IV
T669A
S151A
RAF
1
threonine
1179
CD72
IGF-I
Iro-C
5B
Ras
RKO
-
NF1
ERK
-
Chk2
RKO
Flag
-
EGFR
Ras
Raf
Erk-2
GFAP
151
serine
U0126
RasGEF
cancer
Cancer
5
Ras
C-Raf
8A
RafMekErk
lysine
147
bio.mskcc_0001.10
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)
2014-11-06T22:59:41
1
phosphoinositide 3-kinase AKT
GAP
−−
CD18
CD72
2
MEK2
beta-catenin
Mitogen-activated_protein_kinase_kinase
MEK
tyrosine kinase Lyn
ubiquitin
Ftz
alanine
C-Raf
C-Raf
P-TEFb
10
Ras
-
B-Raf
HRASV12
a-tocopherol
ERK12
B-Raf
1A
A-T
-
IL-6
tyrosine
MAP
RBO-1
B-Raf
-
Raf
1C
1
2014-08-13T19:05:56
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
RBOW
Breast_cancer
breast cancer
interrogative
phenylmethylsulfonyl fluoride
4B
PS1
MAPK1
GAP
Jak1
cancer
Cancer
1D
Ras
10000
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 ) .
bio.ras_0003.7
2015-01-19T07:05:34
HER2
GAP
PLD
K46^mA
K-Ras
2015-10-22T11:34:00
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
bio.chicago_2015.19008
Ras
GST
Ras
bio.bmtr_0005.22
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).
2015-01-07T05:10:22
SHP2
Mek12
T35
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).
2014-11-09T19:29:37
bio.mskcc_0001.11
8
10
PBS
PKI166
FoxO3A
B-Raf
7
SHP2
2A
Colorectal_cancer
colon cancer
ERK
PP5
TGF-beta
ERK-2
beta-tubulin
serine
3
-
7
ERBB
p19INK4D
HER3
CtBP
T753A
TBP
CKI
B
Fanto
ROK
Delta
Shc
p53
Yamazaki
Raf
RAF_kinase
K-Ras
ERBB3
Ras
AZD6244
Pin1
1
2
C-RAF
lysine
117
HER3
MEK1
ERK12
-
1B
ERK12
Cancer
cancer
Ivanov
PDGF
PMSF
72
Pin1
C-Raf
H-DNA
81
alanine
216
serine
1A
p38 SAPK
Erk
SKBR3
1
GAP
21
18
actin
C-Raf
B-Raf
Pin1
protein kinase A
C-Raf
BCR
C-Raf
27
2+
4
2
p53
GDP
15280923
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>).
2015-06-16T12:35:01
pmid_1528_0923.113
senescence-associated β-galactosidase
PP2A
MDA-MB-231
HER3
pTopflash plasmid
8505C
B
ERK
227
p53
NF-kB
PUMA
Erk12
ERK
fcp1
b-ZIP
3
eosinophil
PAF
MEK
Ras
-
Lck
tyrosine
293T
Tolloid
CRB
C-Raf
ASPP1
GSK-3
1998
6B
NF1
1m
Par6b
2015-10-28T03:20:35
bio.chicago_2015.18003
LiCl Activates a Prosurvival Pathway through GSK-3beta 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.
ERK
EGFR
MDA-MB-231
S1D
FBS
12V
MDA-MB-435
MEK
alpha-tubulin
2B
GTP
RASRafMAPK
S729A
rtTA
6
32
RBO-2
3D
Chk2
8
32
C-Raf
Ras
glutathione
CD11b
Cdk2
tyrosine
GFAP
MDA-MB-231
Sp-1
GTP
FGFR3
ATF-1
ATM
AMR-Concept
EGFR
12
253
-
GTP
HEK293
2H
FRS2
-
beta-catenin
B-Raf
8.5
S729A
ERK
Mek
GTP
GAP
32
CtBP1
1
B-Raf
NURF
ERK12
5
C-Raf
HEK293T
1999
746
Flag
SUM149
CHO-KI
GDP
GNBP
PI3K-C2beta
peroxiredoxin
-
ERK
14-3-3
1
-
histidine
RKO
BRAF
1
DPP
GSK-3beta
RASMAPK
K-Ras
PKC
RKO
Ras
B-Raf
mitomycin C
Grb2
HER2
Ras
GTP
AMR-PropBank-Role
Pin1
GTP
Pin1
trypsin
MEK
5E
6
1A
Pin1
1996
ERK
1-1
CtBP
ERK12
Ras
Erk12
STAT5
PDGFR-B
neurite
JAK1
EGFR
1998
EGFR
histidine
beta-catenin
MEK
GTP
1
1994
5-fluorouracil
okadaic acid
BCR
HER2
B-Raf
PKI166
28
30
LiCl
SKBR3
U0126
Montero-Conde
cyclin D3
propidium iodide
Huang
Dl then activates Notch (N) in the R4 precursor ( Cooper and Bray, 1999; Fanto and Mlodzik, 1999; Tomlinson and Struhl, 1999).
bio.chicago_2015.17347
2015-10-27T08:45:34
hKSR-2
Ras
p44MAPK
MDA-MB-468
HER3
BRAF
serine
histidine
TGF-b2
HER2
GSK-3beta
tyrosine
Raf-MAPK
EGFR
MDA-MB-435
ERBB3
1C
6C
Grb2
GAP
beta-catenin
1987
-
5b
93
MEK
p27KIP1
Dex
ATM
CTBP1
K46^mk
2G
MEK
MEK
actinin
ASPP2
PKI166
PAF receptor
dpc
PR
Grb2
histidine
MEK
Rheb
MKK1
Rheb
HER3
beta-catenin
Following ligand binding , Sos is brought from the cytoplasm to the activated receptor in a phosphotyrosine - dependent manner through adapter proteins such as Grb2 .
2015-01-20T07:43:07
bio-kappa_0001.18
B-Raf
MDA-MB-468
C3G
ATM
HER3
BCR
PAFR transcript 1
threonine
3D
2+
827
GST
S729A
H2O2
PKC
58
59
19
GTP
SUM149
tyrosine
BRAF
De Cesare
MDA-MB-468
PLX4032
Flag
HER2
CTn sequence
CKI
PP2A
C-Raf
C-Raf
SRC-1
GAP
IL-2
BRAF
DMEM
IGF-I
RAS
CHO-KI
2002
B-Raf
RNA
STAT