A database built with INDRA combining content from numerous readers and databases. This page allows you to curate the loaded statements. For more information please see the manual.

IndraLab

Statements

databases
phosphosite cbn pc11 biopax bel_lc signor biogrid tas lincs_drug hprd trrust | geneways tees isi trips rlimsp medscan sparser reach
reading

BRAF activates ERK. 10 / 376
| 1 64 292
reach
"Mutations in the KRAS and BRAF oncogenes activates the MAPK pathway, cell proliferation, and cell survival, thereby promoting invasion and metastasis [XREF_BIBR]."
reach
"Inhibition of B-Raf or MEK in B-Raf-mutant cancer cells suppresses ERK activation accompanied by downregulation of DR5 expression and decreased cell sensitivity to DR5 activation induced apoptosis, as we recently demonstrated XREF_BIBR."
reach
"Substitution of BRAF lysine 578 with arginine (K578R) inhibited BRAF mediated ERK activation."
reach
"Mutant-v-raf murine sarcoma viral oncogene homolog B1 (BRAF) is found in approximately 50% of melanomas 1 and induces constituent MEK and extracellular signal regulated kinase (ERK) signaling in melanoma cells."
sparser
"Although practically all melanomas bearing mutated BRAF present activation of MAPK and only a small fraction of the nevi follows the same pattern, the existence of MAPK-independent cellular effects [MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
reach
"The study suggests that multiple factors contribute to the transition and maintenance of the IDTC state and from these observations it is tempting to speculate that the burden of signaling is distributed between multiple pathways unlike the parental BRAF mutant cells, which seem to be primarily dependent on BRAF driven ERK signaling."
reach
"The complexity of BRAF-CRAF cross-talk was previously highlighted by Heidorn et al., who showed that although they effectively block BRAF mediated ERK signaling, BRAF inhibitors can induce ERK signaling through activation of CRAF in mutant RAS bearing melanoma 9."
reach
"This is expected as BRAF activates the MAPK pathway, and the association is only found in skin, where BRAF inhibitors have proven successful in the clinic, specifically by blocking the mutant form BRAF V600E 16."
sparser
"Activated B-Raf phosphorylates and activates ERK 1/2, which in turn phosphorylates several substrates including members of the 90 kDa ribosomal S6 kinase (RS6K) ( xref , xref )."
reach
"RAF265 inhibited BRAF mediated downstream activation of ERK, which was conceived as the major underlying mechanism for the growth inhibition of human colorectal carcinoma in an orthotopic transplant tumor model."
BRAF-V600E activates ERK. 9 / 129
| 126
reach
"The BRAF gene, a viral oncogene homolog that encodes a kinase involved in the RAS/RAF/MEK/ERK pathway, is mutated in up to 70% of melanomas, with mutations such as BRAF V600E causing constitutive MEK and ERK activation."
reach
"The most prevalent melanoma mutation is BRAF (V600E), which constitutively activates downstream MAPK signaling."
reach
"Following the down regulation of ALK RES, a decrease in pERK was detected in presence of PLX4032 while no change was observed in absence of the drug, which was expected since BRAF V600E is not inhibited and activates the ERK1/2 pathway."
reach
"One possible explanation is that MAPK activation by BRAF V600E may also disturb the equilibrium of PI3K pathway, as cross-talk may occur between PI3K and MAPK at multiple levels [XREF_BIBR]."
reach
"Finally, BRAF V600E overexpression activated the MEK and ERK signal pathway in B-CPAP and TPC-1 cells."
reach
"Our data show that V600E Braf can drive Erk and Wnt pathway activation and the formation of hyperplastic crypts that subsequently remain dormant for prolonged periods due to the upregulation of p16 INK4a."
reach
"Co-inhibition of BRAF V600E and MEK prevents recovery of MAPK signaling."
reach
"The BRAF V600E (BRAF+) mutation activates the MAPK and ERK pathway and may confer an aggressive phenotype in papillary thyroid cancer (PTC)."
reach
"While activation of ERK1/2 by BRAF V600E in melanoma cells inhibits Wnt and beta-catenin signaling XREF_BIBR, forced expression of BRAF V600E enhances Wnt and beta-catenin signaling in normal melanocytes (XREF_FIG)."
Mutated BRAF activates ERK. 10 / 91
| 91
reach
"However co-expression of class 3 BRAF mutants with wild-type CRAF in these cells induced ERK signalling (XREF_FIG)."
reach
"Most papillary thyroid cancer expresses RET and PTC or BRAF mutants, which activate the MAPK pathway of MEK-ERK."
reach
"Mutant BRAF kinase can be inhibited by the use of selective BRAF inhibitors (such as vemurafenib and dabrafenib), thereby blocking the constitutive activation of the MAPK pathway XREF_BIBR - XREF_BIBR."
reach
"Yamashita et al [XREF_BIBR] suggested that mutations of BRAF and RAS genes and rearrangement of RET and PET gene could activate MAPK pathway, which in turn activate NF-kappaB pathway and increase the progression and invasiveness of PTCs."
reach
"In HEK293T cells, Trametinib modestly decreased ERK activity induced by BRAF mutations conferring elevated kinase activity while strongly inhibited kinase impaired BRAF and CRAF induced ERK activation."
reach
"However inhibitor bound mutant BRAF can still dimerize with uninhibited CRAF to activate MAPK, consequently leading to proliferation and tumor progression, XREF_BIBR, XREF_BIBR highlighting the importance of additional downstream inhibitors."
reach
"These differences suggest that although both BRAF mutation and the RET and PTC1 rearrangement are able to activate the MEK and ERK signal transduction pathway, other pathways not affected by PD0325901 may be involved in PTC cells with the RET and PTC rearrangements."
reach
"Furthermore, certain BRAF V600E -mutant melanomas and colorectal carcinomas appear to develop a dependence or ' addiction ' to Bim repression, since inhibition of mutant BRAF driven ERK1/2 signalling results in Bim accumulation and Bim mediated apoptosis."
reach
"Importantly, administration of targeted therapy inhibiting mutant BRAF to BRAF wild-type patients has been shown not only to have absence of benefit, but can also cause a growth advantage in those tumor cells by paradoxically stimulating the MAPK pathway."
reach
"Mutant BRAF led to deregulated activation of downstream MEK and ERK effectors in melanoma patients."
BRAF-L505H activates ERK. 5 / 5
| 5
reach
"Moreover, BRAF L505H mutant can activate MAPK signaling, but has a smaller activating and oncogenic potential than the prevalent BRAF V600E mutation."
reach
"The BRAF L505H mutation is sufficient to activate MAPK signaling in cells and in in vitro kinase assays, albeit to a lesser extent than the BRAF V600E mutation (XREF_FIG)."
reach
"As expected from our data in melanoma, MAPK activation by BRAF L505H is resistant to PLX4032 but sensitive to MEK inhibitors."
reach
"As expected from our data in melanoma, MAPK activation by BRAF L505H is resistant to PLX4032 but sensitive to MEK inhibitors (XREF_FIG)."
reach
"The BRAF L505H mutation is sufficient to activate MAPK signaling in cells and in in vitro kinase assays, albeit to a lesser extent than the BRAF V600E mutation."
BRAF bound to RAF1 activates ERK. 5 / 5
| 5
reach
"A recent study reported that a subset of MEK inhibitors that are inactive in RAS-mutant cancers (AZD6244, GDC-0973) promotes BRAF and CRAF heterodimer formation allowing feedback activation of MEK and ERK, whereas RAS active MEK inhibitors (GDC-0623, G-573) stabilize a nonproductive RAF and MEK complex preventing MEK feedback activation."
reach
"Interestingly, this version of BRAF still bound to CRAF, indicating that it is not drug binding per se, but inhibition of BRAF activity, that drives BRAF binding to CRAF and paradoxical activation of MEK and ERK."
reach
"Biochemical analysis further revealed that addition of RGS to HeLa cells inhibits the heterodimerization of c-Raf and B-Raf, thereby inhibiting the activation of MEK and ERK pathway."
reach
"Targeting MEK downstream of BRAF and CRAF heterodimers using PD0325901 subsequent to RAF inhibitor treatment reduced ERK1/2 rebound and simultaneous treatment of tumor xenografts with both RAF and MEK inhibitors led to more pronounced tumor growth inhibition than either treatment alone."
reach
"A novel mechanism for response was discovered whereby high expression level of CAV-1 at the plasma membrane disrupts the BRaf and CRaf heterodimer and thus inhibits the activation of MAPK pathway during dasatinib treatment."
BRAF-Y472C activates ERK. 4 / 4
| 4
reach
"As before, the expression of Y472C BRAF led to the activation of ERK and increased sensitivity to dasatinib."
reach
"Y472C BRAF and G466V BRAF both activated MEK and ERK to levels at or above those observed after transfection with wt BRAF."
reach
"As with previously characterized kinase inactivating BRAF mutations, Y472C BRAF expression led to CRAF, MEK, and ERK activation."
reach
"Lung Cancer Cells Expressing Y472C BRAF Express Activated MEK, ERK, and CRAF."
BRAF activates phosphorylated ERK. 3 / 3
| 3
reach
"Next, we analyzed the protein expression of MAPK and ERK signaling which regulates cell proliferation and differentiation, and we observed that FAM83F increased BRAF levels and induced the activation of pERK (XREF_FIG)."
reach
"Intriguingly, RKO had only partial inhibition of pERK at 1microM (60% by densitometry); however dual PI3K and BRAF inhibition reduced pERK further (90% inhibition)."
reach
"Disruption of BRAF dimerization with the R509H mutation almost completely abolishes induction of p-MEK and p-ERK by class 3 BRAF mutants, but not by dimer independent BRAF (V600E) (XREF_FIG and XREF_FIG)."
BRAF-V600E activates phosphorylated ERK. 3 / 3
| 3
reach
"Transient expression of BRAF V600E for 48h also increased p-ERK accompanied by increased global histone acetylation, while expression of WT-BRAF did not have such effects (XREF_FIG, middle panel), confirming the specific effect of BRAF V600E on histone acetylation."
reach
"The BRAF V600E mutation, which approaches 50% in human melanomas, constitutively activates pERK and contributes to disease progression."
reach
"Inductions of the expression of BRAF V600E, V600K, K601E, L597Q, G469A, G469V, or G464V at levels comparable to those of endogenous BRAF caused significant induction of p-MEK and p-ERK and marked inhibition of RAS-GTP and pCRAF S338."
BRAF-G466V activates ERK. 2 / 2
| 2
reach
"Y472C BRAF and G466V BRAF both activated MEK and ERK to levels at or above those observed after transfection with wt BRAF."
reach
"The BRAF mutants G466V, D594A, D594G, D594E, D594N, D594V and G596C did not induce MEK or ERK activation compared to wt-BRAF."
BRAF-L505H activates phosphorylated ERK. 2 / 2
| 2
reach
"BRAF L505H activates pMEK and pERK and promotes anchorage independent growth of prostate cells."
reach
"BRAF L505H activates pMEK and pERK (XREF_FIG) and promotes anchorage independent growth of prostate cells (XREF_FIG)."
BRAF-V599E activates ERK. 2 / 2
| 2
reach
"However, although most melanoma cells cultured under 2D conditions display active ERK1/2 induced by a ca BRAF V599E mutation, we found that melanoma cell MEK1-ERK1/2 signaling depended on integrin alphav within 3D-collagen."
reach
"This V599E BRAF mutant shows highly elevated kinase activity and stimulates ERK activity constitutively independent of RAS activation."
BRAF-D594V activates ERK. 2 / 2
| 2
reach
"The BRAF mutants G466V, D594A, D594G, D594E, D594N, D594V and G596C did not induce MEK or ERK activation compared to wt-BRAF."
reach
"As we observed, D594V BRAF, even in the presence of CRAF, did not induce strong ERK activity."
BRAF-D594N activates ERK. 1 / 1
| 1
reach
"The BRAF mutants G466V, D594A, D594G, D594E, D594N, D594V and G596C did not induce MEK or ERK activation compared to wt-BRAF."
BRAF-K601E activates ERK. 1 / 1
| 1
reach
"We confirmed this in ' RAS-less ' cells 3 in which MEK and ERK signalling was rescued by BRAF (V600E), BRAF (K601E) or NRAS (Q61K) but not by wild-type, G466V/E or D594N/G BRAF (XREF_FIG)."
BRAF-G469A activates ERK. 1 / 1
| 1
reach
"Although the BRAF G469A is frequently observed in non small cell lung cancer (NSCLC) and known to activate downstream MAPK signaling the responsiveness to BRAF and MEK inhibition is not well studied [XREF_BIBR]."
BRAF-L597Q activates phosphorylated ERK. 1 / 1
| 1
reach
"Inductions of the expression of BRAF V600E, V600K, K601E, L597Q, G469A, G469V, or G464V at levels comparable to those of endogenous BRAF caused significant induction of p-MEK and p-ERK and marked inhibition of RAS-GTP and pCRAF S338."
BRAF-K483E activates ERK. 1 / 1
| 1
reach
"We also confirmed that the BRAF K483E mutant is able to activate ERK1/2 signaling in wild-type MEFs as well as BRAF null MEFs (Additional file 1 : Figure S2E)."
BRAF-G469V activates phosphorylated ERK. 1 / 1
| 1
reach
"Inductions of the expression of BRAF V600E, V600K, K601E, L597Q, G469A, G469V, or G464V at levels comparable to those of endogenous BRAF caused significant induction of p-MEK and p-ERK and marked inhibition of RAS-GTP and pCRAF S338."
BRAF-D594A activates ERK. 1 / 1
| 1
reach
"The BRAF mutants G466V, D594A, D594G, D594E, D594N, D594V and G596C did not induce MEK or ERK activation compared to wt-BRAF."
BRAF-K601E activates phosphorylated ERK. 1 / 1
| 1
reach
"Inductions of the expression of BRAF V600E, V600K, K601E, L597Q, G469A, G469V, or G464V at levels comparable to those of endogenous BRAF caused significant induction of p-MEK and p-ERK and marked inhibition of RAS-GTP and pCRAF S338."
BRAF-D594G activates ERK. 1 / 1
| 1
reach
"The BRAF mutants G466V, D594A, D594G, D594E, D594N, D594V and G596C did not induce MEK or ERK activation compared to wt-BRAF."
BRAF bound to RAP1 activates ERK. 1 / 1
| 1
reach
"Increased intracellular concentrations of cAMP enhanced the Rapgef2 dependent activation of Rap1, which in turn associated with B-Raf to enable the activation of ERK and subsequent neuronal- and endocrine specific cellular outcomes, such as induction of neuroendocrine specific genes and extension of neuritic processes (neuritogenesis)."
Kinase-active BRAF activates ERK. 1 / 1
1 |
bel
"Modified assertion"
BRAF-G464V activates phosphorylated ERK. 1 / 1
| 1
reach
"Inductions of the expression of BRAF V600E, V600K, K601E, L597Q, G469A, G469V, or G464V at levels comparable to those of endogenous BRAF caused significant induction of p-MEK and p-ERK and marked inhibition of RAS-GTP and pCRAF S338."
BRAF-V600K activates phosphorylated ERK. 1 / 1
| 1
reach
"Inductions of the expression of BRAF V600E, V600K, K601E, L597Q, G469A, G469V, or G464V at levels comparable to those of endogenous BRAF caused significant induction of p-MEK and p-ERK and marked inhibition of RAS-GTP and pCRAF S338."
BRAF-D594E activates ERK. 1 / 1
| 1
reach
"The BRAF mutants G466V, D594A, D594G, D594E, D594N, D594V and G596C did not induce MEK or ERK activation compared to wt-BRAF."
BRAF-G596C activates ERK. 1 / 1
| 1
reach
"The BRAF mutants G466V, D594A, D594G, D594E, D594N, D594V and G596C did not induce MEK or ERK activation compared to wt-BRAF."
BRAF-R509H activates ERK. 1 / 1
| 1
reach
"Moreover, BRAF (V600E and R509H) fully activated ERK signaling when expressed in either BRAF-null or ARAF and CRAF-null MEFs (XREF_SUPPLEMENTARY)."
BRAF-G469A activates phosphorylated ERK. 1 / 1
| 1
reach
"Inductions of the expression of BRAF V600E, V600K, K601E, L597Q, G469A, G469V, or G464V at levels comparable to those of endogenous BRAF caused significant induction of p-MEK and p-ERK and marked inhibition of RAS-GTP and pCRAF S338."