IndraLab

Statements

BRAF activates ERK. 284 / 298
| 4 214 66
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 )."
26031292
reach
"Lysine 27 linked ubiquitination of BRAF recruits PP2A to antagonize the S365 phosphorylation and disrupts the inhibitory interaction with 14-3-3, leading to sustained BRAF activation and subsequent elevation of the MEK and ERK signaling."
31015455
sparser
"BRAF activates ERK which in turn activates downstream transcription factors leading to cell differentiation, growth, proliferation and apoptosis xref ."
27144064
reach
"BRAF V600E mutation results in continuous activation of B-raf and downstream activation of MEK and ERK resulting in the activation of several transcription factors and accumulation of cell cycle proteins."
27783987
sparser
"Absence of RAS expression abrogated ERK activation by BRAF F247L and R558Q but had no effect on ERK activation by BRAF L485F and L525R. Based on these data, BRAF A33T was considered to have no effect on ERK signaling, BRAF F247L and R558Q were classified as class 3 mutants, and BRAF L525R and L485F were classified as class 2 mutants."
31515458
reach
"In these islets, the Rap-B-Raf signalling pathway was activated preferentially compared with Ras and Raf-1, and activated Rap and B-Raf mediated ERK stimulation in kinase assays in vitro."
15995848
reach
"A model proposed by Herzinger and Wolf suggests that constitutively active BRAF activates the ERK and MAPK pathway, leading to increased Snail expression in melanoma."
23066033
sparser
"The inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling by LY294002 increased the Erk activation induced by the mutant B-raf proteins, as well as by wild-type B-raf."
15791648
reach
"The finding that the active conformation of B-RAF is sufficient to stimulate endogenous wild-type RAF and ERK represents a novel paradigm for the action of an oncogene.Details of the expression constr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15035987
reach
"XREF_BIBR, XREF_BIBR Sustained ERK signalling by overexpression of B-Raf is reported to protect cells from apoptosis downstream of MOMP, 57 with implications for the resistance of cancer cells to induction of apoptosis."
24787014
reach
"Thus, the formation of BRAF V600E/K homodimers is RAS dependent, but both BRAF V600E/K dimers and monomers can activate ERK signaling."
26343582
reach
"Conversely, inactivating non V600E mutations result in a kinase-dead protein or a protein with lower activity compared to wild-type BRAF, that marginally activates ERK and does not inhibit RAS [17,20][MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29729495
reach
"Previously, we demonstrated that B-RAF and downstream mitogen activated protein and extracellular signal regulated kinase kinase (MEK) signaling are necessary for protection from anoikis in mutant B-RAF-expressing melanoma cells."
18246127
reach
"ERK signaling is driven by oncogenic RAS and RTK proteins, as well as by mutational activated BRAF proteins."
29312543
reach
"Oncogenic mutations in RAS or BRAF can drive the inappropriate activation of the ERK1/2."
23647573
sparser
"Importantly, in a set of human cancer cells with Src-, Kras- or BRAF-dependent activation of Erk1/2, resistances to staurosporine or thapsigargin were also shown to depend on Bik degradation rate via a similar mechanism."
22388352
reach
"We hypothesize that mutation in the BRAF pathway causes hyper-activation of ERK and thus, combining EGFR inhibition with BRAF inhibition would be of benefit."
25706985
reach
"We find that the 50% induction of p61 WT BRAF driven ERK signaling by vemurafenib is also approximately 100-300 nM (XREF_SUPPLEMENTARY)."
26343582
reach
"However, the ChIP assay showed that inhibition of the BRAF V600E / ERK signaling by si-BRAF or trametinib could significantly reduce the binding of GABPA to mutant TERT promoter in the indicated cells."
33483600
reach
"Since the myeloid cells that cause this tissue macrophage disorder share a similar yolk sac progenitor as microglia, BRAF mediated ERK hyperactivation in resident brain microglia partly underlie the pathogenesis of this progressive neurodegenerative condition [XREF_BIBR]."
31597593
reach
"The syndrome is caused by gain-of-function mutations in four different genes BRAF, KRAS, mitogen activated protein and extracellular signal regulated kinase MEK1 and MEK2, all belonging to the same RAS-extracellular signal regulated kinase (ERK) pathway that regulates cell differentiation, proliferation and apoptosis."
16825433
sparser
"D593V B-RAF cannot phosphorylate MEK in vitro and does not activate C-RAF, ERK, or NF-κB in cells (Ikenoue et al., 2003; Wan et al., 2004) ."
15488754
reach
"Oncogenic mutations in KRAS or BRAF are frequent in colorectal cancer and activate the ERK kinase."
31266962
reach
"Consistent with the lack of effect of 21 on G , it did not inhibit AT1R-mediated PKC activation (Supplementary Fig. 4b), nor did it block ERK1/2 activation induced by the overexpression of either the active forms of MEK1 (MEK1-DD) or BRAF (BRAF-V600E) (Supplementary Fig. 4c, d)."
34344896
reach
"XREF_BIBR This genetic alteration of BRAF sequentially induces constitutive extracellular signal regulated kinase (ERK) signaling through a hyperactivation of the RAS/RAF/mitogen activated protein kinase and ERK (MAPK and ERK) pathway that is involved in promoting the proliferation, survival and development of tumor cells."
23110010
reach
"For example, the RAF kinase family consists of three members : ARAF, BRAF and CRAF each of which can activate MEK and ERK signaling XREF_BIBR."
21479172
reach
"One was the highly aggressive triple negative (ER -, PR - and HER2 -) MDA-MB231 cell line, which carries oncogenic mutations in KRAS and BRAF genes, shows enhanced PKCtheta activity and accumulates high levels of Fra-1 as a result of stabilizing phosphorylations by both KRAS- and BRAF activated Erk pathway kinases and PKCtheta."
25200076
sparser
"This conclusion is based on results showing that ERK activation induced by kinase-dead BRAF requires CRAF but occurs normally in the absence of BRAF ( xref ; xref ; xref ; xref )."
23993095
reach
"Mutations in KRAS or BRAF can cause constitutive activation of MAP/ERK1/2 kinase (MEK1/2) and ERK1/2 in cancer cells which account for their malignancy."
18676857
reach
"BRAF mediated ERK activation induced Snail1 and down-regulated CYLD in melanoma cells."
19124656
sparser
"While activation of ERK1/2 by BRAF V600E in melanoma cells inhibits Wnt/β-catenin signaling xref , forced expression of BRAF V600E enhances Wnt/β-catenin signaling in normal melanocytes ( xref )."
24733413
reach
"Activation in BRAF gene is known to induce aberrant activation of ERK MAPK pathways in mice, human and canine cells XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR."
32385388
sparser
"cAMP can activate Rap1 through PKA, resulting in the activation of B-raf, which, in turn, can activate MEK and ERK ( Dugan et al., 1999; Kolch, 2000 )."
11985830
reach
"Several recent studies therefore only included patients carrying the BRAF V600E/K mutation, which has been shown to consistently activate ERK and has also been closely examined in a variety of other tumors."
| PMC
sparser
"As in COS cells, D593V B-RAF and KD B-RAF did not activate ERK in Xenopus cells (Figure 2E) ."
15035987
sparser
"In these cells PKA leads to the activation of the serine-threonine-kinase B-Raf, which in turn activates MEK and ERK 11 ."
12753285
sparser
"BRAF activates the MAP kinase extracellular signal regulated kinase (MEK), which in turn phosphorylates and activates extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2)."
18267069
reach
"PDX models indicate that dual inhibition of BRAF and FAK inhibits ERK/MAPK re-activation in the tumor stroma, which facilitates the efficient therapeutic control of BRAF-mutant melanoma [51, 139]."
32546182
sparser
"Thus, despite possessing widely differing in vitro kinase activities, individual B-RAF mutants activated ERK to similar levels as G12V RAS."
15035987
sparser
"This suggests that constitutive ERK activation by BRAF V600E exaggerates a physiological role for ERK activity in negatively regulating DC migration."
29263218
sparser
"Activation of AMPK prevents BRAF inhibitor-induced hyper-activation of ERK and proliferative response in keratinocytes and mouse skin."
24095280
sparser
"In melanoma and papillary thyroid carcinoma, ERK activated by mutated BRAF induces direct phosphorylation of ETS1 [ xref ] or phosphorylation of another transcription factor FOS followed by GABPB transcriptional activation [ xref ]."
30709063
sparser
"However, this mechanism is dispensable for MEK-ERK activation by oncogenic BRAF V600E mutant, which “bypasses” RAF1 and directly phosphorylates MEK1 ( xref )."
35417664
reach
"Based on our findings, BRAF inhibition blocks CDC7-downstream MCM2 and ERK1/2 activities in parental, but not in resistant cells."
31578454
reach
"Similarly, oncogenic mutations in BRAF do not fully activate downstream ERK when intracellular mechanisms controlling senescence and/or apoptosis are active."
26322273
reach
"In fact, in wild-type cells, BRAF and CRAF form homo- and heterodimers on RAS activation; vemurafenib binding to one member of the dimer causes an allosteric transactivation of the drug-free protomer and activation of MEK and ERK."
25344914
reach
"Novel fusion gene products with BRAF that demonstrate constitutive kinase activity and increased downstream ERK signaling sensitive to MEK inhibition preclinically have also been described XREF_BIBR, XREF_BIBR."
27144064
sparser
"The mutated B-Raf can activate MEK and ERK downstream, and activate Raf-1 in wild-type and mutant-type B-Raf, thus further activating MEK and ERK ( xref )."
27899961
reach
"BRAF inhibition causes a decrease in ERK activation resulting in G1 phase cell cycle arrest and inducing endoplasmic reticulum (ER)-stress-mediated cell death XREF_BIBR - XREF_BIBR."
29487283
sparser
"As shown in xref , ERK activated by BRAF co-localizes with METTL3 and WTAP in the nucleus, suggesting that METTL3 complex could be a nuclear substrate of ERK."
33217317
reach
"The activation of ERK by B-Raf was completely inhibited by the PKA inhibitor, H89, thus cAMP stimulates B-Raf through the intermediate effect of activated PKA."
12753285
reach
"Dabrafenib, an inhibitor of RAF-1 and B-RAF, suppressed the early activation of ERK, but a significant amount of phosphorylated ERK remained after 60min of shaking in the presence of dabrafenib (XREF_FIG A), which gradually increased over time only when FSS was applied (XREF_FIG C)."
28956013
reach
"Studies revealed mutually exclusive NRAS and BRAF activating mutations driving the MAPK and ERK pathway among human melanomas."
27572939
reach
"Subsequently, the activated BRAF serine threonine kinase upregulates downstream signaling to mitogen activated protein kinase kinase (MEK) and extracellular signal regulated kinase (ERK), respectively, leading to an oncogenic gain-of-function in the affected cell."
24348046
reach
"The autosomal dominant, human syndromes Noonan, Costello, cardiofaciocutaneous, and LEOPARD result from mutations in PTPN11, HRAS, RAF1, BRAF, MEK1, and MEK2 that activate ERK1/2 signaling."
22997248
reach
"RAF1 (D486N), as well as other kinase impaired RAF1 mutants, showed increased heterodimerization with BRAF, which was necessary and sufficient to promote increased MEK and ERK activation."
22826437
sparser
"Mutant BRAF constitutively activates the downstream kinases, MEK and ERK, within the mitogen-activated protein kinase (MAPK) pathway, leading to uncontrolled cell proliferation."
26918352
reach
"This pathway appears to be uniquely activated by alpha-adrenergic stimuli since Raf-1 and B-Raf was necessary for activation of ERKs downstream of growth factor receptors and oxidative stress."
21998323
reach
"Approximately 40% to 50% of malignant melanomas express mutation in BRAF, a protein kinase that activates the MAP kinase and ERK signaling pathway, causing cell growth and cancer replication [XREF_BIBR]."
29796327
reach
"It has been reported that BRAF mediated ERK and RSK activation negatively regulates LKB through phosphorylation at Ser428, and subsequently inhibits activation and phosphorylation of AMPK [XREF_BIBR]."
26771234
sparser
"For example, a previous study demonstrated that RKIP regulates Raf-1, but not B-Raf, indicating that B-Raf is able to phosphorylate and activate MEK and ERK independent of RKIP ( xref )."
25663894
sparser
"Given that BRAF inhibitors activate ERK, one might expect MEK inhibitors to do the same; however, this is not the case."
21495172
reach
"XREF_FIG shows that FAK kinase inhibition does not affect phospho-ERK1/2 levels, consistent with mutant-BRAF driving ERK activity in these cells."
27259715
reach
"Our results suggest that : (i) extracellular signal regulated kinase is activated by B-Raf in response to a calcium sensitive adenylate cyclase; and (ii) extracellular signal regulated kinase activates casein kinase-2 via a protein phosphatase (s) that may be of the PP1 and/or PP2A type."
10670437
reach
"The BRAF V600E mutation directly leads to activation of MEK although other mutations in BRAF appear to indirectly activate ERK through CRAF and not MEK."
19707310
reach
"One of these, BRAF is constitutively activated by point mutations in a range of human cancers, resulting in uncontrolled ERK activation and cell proliferation [1]."
17324460
reach
"All mutations in BRAF confer increased kinase activity compared with the wild-type protein, and thereby stimulate MAPK/ERK activity in a Ras-independent manner."
31353365
reach
"Thus, it appears that BRAF driven ERK and S6K activation alone is not sufficient to drive androgen independent growth post castration, although it appears to be permissive of survival in low androgen state."
19079609
reach
"A BRAF p.V600E/K variant results in constitutively activated kinase activity and increased downstream MEK and ERK activation."
33637608
reach
"MDA-MB-231 cells typically exhibited greater activation of Akt than ERK because mutant KRas and BRaf in these cells constitutively drive ERK signaling, reducing the dynamic range for activation by CXCR4."
31289212
sparser
"WT B-RAF did not activate ERK in Xenopus cells, whereas V599E B-RAF and the three impaired activity mutants that activate ERK in COS cells induced strong activation in Xenopus cells (Figure 2E) [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15035987
reach
"Landmark studies have revealed largely mutually exclusive N-RAS, BRAF, and c-KIT activating mutations driving the MAPK and ERK pathway among human melanomas and defining therapeutically relevant melanoma subsets."
22588879
reach
"Association of Rap1 GTP with RafB, a close relative of Raf1 [80] and with protein kinase C [81] leads to activation of these kinases in vitro.Recent evidence in fibroblasts and the neuronally derived [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
9395281
reach
"The constitutive BRAF kinase activation and the following MEK and ERK kinases activation plus the activated MAPK pathway are supported by BRAF V600 mutations."
32470910
reach
"This suggested that the ability of kinase-dead forms of BRAF to activate ERK requires residues between 434 and 454."
23993095
reach
"BRAF V600 R509H mutants restore ERK signaling in these cells, but R509H mutants of non V600 BRAF mutants do not."
26343582
reach
"Taken together, these results suggest that Raf-1 inhibits ASK1 in an MKK and ERK independent manner, and also suggest that B-Raf and A-Raf function in parallel with Raf-1 to promote ERK1/2 activation in heart."
18752467
reach
"Given that BRAF and PTPN11 promote MAPK/ERK signaling, we investigated whether activation of this pathway is associated with response to PD-1 inhibitors in rGBM, including patients that do not harbor BRAF/PTPN11 mutations."
35121903
sparser
"A recent study demonstrated that RKIP regulated Raf-1, but not B-Raf [29] , suggesting that B-Raf can activate ERK independent of RKIP."
20688353
reach
"Oncogenic mutations of NRAS, KRAS, BRAF, MEK1, and NF1 drive the ERK dependent growth of many human cancers."
26343582
reach
"Substitution of BRAF lysine 578 with arginine (K578R) inhibited BRAF mediated ERK activation."
23907581
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."
25417704
sparser
"Persistent and sustained ERK1/2 activation, induced by mutant BRAF or KRAS, leads to mitochondrial translocation of phosphoglycerate kinase 1 (PGK1) and phosphorylation of PDK1, which in turn inactivates PDH, contributing to aerobic glycolytic switch in cancer ( xref )."
32528879
reach
"Activation of B-Raf by Rap1 promotes ERK activity, linking AC/cAMP signaling to ERK mediated neuronal survival."
18992344
reach
"34 As we revealed that activity of PRMTs is reduced in tumour cells by accumulation of MTA, potentially also other PRMTs have functions independent of their catalytic activity and, thus, are still mod[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23265702
sparser
"For instance, increased cell invasion can be mediated by the BRAF mutation-induced activation of phosphorylated extracellular-signal-regulated kinase (pERK), phosphorylated mitogen-activated protein kinase (pMEK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and metalloproteinases activity [ xref ]."
| PMC
reach
"Remarkably, expression of an activated form of Braf in Shp-2-deficient mice restores ERK activation, goblet cell production, and prevents colitis."
30376595
reach
"Strong ERK1/2 activation by oncogenic KRAS and BRAF does not repress activation of ERK5 in HEK293 cells."
26959608
sparser
"We determined that a full-scale activation of ERK1/2 by BRAF V600E in melanocytes requires KLF9-dependent ROS."
30664687
reach
"Conversely, ERK-nKTR is excluded from the nuclei of all VPCs when MPK-1 and ERK is activated by uniform expression of a highly active and stable form of LIN-45 and Braf in all VPCs (transgene arTi31, see STAR Methods), (XREF_FIG), similar to the phospho-mimetic ERK-nKTR (EEE) (XREF_FIG)."
28826819
reach
"B-Raf V600 0E induces activation of MEK and ERK in cell culture experiments and in vitro kinase assays (Houben et al., 2004)."
18650848
reach
"Silencing the expression of B-Raf also inhibited ERK activation by TSH, forskolin, and 6MB-cAMP, but not that stimulated by insulin or serum."
19720729
reach
"In MDA-MB-231 cells, the Ras and Erk pathway is activated by mutations in both K-Ras and B-Raf (http://www.sanger.ac.uk/perl/genetics/CGP/cosmic?action=sample&id=905960)."
19903845
reach
"280Moreover, our data provide molecular basis to this activity through the identification of BRAF 281 as a new interactor of BTV-NS3 together with the fact that BRAF silencing impairs BTV-282 activated MAPK/ERK signaling."
| DOI
reach
"Using a panel of melanoma cell lines derived from the establishment of excised primary and metastatic tumours, we have investigated the ability of dabrafenib to both exert an antiproliferative activity on cultured melanoma cells and block the ERK signalling induced by the mutated BRAF."
23317446
reach
"This may result from mutational activation of components of the downstream signaling pathways, such as PIK3CA or BRAF, that directly activate the PI3K and AKT and MEK and ERK pathways, respectively, or activation of another RTK that sustains downstream signaling despite inhibition of the oncogenic RTK."
24065147
reach
"Using a conditional knock-in mouse model, we show that endogenous expression of (L597V) Braf leads to approximately twofold elevated Braf kinase activity and weak activation of the Mek and Erk pathway."
22892241
sparser
"Here we show that the 3 proteins function along a linear oncogenic signaling cascade in which RET/PTC induces RAS-dependent BRAF activation and RAS- and BRAF-dependent ERK activation."
15761501
sparser
"TMRM and calcein-AM staining showed that opening of the mitochondrial permeability transition pore (mPTP) during STS-induced cell death could be significantly inhibited by BRAF V600E. Moreover, our study demonstrated that BRAF V600E constitutively activates mitochondrial ERK (mERK) to inhibit GSK-3-dependent CypD phosphorylation, thereby making BRAF V600E mutant tumour cells more resistant to mPTP opening."
35748101
reach
"However, therapies targeting mutated BRaf or MEK1/2 proteins invariably lead to drug resistance due to alternative mechanisms to activate ERK1/2 and recent efforts to directly inhibit ERK1/2 proteins are being tested [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
25695333
reach
"With respect to BRAF inhibitors, the observation that BRAF selective agents activate ERK signaling in non-BRAF-mutated tumors raises the concern that not only would these agents not be effective in CS or CFC, but they may be contraindicated in non oncology settings by promoting the growth of keratoacanthoma skin lesions."
21495172
reach
"Colorectal cancers (CRC) often show activating mutations of the KRAS or BRAF genes, which stimulate the extracellular signal regulated kinase (ERK) pathway, thus increasing cell proliferation and inhibiting apoptosis."
27036313
reach
"Co-inhibition of BRAF and FAK abolished ERK reactivation and led to more effective control of BRAF-mutant melanoma."
25873177
reach
"Supporting its classification as an oncogene, (V600E) BRAF stimulates ERK signaling, induces proliferation, and is capable of promoting transformation."
21818706
sparser
"Using reporters, single cell transcriptomics and mass cytometry, we observe cell type-specific phosphorylation of ERK in response to transgenic KRAS G12V in mouse intestinal organoids, while transgenic BRAF V600E activates ERK in all cells."
31266962
eidos
"In BC , BRAF , the most important member of RAF , can activate ERK through phosphorylation to promote proliferation and invasion.19 Therefore , we evaluated the protein levels involved RAF / ERK pathway ."
32523377
reach
"It has been shown that in MSI CRC cell lines, BRAF is the main activator of ERKs and these cells are more dependant on the BRAF-ERK pathway (Preto et al, 2008)."
20485284
reach
"In case of BRAF V600E, autoinhibiton of BRAF is prevented which results in hyperactivation of ERK."
29983861
sparser
"This input of ERK activation from ERBB3 may be more essential and abundant for cell lines expressing BRAF WT than for those expressing BRAF V600E , which activates ERK constitutively."
25000258
reach
"BRAF, which can be constitutively activated by several mutations in melanomas, stimulates constitutive ERK signaling in tumor cells."
19738072
reach
"Inhibitors of BRAF (BRAFi e.g. dabrafenib) and MEK (e.g. trametinib) prevent ERK activation and are the standard-of-care for treatment of BRAF mutant melanoma."
31362929
reach
"Karasarides et al. (2004) showed that B-RAF depletion by siRNA blocked ERK activity, inhibited DNA synthesis, and induced apoptosis in three melanoma cell lines."
15908010
reach
"In melanoma cell lines, which have acquired resistance to the RAF inhibitor, elevated CRAF protein levels accounted for the acquisition of resistance to RAF inhibitor, and CRAF, but not BRAF activated the MEK and ERK pathway XREF_BIBR."
25422890
reach
"AMPK also abrogates ERK signaling in many cell types, and this effect has recently been linked to negative regulation of the upstream ERK activator BRaf (Fig. 2b) (Shen et al. 2013)."
25846612
reach
"18 Ras and Rap normally signal via B-Raf to activate ERK XREF_BIBR, XREF_BIBR because under normal conditions, cAMP activation of PKA phosphorylates key inhibitory sites on C-Raf, preventing it from activation."
22105816
sparser
"In BC, BRAF, the most important member of RAF, can activate ERK through phosphorylation to promote proliferation and invasion. xref Therefore, we evaluated the protein levels involved RAF/ERK pathway."
32523377
reach
"Aside from stimulating MAPK/ERK signaling, BRAF p.V600E induces cell proliferation and is capable of promoting transformation, which collectively supports its classification as an oncogene [24]."
35048058
reach
"Thus, negative feedback limits the amplitude and duration of the ERK signal.Oncogenic mutations of NRAS, KRAS, BRAF, MEK1, and NF1 drive the ERK dependent growth of many human cancers."
26343582
reach
"According to the analysis, increasing BRAF activity might not mainly cause ERK pathway activation in NSCLC.In our analysis, BRAF mutation only was found from adenocarcinoma but not from squamous cell [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16376942
reach
"Seven of the BRAF V600E-mutant gliomas were treated with diverse MAPK directed therapy (RAF, MEK, ERK, or RET inhibitor therapy)."
31263031
sparser
"The activation of ERK by B-Raf was completely inhibited by the PKA inhibitor, H89, thus cAMP stimulates B-Raf through the intermediate effect of activated PKA."
12753285
reach
"The Raf kinases Raf-1 and B-Raf are upstream activators of the extracellular signal regulated kinase (ERK)-signaling pathway and therefore participates in many physiological functions in brain, including neuronal survival and synaptic plasticity."
16172610
sparser
"Conversely, inactivating non-V600E mutations result in a kinase-dead protein or a protein with lower activity compared to wild-type BRAF, that marginally activates ERK and does not inhibit RAS [17,20[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29729495
reach
"BRAF V600 mutations induce RAS independent activation of the ERK pathway, with consequent dysregulation of ERK signaling (high expression and activation of ERK), driving cell proliferation and survival 39."
30630828
reach
"Using this vector in a murine syngeneic BM transplantation model for BCR-ABL-induced chronic myeloid leukemia, we find that oncogene expression and target knockdown in primary hematopoietic cells with this vector is efficient both in vitro and in vivo, and demonstrate that Raf1, but not BRAF, modulates BCR-ABL-dependent ERK activation and transformation of hematopoietic cells."
21715303
sparser
"In preclinical models, the association of a MEK inhibitor (PD184352) with an analog of vemurafenib (PLX4720) blocked the paradoxical ERK activation induced by the BRAF inhibitor and prevented the appe[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24210882
reach
"ERK activation through both TPalpha and TPbeta was dependent on PKA and phosphoinositide 3-kinase (PI3K) class 1 (A), but not class 1 (B), and was modulated by Harvey-Ras, A-Raf, c-Raf, and Rap1B and B-Raf and also involved transactivation of the epidermal growth factor receptor."
11901221
reach
"Effect of increasing Dabrafenib or AZ628 concentrations independently or in combination with Trametinib on BRAF induced ERK pathway activity."
29662630
reach
"cAMP can activate Rap1 through PKA, resulting in the activation of B-raf, which, in turn, can activate MEK and ERK (Dugan et al., 1999; Kolch, 2000)."
11985830
reach
"Interestingly, B-Raf and C-Raf double knockdown, not A-Raf and B-Raf knockdown, inhibited the maximal ERK activation induced by LIF, concomitant with the slower growth of ES cells."
24051329
reach
"In a non cancer setting, BRAF activates kinases MEK and ERK, which in turn activate transcriptional machinery to promote differentiation, proliferation, growth and apoptosis [XREF_BIBR]."
29616301
reach
"BRAF and MEK inhibitors both inhibit the MAPK pathway and the ERK production."
28640105
sparser
"Here, the authors use single cell analysis in intestinal organoids and show that BRAF V600E activates ERK in all intestinal cell types, while KRAS G12V induces ERK activation in only a subset of cells, depending on cell differentiation state."
31266962
sparser
"These data suggest that in some class 2 BRAF mutants, while mutant BRAF activates ERK, an additional contribution to ERK activation can come from upstream signaling."
31515458
reach
"Mutations in the serine/threonine kinase BRAF (mutant v-raf murine sarcoma viral oncogene homolog B1) that activate ERK1/2 signaling are found in 7% of human cancers with a high frequency (45-50%) in cutaneous melanoma."
24121492
reach
"More than 50% of melanomas, a common and deadly form of skin cancer, contain a constitutively active mutant of the kinase BRAF (BRAF ) that causes inappropriate ERK signaling, a dominant driver of human melanoma ."
31745079
reach
"Ectopic B-Raf expression enhances extracellular signal regulated kinase (ERK) signaling in T cells and prevents antigen presenting cell induced anergy."
12855697
reach
"Together, these in vitro and in vivo mechanistic data predict that BRAF kinase inhibitors will not inhibit ERK signaling in normal cells and therefore the toxicity associated to MAPK inhibition would be low."
21981139
reach
"It was previously reported that MLK3 acts as a scaffold for BRAF to activate the MEK and ERK pathway, however our data demonstrate that the MLKs act directly at the level of MEK, and through phosphorylation of MEK can activate ERK."
24849047
reach
"By dimerizing with wild-type CRAF, kinase-dead forms of BRAF can activate MEK and subsequently ERK."
23993095
reach
"However, combined inhibition of EGFR and BRAF blocks re-activation of ERK and leads to regressions of BRAF mutant CRC in vivo."
24651011
reach
"In normal cells, B-Raf is repressed by Akt (protein kinase B), a Ca (2+)-dependent kinase, preventing cAMP activation of ERK and cell proliferation."
21118718
reach
"The B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor GDC-0879 induced paradoxical ERK1/2 activation as previously described [22], and partially rescued the effect of RAC1 knockdown."
29329780
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)."
28783719
reach
"Thus, ERK signalling driven by BRAF (G466V/E) and BRAF (D594N/G) is limited by ERK dependent feedback inhibition of RAS, and signalling of RAS independent BRAF mutants is not."
28783719
reach
"BRAF activates the MAP kinase/ERK signaling pathway for normal cell control and proliferation."
36329938
reach
"[XREF_BIBR] The syndrome is caused by gain-of-function mutations in four different genes BRAF, KRAS, mitogen activated protein and extracellular signal regulated kinase MEK1 and MEK2, all belonging to the same RAS extracellular signal regulated kinase (ERK) pathway that regulates cell differentiation, proliferation and apoptosis."
22837569
reach
"However, unlike (V600E) Braf, Mek and Erk pathway activation was mediated by both Craf and Braf, and ATP-competitive RAF inhibitors induced paradoxical Mek and Erk pathway activation."
22892241
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."
27222248
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."
24201813
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."
22351689
reach
"Davies et al. (2002) first discovered that mutated BRAF constitutively activates downstream ERK activity, which drives carcinogenesis through increased cell-cycle entry and suppression of apoptosis."
26708040
sparser
"In the BRAF mutant cells, AKT and ERK are regulated by similar positive and negative pathways as that in the KRAS mutant cells, except that ERK is activated by the mutant BRAF instead of KRAS."
28002807
sparser
"Although reports have shown that plexin B1 activates ERK in other cell systems ( xref ), this appears not true in melanoma, where ERK is already constitutively activated by oncogenic B-Raf."
19483722
reach
"TRAF1 KD led to decreased BRAF protein expression, decreased downstream MEK/ERK activation, and inhibited cell growth in human lung cancer cell lines [48]."
34759347
reach
"Studies have reported that BRAF/KRAS induces the activation of the MAPK/ERK signaling pathway, triggering colon cancer 13."
35003370
eidos
"Overexpression of B-Raf not only activated ERK signaling but also regulated cyclin E and CDK2 ( Fig. 6g ) ."
30634993
reach
"Moreover, MBZ also potently inhibits BRAF which in cells with wild type RAF leads to paradoxical ERK activation ."
32753665
sparser
"Likewise, we observed that K483M B-Raf hardly activated its downstream effectors MEK1/2 and ERK1/2 (Figure 3D, lane 3)."
20824047
reach
"Deregulation of this pathway by RAS and more recently BRAF oncoproteins induce constitutive ERK1/2 activation, thereby promoting cell growth and survival."
21738740
reach
"BRAF, KRAS and NRAS are key oncogenes in the ERK signalling pathway, and activating mutations in BRAF, KRAS, and NRAS functionally overlap, inducing continuous stimulation of the ERK pathway [XREF_BIBR - XREF_BIBR]."
26220863
reach
"Collectively, these data indicate that high Snail1 expression modulated by BRAF mediated ERK activity is involved in the transcriptional down-regulation of CYLD in melanoma."
19124656
reach
"Mutations in BRAF, NRAS, and NF1 lead to constitutive activation of the rat sarcoma viral oncogene homolog (RAS)/v-raf-1 murine leukemia viral oncogene homolog (RAF)/mitogen-activated protein kinase a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28143781
reach
"Signal activation through RAS enzymes is low when BRAF is mutated, so ERK signalling is predominantly activated by mutated BRAF."
23207060
reach
"In a majority of human cancers, the PI3K and AKT pathway is frequently activated by the activating mutations of PI3K p110alpha (PIK3CA) and the loss or inactivating mutation of PTEN, whereas hyper activation of MEK and ERK signaling driven by mutant RAS and BRAF is also a common oncogenic event in a variety of cancers [XREF_BIBR, XREF_BIBR]."
26005705
reach
"Similar to a previous study 20, inhibition of BRAF V600E / ERK signaling by si-BRAF or trametinib almost did not change the expression of total Sp1 (t-Sp1), while markedly decreased the levels of phosphorylated Sp1 (p-Sp1)."
33483600
reach
"Hence, Erk activation by B-Raf (V600E)/MEK, combined with suppression of its de-phosphorylation by MEDICA induced ROS, may account for Erk hyper-activation, resulting in growth arrest and apoptosis of B-Raf (V600E) cancer cells."
26959890
reach
"The reason for this difference may be that the expression of the BRAF gene activates the extracellular signal regulated kinase Erk1/2, leading to cell diffusion [XREF_BIBR]."
33123592
reach
"How these mutant forms of B-Raf then go on to activate ERK is not known, but one possibility is that the active conformation of B-Raf can stimulate the activation of c-Raf, by an as yet unidentified mechanism."
15239827
reach
"Increased MAP and ERK kinase (MEK) activity is a feature of many cancers, and is often triggered by missense mutations in BRAF and NRAS, two upstream oncogenes and potent regulators of Ras/Raf/Mek/ERK signaling."
30838036
sparser
"The most common mutation in melanoma is located on the BRAF gene [ xref , xref ] which activates sequentially mitogen-activated protein kinase (MEK 1/2) and extracellular signal-regulated kinase (ERK1/2) leading to cell proliferation [ xref ]."
34065911
sparser
"BRAF activates the MAP kinase extracellular signal regulated kinase (MEK), which in turn phosphorylates and activates extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2)."
24112705
reach
"Because Braf induced Mapk signaling does not seem to engage intrinsic tumor suppression in early tumorigenesis, we next assessed the MAPK pathway activity at different stages of tumor evolution."
23845441
reach
"We demonstrated that BRAF p.K483E expression increased ERK1/2 activation despite the BRAF p.K483E mutant harboring a catalytically dead kinase domain."
27799065
reach
"BRAF underlies ERK activation in most TC cells, but not in TPC-1 cells with RET and PTC1 rearrangement."
26265449
reach
"Cytoplasmic SPOP binds to and induces non-degradative ubiquitination of BRAF, thereby reducing the interaction between BRAF and other core components of the MAPK/ERK pathway."
36585710
sparser
"BRAF Inhibitors Activate MEK and ERK in RAS Mutant Melanoma Cells."
20141835
reach
"In melanoma cells harboring the NRAS mutation, the mutated NRAS protein needs CRAF to activate the MEK and ERK pathway XREF_BIBR, and the BRAF protein is phosphorylated by ERK on S151 near the RAS binding domain, which results in the inhibition of the NRAS and BRAF interaction XREF_BIBR."
25422890
reach
"Both KSR1 and B-Raf are feedback phosphorylation targets of ERK and these feedbacks are enhanced by docking of ERK."
23267331
reach
"BRAF inhibition by RNAi strongly reduces ERK activation in the cell line harbouring the BRAF V600E mutation, is also effective in the cell line with RAS G13R, but has no effect in ERK activation in the cell line with RET and PTC rearrangement."
19878585
reach
"As previously discussed, these active mutations in BRAF constitutively upregulate downstream MAPK and ERK signaling, thereby promoting cell proliferation and metastasis [XREF_BIBR]."
26393652
reach
"This conclusion is based on results showing that ERK activation induced by kinase-dead BRAF requires CRAF but occurs normally in the absence of BRAF."
23993095
reach
"As we anticipated, expression of the active Ras or BRaf increased ERK activity at low cell densities."
27936234
reach
"Importantly, in a set of human cancer cells with Src-, Kras- or BRAF dependent activation of Erk1/2, resistances to staurosporine or thapsigargin were also shown to depend on Bik degradation rate via a similar mechanism."
22388352
reach
"This argues for a regulatory role of Spry and Spred proteins in melanoma aggressiveness independent of oncogenic BRAF driven ERK hyperactivation."
22535842
reach
"Together these results demonstrate that oncogenic forms of BRAF and KRAS can activate ERK1/2 but can not activate ERK5 in HEK293 cells."
26959608
reach
"Additionally, BRAF, PA28γ, and MEK1 could form protein complexes and then enhance the MEK1/ERK signaling pathways."
35961969
sparser
"Collectively, these data suggest that full-scale activation of ERK1/2 by BRAF V600E requires KLF9 or KLF9-dependent ROS in NHMs."
30664687
reach
"Protein kinase A and B-Raf mediate extracellular signal regulated kinase activation by thyrotropin."
19720729
reach
"The missense BRAF mutation that results in a valine (V) to glutamic acid (E) substitution at codon 600 (BRAF p.V600E) constitutively activates MAPK/ERK pathway [21] (Figure 1B)."
35048058
reach
"c-Raf is thought to be responsible for the transient activation of the ERK pathway required for proliferation upon epidermal growth factor stimulation, while B-Raf causes a persistent activation of ERK required for differentiation in response to stimulation with nerve growth factor [XREF_BIBR], consistent with our observations."
19232538
reach
"ERK is also activated in a variety of cancers by BRAF deregulation [XREF_BIBR]."
23434669
reach
"This pathway is driven by hypermethylation of genes and is characterized by the presence of protooncogene BRAF (protein kinase B-Raf), which causes increased MAPKs and ERKs (mitogen activated protein kinases and extracellular signal regulated kinases) signaling, leading to increased cell proliferation, cell division, and secretion [XREF_BIBR]."
25685149
sparser
"Ephrin-A1 stimulation also caused Akt but not Erk1/2 inactivation in several melanoma cell lines expressing the B-Raf V600E mutant, which constitutively activates Erk1/2 ( xref )."
20837138
reach
"The A728V mutation in the BRAF gene strongly activates ERK1/2 XREF_BIBR and is only observed in Jurkat cells."
29187889
eidos
"MDA-MB-231 cells typically exhibited greater activation of Akt than ERK because mutant KRas and BRaf ( 16 ) in these cells constitutively drive ERK signaling , reducing the dynamic range for activation by CXCR4 ."
31289212
reach
"This acquired resistance to vemurafenib is frequently associated with re-activation of the ERK1/2 pathway that is mediated by secondary mutations in NRAS or MEK1 and the expression of BRAF slice variants."
23490205
sparser
"It was found that cell death induced by either PTPRκ or KDELr-HV12 could be prevented by the co-expression of MEK1E, known to yield a constitutive ERK activation, or by BRAF that activates ERK mostly independently of CRAF (Fig.  xref )."
30185827
reach
"In fact, 85-90% of papillary carcinomas possess RET, NTRK1, BRAF or RAS mutations that induce MEK and ERK signaling."
18701481
sparser
"Furthermore, it raises the question to what extent mutant KRAS and BRAF activate downstream ERK in a fully autonomous fashion."
33795873
reach
"Indeed, the oncogenic activation of BRAF drives the inappropriate activation of ERK signaling and the deregulation of cell proliferation [XREF_BIBR], and is responsible for the inhibition of the mitochondrial apoptotic pathway [XREF_BIBR - XREF_BIBR], the latter being consistent with the apoptosis resistant phenotype of BRAF driven cancer cells."
26084290
reach
"For instance, in vitro studies have suggested that BRAF inhibition suppresses ERK-mediated negative feedback on EGFR activity, resulting in EGFR activation, the formation of RAF protein dimers and CRAF-mediated reactivation of the ERK/MAPK signalling pathway."
31353365
reach
"Treatment of 2 melanoma cell lines, UCT-2 and A2058, both of which express alpha5beta1-integrin and have highly activated ERK induced by mutated B-RAF, but no uPAR expression (Estrada, Y. Dong, J-L."
19242538
sparser
"Interestingly, Vemurafenib treatment increased both the intrinsic kinase activity of endogenous ARAF ( xref ) and ERK activation ( xref ) in double BRAF- and CRAF-deficient resistant cultures, demonstrating that ARAF homodimers are sufficient to sustain ERK paradoxical activation by BRAF inhibitor in the absence of other RAF proteins."
28497782
reach
"The experiment was performed in triplicates, and data represent BRAF silencing impairs activation of MAPK/ERK pathway by BTV."
| DOI
reach
"Available data suggest that the most frequent mutational events in these carcinomas are mutations in B-RAF, leading to activation of the RAF and MEK (mitogen activated protein and extracellular signal regulated kinase (ERK) kinase)/ERK pathway and in phosphoinositide 3-kinase (PI3K)/AKT signalling."
19808899
reach
"Western blotting of zebrafish embryonic lysates for total ERK protein and phospho-ERK confirmed that all BRAF and MEK alleles caused ERK activation in the zebrafish embryo."
19376813
reach
"In previous studies, the high expression of BRAF increased the activity of ERK in the Rat-1 cell line, and also stimulated the growth of malignant melanoma cells."
29286077
reach
"In this study, we identified a signaling pathway that promotes mitogenic and metastatic properties of melanoma by down-regulation of CYLD through the action of Snail1, whose expression is induced by BRAF mediated activation of extracellular signal regulated kinase (ERK)."
19124656
reach
"BRAF V600 R509H mutants restore ERK signaling in these cells, R509H mutants of non V600 BRAF mutants do not (XREF_SUPPLEMENTARY)."
26343582
reach
"In human islet cells, glucose and glucagon like peptide-1 activate the Rap and B-Raf signalling module, which mediates ERK activation in assays in vitro."
15995848
sparser
"Although the BRAF V600E -elicited activation of ERK has been demonstrated to contribute to TERT reactivation by maintaining an active chromatin state, it still remains to be addressed how activated ERK is selectively recruited to mutant TERT promoter."
33483600
reach
"KI BRAF paradoxically activates MEK and ERK to levels higher than those in cells with WT BRAF via heterodimerization with CRAF (Raf-1) [XREF_BIBR - XREF_BIBR]."
26623721
reach
"It was found that cell death induced by either PTPRkappa or KDELr-HV12 could be prevented by the co-expression of MEK1E, known to yield a constitutive ERK activation, or by BRAF that activates ERK mostly independently of CRAF."
30185827
sparser
"BRAF and MAPK activate extracellular signal-regulated kinase (ERK) downstream of the MAPK pathway and regulate cell proliferation [ xref ]."
35070538
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."
21540889
sparser
"Hence, Erk activation by B-Raf(V600E)/MEK, combined with suppression of its de-phosphorylation by MEDICA-induced ROS, may account for Erk hyper-activation, resulting in growth arrest and apoptosis of B-Raf(V600E) cancer cells."
26959890
reach
"Resistance to BRAF inhibitors develops relatively rapidly because of BRAF independent activation of MEK and ERK and other chemotherapeutic approaches will be necessary, both for melanomas lacking mutant BRAF and for melanomas that have developed resistance."
23658559
reach
"BRAF- and PTPN11 activating mutations, which drive MAPK/ERK pathway signaling , were enriched in rGBM that responded to PD-1 blockade."
35121903
reach
"XREF_BIBR Furthermore, both K-Ras and B-Raf could activate signal transduction route of MAPKs and ERK XREF_BIBR which, in turn, affected tumor progression through the regulation of cell survival, proliferation, and apoptosis."
25914533
reach
"Our data suggest that co-targeting ERK-signaling intermediates alongside KRAS(G12C) may prolong the benefit of therapy in the setting of emergent hotspot mutations in RAS or BRAF."
34759319
reach
"It has been shown that both KSR1 and B-Raf are feedback phosphorylation targets of ERK and that this process is enhanced by the docking of activated ERK."
23267331
reach
"Importantly, unlike BRAFV600E mutant cells, cells bearing BRAF in-frame deletions were resistant to the BRAF inhibitor vemurafenib [XREF_BIBR], suggesting a unique biochemical mechanism of ERK activation mediated by different mutations in BRAF."
28673397
reach
"This suggests that although mutated BRAF is the most prominent oncogene in melanoma, and acquiring an activating mutation in BRAF clearly seems to create an advantage in the propagation of melanocytic[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20350535
reach
"Examples of such events include activating mutations of the gene BRAF, which activate the MEK and ERK pathway?"
23720711
reach
"Mechanistically, BRAF and RAF1 operate independently to balance MAPK signaling : BRAF promotes ERK activation, while RAF1 dims stress kinase activation."
27431613
reach
"6 Unfortunately, first and second generation BRAFi can not be used as single agents to treat NRAS-mutant melanoma because while these inhibitors are effective at shutting down ERK signaling mediated by mutant-BRAF, they paradoxically upregulate ERK activity in the presence of oncogenic RAS, by stimulating BRAF-CRAF heterodimerization."
28717400
reach
"Very interestingly, one of the identified peptide is a transcription factors trigger cancer epithelial-mesenchymal transition, SLAIN 1 whose expression was modulated by BRAF mediated ERK activity in melanoma cells (23, 24)."
25437182
reach
"The MEK and ERK signaling pathway may be activated by BRAF in papillary thyroid cancer."
23000762
sparser
"BRAF (a proto-oncogene) encoding a Ser-Thr kinase protein which is a downstream effector protein in the RAS/RAF/ERK signaling pathway can directly phosphorylate the MEK and even activate the ERK to affect the cells proliferation and survival [ xref – xref ]."
28915704
reach
"In contrast, miR-524-5p overexpression inhibits the expression level of BRAF and ERK2 and suppresses MAPK and ERK activity, leading to reduced cell proliferation and migration events."
25275294
sparser
"► BRAF activates ERK but in some circumstances BRAF inhibitors can induce tumor growth ► BRAF inhibitors drive BRAF-CRAF binding, activating ERK in cells with oncogenic RAS ► Kinase-dead mutants of BRAF have the same effect as BRAF inhibitors ► Oncogenic RAS and kinase-dead BRAF cooperate to induce melanoma in mice"
20141835
reach
"Oncogenic BRAF V600E signals as an active monomer in the absence of active RAS, however, in many tumors BRAF dimers mediate ERK signaling."
32873792
reach
"Accordingly, inducible knockdown of ERK2, CRAF, and BRAF blocked ERK signaling rebound and reduced clonogenic growth after trametinib treatment (XREF_FIG and XREF_FIG)."
27338794
reach
"In PC12 cells, Ras and Raf causes transient activation of ERK, while Rap1 and B-Raf leads to sustained ERK signals [XREF_BIBR]."
20471282
sparser
"Strong ERK1/2 activation by oncogenic KRAS and BRAF does not repress activation of ERK5 in HEK293 cells."
26959608
reach
"MEK and ERK activation is normal in Raf-1-deficient cells and embryos, and is probably mediated by B-RAF."
11296228
reach
"BRAF is activated by RAS and subsequently activates ERK via MEK phosphorylation, thereby contributing to increased cell proliferation."
27471703
sparser
"Rap1-GTP is thought to activate ERK in a ras-independent manner by binding b-raf."
22695258
sparser
"In a non-cancer setting, BRAF activates kinases MEK and ERK, which in turn activate transcriptional machinery to promote differentiation, proliferation, growth and apoptosis [ xref ]."
29616301
sparser
"Activation of P-ERK by BRAF inhibitors in BRAF wild-type cells was more pronounced in cells with active RAS, either due to RAS mutation or to activation of RAS by upstream signaling components, such as RTKs."
21505228
sparser
"These included B-RAF which activates ERK via MEK1/2 directing cell proliferation, as well as MLK-like mitogen-activated protein triple kinase (MLTK) which can activate JNK-mediated pathway regulating actin organization, and has been shown to be an upstream MAP3K in stress induced by the ribotoxinsanisomycin, ricin and Shiga toxin ( xref ; xref )."
23352502
reach
"A recent study demonstrated that RKIP regulated Raf-1, but not B-Raf [29], suggesting that B-Raf can activate ERK independent of RKIP."
20688353
sparser
"Additionally, SB-590885, a B-RAF inhibitor activated ERK1/2 in human melanocytes ( xref )."
20818433
reach
"Therefore, in NK cells, SV does not appear to associate with actin, nor to play a role in activating signal transduction.It has been shown that smooth muscle archvillin (SmAV), an isoform of SV expres[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21070852
eidos
"Karasarides et al. ( 2004 ) showed that B-RAF depletion by siRNA blocked ERK activity , inhibited DNA synthesis , and induced apoptosis in three melanoma cell lines ."
15908010
reach
"Artificial Erk activation by expression of constitutively active Mek1 and B-Raf failed to block ephrin-A5 effects on growth cones, and inhibitors of the Erk pathway also failed to inhibit collapse by ephrin-A5."
18563700
reach
"The risk of cardiovascular adverse events from rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen activated extracellular signal regulated kinase (MEK) inhibitors is not fully characterized."
32418884
reach
"Numerous studies have linked the increased invasiveness of different cancers with the activation of ERK proteins, which is induced by C-RAF or BRAF, depending on the cellular context."
23435375
sparser
"Both in vitro and in vivo studies have demonstrated that BRAF-dependent phospho-ERK activation is a critical signaling event in HCL xref , xref , xref ."
29770206
reach
"Although it is clear that BRaf induces senescence in melanocytes by activating MEK and ERK, the downstream effectors of its cytostatic effect remain to be identified [XREF_BIBR, XREF_BIBR]."
22611400
reach
"BRAF V600E mutation leads to a constitutive active BRAF kinase independent of its upstream target, RAS, ultimately leading to increased ERK1/2 activation [XREF_BIBR]."
32759760
reach
"In cell lines made resistant to the BRAF inhibitor SB-590885, P-ERK was no longer suppressed by BRAF inhibition, suggesting activation of MEK-ERK signaling through another RAF isoform."
21505228
sparser
"The presence of a BRAF V600E mutation and activation of ERK, MEK, S6, and AKT were assessed with immunohistochemistry in 35 conjunctival nevi and 31 melanomas."
31247083
reach
"The BRAF activating aberrations, result in constitutive BRAF kinase activity, ERK signaling, proliferation and transformation [XREF_BIBR]."
27895815
reach
"The identification of BRAF driver mutations in melanoma has led to the development of specific inhibitors targeting the extracellular-signal-regulated kinase (ERK) pathway, which have high response rates and improve survival in patients with BRAF-mutant advanced melanoma and those at high risk of recurrence XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR."
30630828
reach
"BGB659 effectively inhibits ERK signaling driven by oncogenic BRAF dimers in tumor cells."
26343582
reach
"Similarly, furin has been identified as a pro-oncogenic driver of KRAS and/or BRAF-mediated ERK kinasepathway activation, which has been linked to the resistance of colorectal cancer to targeted therapies [89] ."
35406405
reach
"B-Raf and CRHR1 internalization mediate biphasic ERK1/2 activation by CRH in hippocampal HT22 Cells."
23371389
reach
"The increased apoptosis, observed in human melanoma cell lines when BRAF expression is downregulated using RNA interference, supports a role for oncogenic BRAF driven MEK and ERK overactivation in maintaining the transformed phenotype of malignant melanoma cells (Hingorani et al, 2003; Karasarides et al, 2004)."
16880785
reach
"The higher levels of ERK inhibition achieved in the BRAF mutated cell line, by RNAi, demonstrates that in these cells BRAF is the main activator of ERKs."
19878585
reach
"WT B-RAF, D593V B-RAF, and KD B-RAF, which do not activate ERK in COS cells, do not activate C-RAF."
15035987
reach
"(D594A) Braf lacks kinase activity but induces the related gene product Craf as well as the mitogen activated protein and extracellular signal regulated kinase (ERK) kinase (MEK)/ERK pathway."
20978199
reach
"This may provide an alternative pathway for EGF induced c-jun expression in bovine luteal cells.Taken together, we have demonstrated that EGF activates B-Raf and Raf-1, which subsequently activate the[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12644307
reach
"Blocking calcineurin activity in beta cells prevents dephosphorylation of B-Raf T401 and decreases B-Raf and ERK1/2 activities."
21135229
reach
"Inhibition of BRAF and MEK within the MAPK pathway did not inhibit ERK activation, which was in contrast partially inhibited by a direct ERK inhibitor."
28512266
reach
"Direct ERK1/2 inhibition is considered a promising approach to avoid ERK1/2 reactivation caused by upstream kinases BRAF, MEK1/2, and KRAS, as well as by receptor tyrosine kinase inhibitors, but the dynamics and selectivity of ERK1/2 inhibitors are much less studied compared to BRAF or MEK inhibitors."
35787369
reach
"Reduction of mutant B-RAF levels in melanoma cells via RNA interference decreased ERK activity and cell proliferation [XREF_BIBR]."
20161827
sparser
"Most papillary thyroid cancer expresses RET/PTC or BRAF mutants, which activate the MAPK pathway of MEK-ERK."
22750642
reach
"We find that the 50% induction of p61 WT BRAF driven ERK signaling by vemurafenib also occurs at approximately 100-300 nM."
26343582
sparser
"Thus, although C-RAF is not required for ERK activation by either the high or intermediate activity B-RAF mutants, the ability of impaired activity B-RAF mutants to stimulate ERK is dependent on C-RAF[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15035987
sparser
"BRAF600E -dependent activation of ERK leads to increased Mcl-1 stability upon the disruption of the S6K1-IRS-2/PI3K negative feedback by Everolimus."
27351224
reach
"BRAF activates ERK which in turn activates downstream transcription factors leading to cell differentiation, growth, proliferation and apoptosis 13."
27144064
reach
"Mechanisms involved include BRAF splice variants (16%) / BRAF gene amplification (13%), that increase levels of BRAF V600E homodimers, or secondary mutations in other genes involved in MAPK and ERK si[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29729495
reach
"Liu et al. showed that in BRAF V600E CRC models, TNO155, an SHP2 inhibitor, synergized with BRAF and MEK inhibitors by blocking ERK feedback activation by different RTKs."
36117524
reach
"They also showed that either BRAF or CRAF alone could trigger the level of ERK activation required for tumour maintenance."
28497782
reach
"Oncogenic RAS and BRAF that potently stimulate ERK signalling drive neoplasia of cutaneous melanocytes in zebrafish and are commonly mutated in human CM, but mutations are vanishingly rare in UM."
27166257
reach
"These results demonstrated that BTV-NS3 alters the localization of BRAF, which 197 may contribute to the BTV-activated MAPK/ERK pathway."
| DOI
sparser
"WT B-RAF, D593V B-RAF, and KD B-RAF, which do not activate ERK in COS cells, do not activate C-RAF (Figure 3B) ."
15035987
reach
"In this study, PTMScan experiment found that phosphorylations at residues Ser446 or Ser447 in B-Raf were dramatically increased over 1,000-fold in NFPAs, which clearly demonstrated that B-Raf was utmostly invoked in NFPAs to constantly abnormally activate ERK/MAPK pathway."
31920959
sparser
"Vemurafenib and Dabrafenib are selective inhibitors of BRAF V600E that potently inhibit MEK and ERK activation by BRAF V600E ( xref )."
31146260
reach
"Levels of only AURKB and WEE1 decreased in melanoma cells, when (V600E) B-RAF, mitogen activated protein kinase 1/2, or extracellular signal regulated kinase 1/2 protein levels were reduced using siRNA compared with other identified kinases."
23416158
reach
"Mutations in KRAS and/or BRAF that activate the ERK kinase are frequently found in colorectal cancer (CRC) and drive resistance to targeted therapies."
32139876
reach
"Thus formation of BRAF V600E/K homodimers is RAS dependent, but both BRAF V600E/K dimers and monomers can activate ERK signaling."
26343582