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BRAF phosphorylates MAP2K1. 72 / 85
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"After interacting with GTP-bound RAS proteins, B-Raf phosphorylates the proteins MEK1 and MEK2, activating molecules that lead to cell proliferation."
35554338
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"Brennan et al. hypothesize that regulatory B-Raf interacts with KSR2 in cis to introduce a conformational change in KSR2 thereby facilitating phosphorylation of MEK1 by an independent catalytic B-Raf [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30118796
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"BRAF directly phosphorylates the dual-specificity kinases MEK1 and MEK2, which in turn phosphorylate and activate the mitogen activated protein kinases, ERK1 and ERK2."
23477830
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"Recent work, however, indicates that KSR1 [127] and KSR2 [128] possess catalytic activity, which is necessary for their function.Brennan et al. reported that the human KSR2 scaffold participates in th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22569528
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"Brennan et al. reported that the human KSR2 scaffold participates in the assembly of a MEK1/KSR2/B-Raf ternary complex that is responsible for promoting rabbit MEK1 phosphorylation by mouse B-Raf."
22569528
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"BRAF protein is phosphorylated and activated, and BRAF in turn phosphorylates MEK1/MEK2, which activates ERK and promotes its entry into the nucleus to regulate gene expression."
30809081
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"BRAF, also known as serine/threonine-protein kinase B-Raf, can phosphorylate MAP2K1 and thereby activates the MAP kinase signal transduction pathway in living cells."
33240890
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"Brennan et al. hypothesize that regulatory B-Raf interacts with KSR2 in cis to induce a conformational change in KSR2 thereby facilitating phosphorylation of MEK1 by an independent catalytic B-Raf mol[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22569528
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"We confirmed that B-Raf activated by cAMP phosphorylates the sites in MEK-1 (serines 218 and 222) that have previously been shown to be required for MEK activation by Raf-1 ( Alessi et al. 1994 )."
9094716
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"BRAF directly phosphorylates the dual-specificity kinases MEK1 and MEK2, which in turn phosphorylate and activate the mitogen-activated protein kinases, ERK1 and ERK2."
23477830
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"Activated BRAF proteins phosphorylates and activates MEK1 and 2 (MAPKKs), which in turn phosphorylate and activate ERK1 and 2 (MAPKs)."
19383316
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"Similar to the endogenous MEK1/2 phosphorylation in HEK293 cells, in vitro immunoprecipitated phosphomimetic BRAF S732E phosphorylated MEK1 less relative to the phospho-deficient A mutant ( xref , H and I )."
37625591
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"BRAF has the highest capacity among the other RAF family proteins, ARAF and CRAF, to phosphorylate MEK (MEK1 and MEK2) [16]."
37834222
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"BRAF phosphorylates and activates Mitogen-activated protein kinase kinase 1 (MEK1) and MEK2, which in turn phosphorylate and activate ERK1/2, stimulating the MAPK pathway and ultimately promoting tumor growth."
38357312
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"6 Compound 1 was equally potent toward both wild-type and mutant B-Raf in the biochemical assays where phosphorylation of MEK1 by the B-Raf proteins were measured (IC 50 = 2 nM, Table 1 )."
27085672
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"Under normal circumstances, BRAF phosphorylates the MAPKs MEK1 and MEK2, which activate downstream signaling."
27058947
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"In response to epidermal growth factor, nerve growth factor, and platelet-derived growth factor, B-Raf and Raf-1 are activated, phosphorylate recombinant kinase-inactive MEK-1, and activate wild-type MEK-1."
7935374
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"Activated BRAF proteins phosphorylates and activates MEK1 and 2 (MAPKKs), which in turn phosphorylate and activate ERK1 and 2 (MAPKs)."
19383316
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"Recent studies have suggested that KSR1 and 2 possess catalytic activity and that KSR2 participates in the assembly of a MEK1/KSR2/B-Raf ternary complex that is responsible for promoting rabbit MEK1 phosphorylation by mouse B-Raf ( xref , xref )."
28440493
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"Active BRAF phosphorylates MEK1 and MEK2 kinases, leading to ERK1 and ERK2 activation."
37634281
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"In response to epidermal growth factor, nerve growth factor, and platelet derived growth factor, B-Raf and Raf-1 are activated, phosphorylate recombinant kinase-inactive MEK-1, and activate wild-type MEK-1."
7935374
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"The data obtained by the biosensor experiments suggest that BRAF-phosphorylated MEK1 along with the MEK1 -S218D/S222D KinCon reporters occupy an active and opened kinase conformation, which is in accordance with the shown structural MD simulation data."
33808483
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"We envisioned two models for how MEK1 binding to KSR1 potentiates the ability of KSR1 to promote BRAF phosphorylation of MEK1."
29433126
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"Subsequent to auto-phosphorylation, fully activated BRAF phosphorylates MEK1 to relay downstream signal."
29992710
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"The direct phosphorylation of MEK1 by KSR1, however, appears to be a low probability event compared to MEK1 phosphorylation by B-Raf."
35508574
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"MEK1 phosphorylation by BRAF was tested in presence of purified anti BRAF autoantibodies from RA patients."
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"MEK1 from this Raf/KSR1/MEK1 ternary scaffolding unit is then translocated to an active B-Raf dimer and phosphorylated by B-Raf from the dimer [48, 57]."
35508574
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"MEK1 and MEK2 are normally phosphorylated by BRAF and go on to activate downstream components of the mitogen-activated protein kinase pathway."
23994118
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"These investigators reported that the KSR2 scaffold assembles a MEK1–KSR2–B-Raf ternary complex that is responsible for promoting MEK1 phosphorylation by B-Raf."
30118796
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"When BRAF is inhibited, ERK can still be activated through CRAF, and BRAF binds to and phosphorylates MEK1 and MEK2 more efficiently than CRAF [XREF_BIBR], especially in his V600E/K mutated form."
33507915
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"HMGCL, however, selectively promotes BRAF V600E dependent phosphorylation and activation of MEK1 by controlling intracellular levels of its product AA, which specifically promotes BRAF V600E (but not BRAF WT) binding to MEK1 and subsequent MEK1 phosphorylation in cancer cells."
26145173
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"BRAF is a critical kinase in the Ras/Raf/MEK/ERK cascade, phosphorylates MAP2K1, and activates the MAPK signal transduction pathway, involving the transduction of mitogenic signals from the cell membrane to the nucleus [69]."
37920504
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"The KSR2 scaffold assembles MEK1–KSR2–B-RAF ternary complexes responsible for promoting MEK1 phosphorylation by B-RAF."
22177953
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"These investigators hypothesize that regulatory B-RAF interacts with KSR2 in cis to induce a conformational change in KSR2 thereby facilitating phosphorylation of MEK1 by an independent catalytic B-RA[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22177953
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"The KSR2 scaffold assembles MEK1–KSR2–B-RAF ternary complexes responsible for promoting MEK1 phosphorylation by B-RAF."
22177953
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"We found that not BRAF WT but BRAF V600E dependent phosphorylation of MEK1 was increased in the presence of AA ( xref )."
26145173
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"Although both BRAF V600E or BRAF WT phosphorylates MBP but such phosphorylation was not affected in the presence of increasing concentrations of acetoacetate or 3-HB ( xref and xref ), suggesting that acetoacetate may specifically affect BRAF V600E dependent phosphorylation of MEK1."
26145173
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"MEK1 and 2 are phosphorylated and activated by B-RAF and a P124L mutation in MEK1 was identified through a MEK1 random mutagenesis screen that confers cellular resistance to the MEK inhibitor, AZD6244."
21593776
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"MEK1 phosphorylation by BRAF was tested in the presence of purified anti-BRAF autoantibodies from RA patients or control antibody."
20955560
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"Activated B-raf can then phosphorylate the dual-specificity kinases MEK1 and MEK2, which in turn activate ERK."
16996249
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"Autoantibodies to BRAF activate the phosphorylation of MEK1 by BRAF."
20955560
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"Phosphorylation of MEK1 by BRAF was detected by Western blotting and quantified."
20955560
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"MEK1 and MEK2 are normally phosphorylated by BRAF and go on to activate downstream components of the mitogen activated protein kinase pathway."
25037456
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"The results is the activated BRAF kinase domain, which phosphorylates MEK1, the downstream member of the MAPK signaling pathway [101]."
38953007
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"We observed that 65% of anti-BRAF autoantibodies activate phosphorylation of MEK1 by BRAF in vitro."
20955560
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"However, in substrate phosphorylation assays, trametiglue not only inhibited MEK1 and MEK2, but also upstream kinases, including inhibition of both BRAF and CRAF phosphorylation of MEK1 as substrate ( xref , bottom)."
32927473
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"BRAF phosphorylates MEK1 and/or MEK2, which in turn activates ERK1 and/or ERK2."
31723831
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"MEK1 phosphorylation by BRAF was tested in the presence of purified anti-BRAF autoantibodies from RA patients or control antibody."
20955560
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"Autoantibodies to BRAF activate the phosphorylation of MEK1 by BRAF."
20955560
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"Both B-Raf-WT and B-Raf-ΔN phosphorylate MEK1 robustly, and for both, the deletion of the distal tail segment resulted in substantially lower levels of MEK1 phosphorylation, while the binding of ΔDTS mutants to 14-3-3 is unaffected ( xref , xref , xref and xref )."
31604311
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"Phosphorylation of MEK1 by BRAF was detected by Western blotting and quantified."
20955560
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"The most common molecular aberration in these tumors is the activation of the BRAF oncogene, either via a KIAA1549::BRAF fusion or a BRAF p.V600E mutation, which in turn phosphorylates downstream targets MEK1 and MEK2 of the MAPK pathway (13)."
37519792
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"We observed that 65% of anti-BRAF autoantibodies activate phosphorylation of MEK1 by BRAF in vitro ."
20955560
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"MEK1 phosphorylation by BRAF was tested in presence of purified anti BRAF autoantibodies from RA patients."
22349616
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"MEK1 and MEK2 are normally phosphorylated by BRAF and go on to activate downstream components of the mitogen-activated protein kinase pathway."
25037456
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"BRAF, also known as serine/threonine protein kinase B-Raf, can phosphorylate MAP2K1 and thereby activates the MAP kinase signal transduction pathway in living cells."
33240890
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"After RAS engagement, RAF protein kinases RAF1, B-RAF, and A-RAF are activated and phosphorylate their dual-specificity protein kinase substrates MEK1 and MEK2 (also known as MAP2K1 and MAP2K2) [ xref ]."
30974877
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"The direct phosphorylation of MEK1 by KSR1, however, appears to be a low probability event compared to MEK1 phosphorylation by B-Raf."
35508574
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"When BRAF is inhibited, ERK can still be activated through CRAF, and BRAF binds to and phosphorylates MEK1 and MEK2 more efficiently than CRAF [ xref ], especially in his V600E/K mutated form."
33507915
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"Under normal circumstances, BRAF phosphorylates the MAPKs MEK1 and MEK2, which activate downstream signaling."
27058947
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"Our proposed mechanism for B-Raf phosphorylation of MEK1 aligns well with previous descriptions of MEK1 activation based on in vitro and in vivo experiments [ xref , xref , xref , xref ]."
35508574
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"Furthermore, the decreased expression of kinase suppressor Ras 2 (KSR2) and RAS guanyl-releasing protein 1 (RASGRP1), which promotes BRAF-mediated phosphorylation of MAP2K1/MEK1 and helps in the activation of Ras, would also contribute to the inhibition of cell proliferation."
37834191
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"Using the same experimental approach, we leveraged the ~ 350-bp CRAF fragment library to identify the core binding site of MEK1, a downstream kinase that is phosphorylated by the RAF paralogs ARAF, BRAF, and CRAF."
33410398
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"In striking contrast, direct serine S218/222 phosphorylation and activation of MEK1 by recombinant B-Raf does not require serine 298 phosphorylation or MEK1 catalytic activity ( Fig. 5 b)."
17314031
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"These investigators hypothesize that regulatory B-RAF interacts with KSR2 in cis to induce a conformational change in KSR2 thereby facilitating phosphorylation of MEK1 by an independent catalytic B-RA[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22177953
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"Fur- thermore, NGF treatment increases B-Raf autokinase activity but this is inhibited by cAME Importantly, in a reconstitution assay, B-Raf can phosphorylate and activate MEK-1."
7835430
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"MEK1 and MEK2 are normally phosphorylated by BRAF and go on to activate downstream components of the mitogen activated protein kinase pathway."
23994118
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"Fur- thermore, NGF treatment increases B-Raf autokinase activity but this is inhibited by cAME Importantly, in a reconstitution assay, B-Raf can phosphorylate and activate MEK-1."
7835430
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"BRAF proteins, Ras regulated kinase, phosphorylate MEK1 and MEK2, which in turn phosphorylate MAPK-ERK 1/2."
16404419
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"Immunoprecipitated BRAF(V600E) phosphorylated MEK1 protein in vitro ( xref , lane 5), however, treatment with 17-DMAG clearly inactivated the kinase activity of BRAF(V600E) ( xref , lane 6), even though equivalent levels of BRAF(V600E) protein were utilized from treated and non-treated cell lysates ( xref , lanes 3 and 4)."
18676857
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"In the context of melanoma, oncogenic BRAF V600E constitutively phosphorylates and activates the MEK1 and MEK2 kinases, which in turn phosphorylate and activate the ERK1 and ERK2 kinases, hyperactivating the canonical Mitogen Activated Protein Kinase Pathway (MAPK) to promote uncontrolled melanocytes growth and caner initiation and progression xref ."
31317143
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"These investigators reported that the KSR2 scaffold assembles a MEK1–KSR2–B-Raf ternary complex that is responsible for promoting MEK1 phosphorylation by B-Raf."
30118796