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RAF1 phosphorylates MAP2K1. 86 / 92
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"Once activated, Raf-1 phosphorylates the MAPK kinases MEK1 and MEK2, that finally stimulate ERK1 and ERK2."
25432084
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"The site of action of baicalein is assumed to be the phosphorylation of MEK-1 by Raf-1, since the activity of Raf-1, but not MEK-1, was clearly inhibited by baicalein."
12568909
rlimsp
"In this report, we demonstrate a novel single step assay for Raf-1 kinase activity based on phosphorylation of recombinant MEK-1, detected using an activation-specific MEK antibody that recognizes MEK only when specifically phosphorylated by Raf-1 on Ser 217 and Ser 221."
11042690
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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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"XREF_BIBR Once activated, Raf-1 phosphorylates the MAPKs MEK1 and MEK2, that finally stimulate ERK1 and ERK2."
28176948
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"Active Raf-1 phosphorylates and stimulates a dual specificity kinase MEK1, which in turn phosphorylates and activates ERKs."
9094715
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"The autoradiograph in Fig. 1 C shows a typical experiment of MEK-1 phosphorylation by immunoprecipitated Raf-1 followed by the in vitro kinase assay of GST[K97A] substrate."
9484913
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"As shown in Figure 7 D, the expression of MEK-1 phosphorylation caused by Raf1 kinase was concentration-dependently downregulated by luteolin in a cell-free system, confirming that luteolin is a Raf1 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29883707
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"In C, upper and middle panels, Raf-1 phosphorylated both Mek1 (lane 1) and ALG-2 (lane 2), and did not phosphorylate the sample from empty vector control (lane 3) and IgG (lane 4)."
15925322
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"Raf-1 phosphorylates and activates MEK1, which in turn phosphorylates MAPK."
22830400
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"Their data indicate that MEK1 phosphorylation mediated by C-Raf requires KSR1 catalytic activity."
26207888
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"Phosphorylation of MKK1 by Raf-1 correlated with activation and reached a plateau of approximately 2 mol and mol."
7945229
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"PKC is known to phosphorylate and activate c-Raf (), and the activated c-Raf may further phosphorylate and activate MEK1 catalyzing ERK phosphorylation."
12925217
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"Further investigations showed that cisplatin directly binds to cysteine 142 site of MEK1, restricting its access to C-RAF that typically phosphorylates MEK1."
31612108
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"Down stream of PKA, the activity of B-Raf was significantly decreased by nicotine in SH-SY5Y cells, as determined by direct measurement of MEK1 phosphorylation or in vitro kinase assays, whereas the modulation of MEK1 phosphorylation by Raf-1 tended to increase."
11905997
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"Baicalein inhibited the phosphorylation of exogenous MEK-1 by Raf-1 under cell-free conditions, while it did not change the phosphorylation of exogenous p42 MAPK by MEK-1."
12568909
sparser
"The same MKK6-C28 peptide failed to inhibit the activating phosphorylation of MEK1 by Raf-1 ( Figure 6 G)."
15866172
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"The same MKK6-C28 peptide failed to inhibit the activating phosphorylation of MEK1 by Raf-1."
15866172
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"The site of action of baicalein is assumed to be the phosphorylation of MEK-1 by Raf-1, since the activity of Raf-1, but not MEK-1, was clearly inhibited by baicalein (Fig. 6) [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12568909
sparser
"Raf-1 phosphorylated MKK1 on one major tryptic phosphopeptide, the phosphorylation of which increased with time."
7945229
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"In the ERK1/2 cascade, growth-factor-derived extracellular signals are translated to Raf-1 activation, which leads to the phosphorylation of MEK1 and MEK2, which in turn phosphorylate and activate ERK[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
11684438
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"The differences in inhibitor binding affinity provide direct evidence that unphosphorylated and RAF1-phosphorylated MEK1 form distinct inhibitor sites."
21793567
sparser
"Raf-1 phosphorylates and activates the MAPKKs, MEK-1 and MEK-2, which phosphorylate the Thr and Tyr residues of Erk1/2."
22481092
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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
rlimsp
"These changes regulate the ability of Raf-1 to phosphorylate its downstream targets MEK1 and MEK2."
11948406
sparser
"Raf-1 phosphorylates and activates MEK1, which in turn phosphorylates MAPK."
22830400
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"These receptors activate the small molecule GTPase Ras, which activates Raf1, which in turn phosphorylates and activates MAPK and ERK kinase 1 and 2 (MEK1/2) [XREF_BIBR] (XREF_FIG)."
20363322
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"Raf-1 subsequently phosphorylates and activates the downstream kinase MAPK kinase MEK1, the direct activator of ERK proteins [76]."
17530222
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"Raf-1 phosphorylates MEK1 and MEK2 to activate ERK1 and ERK2, controlling gene expression involved in cell division, differentiation, migration, and apoptosis."
20833246
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"To rule out the possibility that SB203580 activated Raf-1 phosphorylated the recombinant MEK1 in vitro on sites other than those required for MEK activation, we performed a coupled assay."
10037150
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"5~ Activated raf phosphorylates and activates MEK-1 (__MAP or ERK _Kinase) which in turn phosphorylates and activates members of the MAP kinase family (also known as Extracellular Signal Regulated [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
8748142
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"Phosphorylation of MKK1 by Raf-1 correlated with activation and reached a plateau of approximately 2 mol/mol."
7945229
sparser
"Once fully activated, Raf-1 phosphorylates and activates MKK1 or MKK2 (also called MEK1/2)."
18752467
trips
"Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK)."
10490027
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"Raf1 upon binding to Ras becomes active and phosphorylates the MAP kinase kinase MEK1 and MEK2."
15110179
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"Activation of Ras results in sequential activation of Raf1, which in turn phosphorylates and activates MEK 1 and 2."
26262615
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"When activated in this manner, Raf-1 in turn phosphorylates MEK-1 and -2."
11897507
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"4 Activated RAF1 phosphorylates the protein kinases MEK1 and MEK2, which activate the mitogen-activated protein kinase (MAPK) cascade, ultimately resulting in nuclear transloca[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
11905614
sparser
"Raf-1 phosphorylates MEK1 and MEK2 to activate ERK1 and ERK2, controlling gene expression involved in cell division, differentiation, migration, and apoptosis."
20833246
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"Finally, we investigated the molecular mechanism of JSAP1's inhibitory function and showed that JSAP1 prevents MEK1 phosphorylation and activation by Raf-1, resulting in the suppression of the activation of ERK."
11044439
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"The phosphorylation of MEK1 and MEK2 could be stimulated by RAF1, which in turn activates the ERK1 and ERK2 to control cell cycle, apoptosis, and cell migration [34, 35]."
35341155
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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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"Raf-1 subsequently phosphorylates and activates the downstream kinase MAPK kinase MEK1, the direct activator of ERK proteins [76]."
17530222
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"In conclusion, we show for the first time that baicalein, a flavonoid of natural origin, inhibits the ERK/MAPK cascade and prostaglandin synthesis, acting on the phosphorylation of MEK-1 by Raf-1."
12568909
sparser
"These results imply that baicalein inhibits the ERK/MAPK cascade, acting on the phosphorylation of MEK-1 by Raf-1."
12568909
sparser
"The results obtained suggest that baicalein inhibits the ERK/MAPK cascade by acting on the phosphorylation of MEK-1 by Raf-1."
12568909
sparser
"Once fully activated, Raf-1 phosphorylates and activates MKK1 or MKK2."
27848025
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"This activation is mediated by activated MEK1, which in turn is phosphorylated by RAF-1, and RAF-1 is activated by RAS (for reviews see xref ; xref ; xref )."
14997206
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"We titrated the amount of the Raf-1 used in the assay so that in the absence of KSR, Raf-1 autophosphorylation and Raf-1-dependent MEK1 (K97M-MKK1) phosphorylation were not detectable (not shown)."
9094715
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"Raf-1 phosphorylated MKK1 on one major tryptic phosphopeptide, the phosphorylation of which increased with time."
7945229
rlimsp
"RKIP inhibits the phosphorylation of MAP/extracellular signal-regulated kinase 1 (MEK1) by Raf-1 by disrupting the interaction between these two kinases."
11585904
rlimsp
"Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK)."
10490027
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"8,10 Once activated, Raf-1 phosphorylates two mitogen-activated protein kinases, MEK 1 and MEK 2 , which in turn phosphorylate the mitogen-activated protein kinases extracellular signal-regulated ki[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
14613029
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"Although we observed several new C-Raf phosphorylation sites in the MEK-1 coexpressing cells (XREF_FIG, panel 9, spots n, x, y and z), these sites accounted only for a small fraction of the overall C-Raf phosphorylation."
23360980
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"Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK)."
10490027
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"The results explicitly confirmed that phosphorylation of MEK1 by FLAG-CRAF was, indeed, enhanced in the presence of GSTP1 relative to that in its absence ( xref )."
32719131
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"Activated Raf-1 then phosphorylates the protein kinases MEK1 and MEK2, which in turn activate mitogen-activated protein kinase/ extracellular signal-related kinase (MAPK/ERK), a sequence of events that results in the transcription of target genes that are involved in cell proliferation [ xref ]."
15535857
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"Activated Raf-1 can phosphorylate MEK1 and MEK2, which in turn activate ERK1 and ERK2."
22412974
sparser
"The inhibition of the RAF1 kinase activity by PEBP1 impairs the activating MEK1 phosphorylation by RAF1 [ xref , xref ]."
35203304
trips
"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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"In unstimulated cells, Raf kinase inhibitor protein (RKIP) is bound to Raf, thus preventing the phosphorylation of MEK1 by Raf-1 and blocking the Ras-Raf-MEK-extracellular signal related kinase (ERK) [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25104559
biopax:netpath
No evidence text available
9484913
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"These findings may be explained by the previous findings that Rac1 and Cdc42 can interact with Raf-1 in a synergistic manner to activate ERK via pathways that involve phosphorylation of both MEK1 by PAK1 and Raf-1 by PAK-3 [XREF_BIBR, XREF_BIBR]."
26588713
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"Once activated, Raf-1 can phosphorylate and thereby activate the dual specificity protein kinases MEK1 and MEK2, which in turn phosphorylate and activate the serine/threonine protein kinases ERK1 and ERK2 [XREF_BIBR]."
20473784
sparser
"When activated in this manner, Raf-1 in turn phosphorylates MEK-1 and -2."
11897507
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"Each of these pathways contains a series of biochemical reactions between proteins and biomolecules, such as a phosphorylation reaction (" RAF1 phosphorylates MEK1 ") where one protein adds a phosphate group to another, changing the protein 's state."
26361499
sparser
"Baicalein inhibited the phosphorylation of exogenous MEK-1 by Raf-1 under cell-free conditions, while it did not change the phosphorylation of exogenous p42 MAPK by MEK-1."
12568909
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"Another factor is that phosphorylation of MEK1 by cRAF results in reduced affinity of MEK 1/2 allosteric inhibitors [XREF_BIBR; XREF_BIBR]."
26284568
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"Hu et al. have recently shown that MEK1 phosphorylation by KSR1 and C-Raf heterodimers requires KSR activity and cooperation with C-Raf [XREF_BIBR]."
23455463
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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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"Raf-1, in turn, phosphorylates MEK1 and MEK2 on Ser217/218 and Ser221 residues, respectively."
32471307
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"Our results show that RKIP inhibited RAF1 mediated phosphorylation of MEK1, but did not affect MEKK1 mediated phosphorylation of MEK1 (XREF_FIG A)."
12695496
rlimsp
"Finally, we investigated the molecular mechanism of JSAP1's inhibitory function and showed that JSAP1 prevents MEK1 phosphorylation and activation by Raf-1, resulting in the suppression of the activation of ERK."
11044439
sparser
"Thus, baicalein is assumed to be an inhibitor of the phosphorylation of MEK-1 by Raf-1."
12568909
sparser
"Another factor is that phosphorylation of MEK1 by cRAF results in reduced affinity of MEK 1/2 allosteric inhibitors [ xref ; xref ]."
26284568
sparser
"As shown in D, the expression of MEK-1 phosphorylation caused by Raf1 kinase was concentration-dependently downregulated by luteolin in a cell-free system, confirming that luteolin is a Raf1 inhibitor[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29883707
reach
"PKC is known to phosphorylate and activate c-Raf (Kolch et al, 1993), and the activated c-Raf may further phosphorylate and activate MEK1 catalyzing ERK phosphorylation."
12925217
sparser
"Raf-1 subsequently phosphorylates MAPKK, MEK1 and MEK2 (MEK1/2), which in turn phosphorylate ERK1/2 threonine and tyrosine residues at its activation loop."
19857199
sparser
"Down stream of PKA, the activity of B-Raf was significantly decreased by nicotine in SH-SY5Y cells, as determined by direct measurement of MEK1 phosphorylation or in vitro kinase assays, whereas the modulation of MEK1 phosphorylation by Raf-1 tended to increase."
11905997
reach
"Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK)."
10490027
reach
"Active Raf-1 phosphorylates and stimulates a dual specificity kinase MEK1, which in turn phosphorylates and activates ERKs."
9094715
rlimsp
"This could be partly explained by the inability of Raf-1 to phosphorylate MKK1 C-terminal deletion mutants even though the phosphorylation sites were intact in these mutants."
11604401
sparser
"To rule out the possibility that SB203580-activated Raf-1 phosphorylated the recombinant MEK1 in vitro on sites other than those required for MEK activation, we performed a coupled assay."
10037150
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"This activation is mediated by activated MEK1, which in turn is phosphorylated by RAF-1, and RAF-1 is activated by RAS (for reviews see Cobb, 1999; Widmann et al, 1999; Chang and Karin, 2001)."
14997206
sparser
"Once activated, Raf-1 phosphorylates the MAPK kinases MEK1 and MEK2, that finally stimulate ERK1 and ERK2."
25432084
rlimsp
"Phosphopeptide maps suggest a single Raf-1 phosphorylation site on mek1."
8248196