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

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Statements

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phosphosite cbn pc11 biopax bel_lc signor biogrid tas lincs_drug hprd trrust | geneways tees isi trips rlimsp medscan sparser reach
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RAF1 phosphorylates MAP2K1. 9 / 96
27 | 2 7 34 20
sparser
"The results obtained suggest that baicalein inhibits the ERK/MAPK cascade by acting on the phosphorylation of MEK-1 by Raf-1."
biopax:inoh
No evidence text available
biopax:inoh
No evidence text available
reach
"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]."
reach
"Once activated, Raf-1 phosphorylates the MAPK kinases MEK1 and MEK2, that finally stimulate ERK1 and ERK2."
rlimsp
"These changes regulate the ability of Raf-1 to phosphorylate its downstream targets MEK1 and MEK2."
reach
"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]."
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."
sparser
"When activated in this manner, Raf-1 in turn phosphorylates MEK-1 and -2."
RAF1 phosphorylates MAP2K1 on S218. 10 / 23
1 10 1 5 | 5 1
biopax:pid
No evidence text available
biopax:netpath
No evidence text available
rlimsp
"RAF1 is known to phosphorylate MEK1 at serines 218 and 222 and the extent of this double phosphorylation is a reliable indicator of RAF1 activity (Bondzi et al., 2000)."
hprd
No evidence text available
rlimsp
"Activation of MEK1 by MEKK-C is accompanied by phosphorylation of S218 and S222, which are also phosphorylated by the protein kinases c-Mos and Raf-1."
biopax:pid
No evidence text available
biopax:netpath
No evidence text available
rlimsp
"Phosphopeptide analysis demonstrated that serine residues 218 and 222 of human MEK1 are the primary sites for phosphorylation by c-raf."
biopax:pid
No evidence text available
hprd
No evidence text available
RAF1 phosphorylates MAP2K1 on S222. 10 / 18
1 10 1 4 | 1 1
biopax:phosphositeplus
No evidence text available
rlimsp
"This strategy revealed that MEK1 is constitutively and mainly phosphorylated at the Thr-292, Ser-298, Thr-386, and Thr-388 residues in vivo, and that combinations of phosphorylations at these four residues produce at least six phosphorylated variants of MEK1. Like the levels of phosphorylation of the Ser-218 and Ser-222 residues by RAF1, which have been well studied, the phosphorylation statuses of Thr-292, Ser-298, Thr-386, and Thr-388 residues vary widely during activation and deactivation of the MAPK pathway."
signor
"Among other effectors, active ras binds and activates the raf kinase, iniziating a kinase cascade involving serine phosporylation of mek1/2 (mapkk) and tyrosine and threonine phosphorylation of erk1/2 ras activation leads to raf and subsequently mek activation. Phospholipide analysis demostrated that serine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf."
biopax:pid
No evidence text available
biopax:pid
No evidence text available
biopax:pid
No evidence text available
reach
"Raf-1 phosphorylates MEK1 on two serine residues, Ser 218 and Ser222 [XREF_BIBR] MEK1 phosphorylates tyrosine and threonine residues in the ERK activation loop."
hprd
No evidence text available
biopax:pid
No evidence text available
hprd
No evidence text available
RAF1 phosphorylated on S621 and T268 phosphorylates MAP2K1 on S222. 4 / 4
4 |
biopax:pid
No evidence text available
biopax:pid
No evidence text available
biopax:pid
No evidence text available
biopax:pid
No evidence text available
RAF1 phosphorylated on S621 and T268 phosphorylates MAP2K1 on S218. 4 / 4
4 |
biopax:pid
No evidence text available
biopax:pid
No evidence text available
biopax:pid
No evidence text available
biopax:pid
No evidence text available
RAF1 phosphorylates MAP2K1 on serine. 3 / 3
| 1 1 1
reach
"Raf-1 phosphorylates MEK1 on two serine residues, Ser 218 and Ser222 [XREF_BIBR] MEK1 phosphorylates tyrosine and threonine residues in the ERK activation loop."
rlimsp
"Raf-1 forms a stable complex with Mek1 and activates Mek1 by serine phosphorylation."
sparser
"After activation of EGFR signaling, key downstream steps involve phosphorylation by RAF1 kinase of two distinct serine residues on both MEK1 and MEK2 ( xref )."
Kinase-active RAF1 phosphorylates MAP2K1 on serine. 3 / 3
3 |
bel
"Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK)"
bel
"Despite remarkable progress in dissecting the signaling pathways that are crucial for the metabolic effects of insulin, the molecular basis for the specificity of its cellular actions is not fully understood. One clue might lie in the spatial and temporal aspects of signaling. Recent evidence suggests that signaling molecules and pathways are localized to discrete compartments in cells by specific protein interactions. Also, the rapid termination of tyrosine or lipid phosphorylation by phosphatases or serine kinases might tightly control the strength of a signaling pathway, thus determining its effect on growth, differentiation and metabolism. Insulin is the most potent anabolic hormone known, promoting the synthesis and storage of carbohydrates, lipids and proteins and inhibiting their degradation and release back into the circulation. Decreased secretion of insulin, coupled with resistance to its actions, results in type 2 diabetes, a devastating disease that is reaching epidemic proportions [1]. Even in the absence of diabetes, insulin resistance is often associated with central obesity, hypertension, polycystic ovarian syndrome, dyslipidemia and atherosclerosis. At the cellular level, insulin action is characterized by diverse effects, including changes in vesicle trafficking, stimulation of protein kinases and phosphatases, promotion of cellular growth and differentiation and activation or repression of transcription. This complexity suggests that insulin action must involve multiple signaling pathways that diverge at or near the activation of its tyrosine kinase receptor. In fact, it is likely that even individual effects of the hormone require multiple signaling inputs. Evidence is emerging that the coordination of these pathways might be governed by their intracellular compartmentalization or duration of action. Here, we consider how temporal and spatial aspects of signal transduction play a crucial role in determining the specificity of insulin action, focusing on signal initiation from the receptor that is spatially segregated into discrete domains of the plasma membrane, as well as the mechanisms that determine the duration of individual signaling pathways. Together, these factors help to differentiate insulin from other hormones that share some of the same overall signaling properties. Divergent signaling pathways are initiated by insulin receptor substrates. The insulin receptor is a tyrosine kinase that catalyzes the phosphorylation of several intracellular substrates, including the insulin receptor substrate (IRS) proteins [2], GAB-1 [3], Shc [4], APS [5], p60DOK [6], SIRPS [7] and c-Cbl [8] (Fig. 1). Each of these substrates recruits a distinct subset of signaling proteins containing Src homology 2 (SH2) domains, which interact specifically with sequences surrounding the phosphotyrosine residue. Moreover, each of these substrates can be confined to distinct locations in the cell by specific sequences that direct interactions with other proteins or lipids. Most attention in the field of insulin receptor substrates has focused on the IRS family of proteins. Mice lacking the IRS-1 protein are insulin resistant but do not develop overt diabetes [9,10]. By contrast, animals lacking IRS-2 exhibit both impaired glucose tolerance and diabetes [11], which appears to result from a defect in insulin secretion as well as insulin resistance, presumably owing to decreased b-cell proliferation in the pancreas in the face of increased demand for insulin. Despite the similarity in structure and function, the apparent differences in phenotype between IRS1 and IRS2 knockout mice underscore a specific signaling specificity that probably results from their tissue distribution, subcellular location, activation–inactivation kinetics and combinatorial interactions with downstream effectors [12]. The tyrosine phosphorylation of IRS family members generates docking sites for sev..."
bel
"Protein kinase C (PKC) regulates activation of the Raf-1 signaling cascade by growth factors, but the mechanism by which this occurs has not been elucidated. Here we report that one mechanism involves dissociation of Raf kinase inhibitory protein (RKIP) from Raf-1. Classic and atypical but not novel PKC isoforms phosphorylate RKIP at serine 153 (Ser-153). RKIP Ser-153 phosphorylation by PKC either in vitro or in response to 12-O-tetradecanoylphorbol-13-acetate or epidermal growth factor causes release of RKIP from Raf-1"
RAF1 phosphorylated on T269 and S338 phosphorylates MAP2K1 on S222. 2 / 2
2 |
biopax:pid
No evidence text available
biopax:pid
No evidence text available
RAF1 phosphorylated on T268 phosphorylates MAP2K1 on S222. 2 / 2
2 |
biopax:pid
No evidence text available
biopax:pid
No evidence text available
RAF1 phosphorylated on S338 phosphorylates MAP2K1 on S222. 2 / 2
2 |
biopax:pid
No evidence text available
biopax:pid
No evidence text available
Kinase-active RAF1 phosphorylates MAP2K1 on S218. 2 / 2
2 |
bel
"Western blot analysis was performed on protein extracts isolated from HPECs overexpressing Cdc37 or the vector only (Fig. 1C) ? .Raf-1 steady-state levels were unchanged. However, Raf-1 activity, measured by the abundance of phosphorylated S217/221 MEK1/2, a direct target of Raf-1 (30) , was consistently elevated in Cdc37-overexpressing cells, whereas total MEK1/2 levels were unchanged. Increases in Cdk4 levels and markedly reduced p16 expression were also consistently observed in Cdc37-overexpressing HPECs. "
bel
"c-Raf activates MEK1 by phosphorylating at serine residues 218 and 222 (30–32)."
Kinase-active RAF1 leads to the phosphorylation of MAP2K1 on S222. 2 / 2
2 |
bel
"To address a possible role of mutant C-RAF proteins in the constitutive phosphorylation of ERK1/2, kinase assays were done with Myc-tagged C-RAF proteins immunoprecipitated from transiently transfected Cos-7 cells. Strong constitutive kinase activity was shown for S427GC-RAF whereas I448VC-RAF did not significantly differ from wt C-RAF (Fig. 3A)."
bel
"Raf-1 activity, measured by the abundance of phosphorylated S217/221 MEK1 2, a direct target of Raf-1 (30) , was consistently elevated in Cdc37 overexpressing cells, whereas total MEK1 2 levels were unchanged."
RAF1 phosphorylated on T269 phosphorylates MAP2K1 on S222. 2 / 2
2 |
biopax:pid
No evidence text available
biopax:pid
No evidence text available
Phosphorylated RAF1 phosphorylates MAP2K1. 2 / 2
2 |
biopax:panther
No evidence text available
biopax:panther
No evidence text available
RAF1 phosphorylated on T269 and T268 phosphorylates MAP2K1 on S218. 2 / 2
2 |
biopax:pid
No evidence text available
biopax:pid
No evidence text available
RAF1 phosphorylated on T268 phosphorylates MAP2K1 on S218. 2 / 2
2 |
biopax:pid
No evidence text available
biopax:pid
No evidence text available
RAF1 phosphorylates MAP2K1 on T386. 2 / 2
2 |
hprd
No evidence text available
hprd
No evidence text available
RAF1 phosphorylated on T269 and S338 phosphorylates MAP2K1 on S218. 2 / 2
2 |
biopax:pid
No evidence text available
biopax:pid
No evidence text available
RAF1 phosphorylated on T269 phosphorylates MAP2K1 on S218. 2 / 2
2 |
biopax:pid
No evidence text available
biopax:pid
No evidence text available
RAF1 phosphorylates MAP2K1 on T286. 2 / 2
2 |
hprd
No evidence text available
hprd
No evidence text available
RAF1 phosphorylated on T269 and T268 phosphorylates MAP2K1 on S222. 2 / 2
2 |
biopax:pid
No evidence text available
biopax:pid
No evidence text available
RAF1 phosphorylated on S338 phosphorylates MAP2K1 on S218. 2 / 2
2 |
biopax:pid
No evidence text available
biopax:pid
No evidence text available
RAF1 phosphorylated on S621 and T268 phosphorylates MAP2K1 on T286. 1 / 1
1 |
biopax:pid
No evidence text available
RAF1 phosphorylates MAP2K1 phosphorylated on S298 on S222. 1 / 1
1 |
biopax:pid
No evidence text available
Kinase-active RAF1 phosphorylates MAP2K1. 1 / 1
1 |
bel
"acti-Fig. 3. PKCb in insulin signal-ing. Insulin-stimulated insulin receptor (IR) phosphorylates IRS1. IRS1 recruit various signaling molecules through SH2-phos-photyrosine interactions. IRS1-binding proteins containing an SH2 domain include Grb2, PI3K, SHP-2, and Nck. Insulin-induced ERK activation in L6 myocytes occurs largely through Raf-1 rather than Ras activation. In contrast, EGF-induced ERK acti-vation is dependent on Grb2/Sos-mediated Ras activation."
RAF1 phosphorylates MAP2K1 on T292. 1 / 1
1 |
hprd
No evidence text available
RAF1 phosphorylates MAP2K1 on S298. 1 / 1
| 1
rlimsp
"Phosphorylation of MEK1 on serine 298 does not appear to regulate the interaction between Raf-1 and MEK1, but rather the ability of Raf-1 to phosphorylate MEK1 with which it is complexed in vivo."
RAF1 phosphorylated on T269, S301, S471, S338, S296, and S289 phosphorylates MAP2K1 on S222. 1 / 1
1 |
biopax:pid
No evidence text available
RAF1 phosphorylates MAP2K1 phosphorylated on S298 on S218. 1 / 1
1 |
biopax:pid
No evidence text available
RAF1 phosphorylated on S621 and T268 phosphorylates MAP2K1 on T292. 1 / 1
1 |
biopax:pid
No evidence text available
RAF1 phosphorylated on S621 and T268 phosphorylates MAP2K1 on T386. 1 / 1
1 |
biopax:pid
No evidence text available
RAF1 phosphorylated on T269, S301, S471, S338, S296, and S289 phosphorylates MAP2K1 on S218. 1 / 1
1 |
biopax:pid
No evidence text available
RAF1 phosphorylated on an unknown residue, an unknown residue, an unknown residue, an unknown residue, an unknown residue, an unknown residue, an unknown residue, and an unknown residue phosphorylates MAP2K1. 1 / 1
1 |
biopax:panther
No evidence text available