◀ Back to MAPK1
MAPK1 — RAF1
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
MAPK1
→
RAF1
(increases, RAF1 Activity, MAPK1 Activity)
Evidence: activation of ERK depended on EGFR, Src tyrosine kinase and calcium calmodulin in PC12 cells (31), while requiring ras/Raf-1/MEK activation in human neutrophils (58).
-
OpenBEL Selventa BEL large corpus:
MAPK1
→
RAF1
(increases, RAF1 Activity, MAPK1 Activity)
Illario et al., J Biol Chem 2003*
Evidence: inhibition of CaMKII activity by specific inhibitors inhibited Erk-1/2 phosphorylation. Whereas CaMK inhibition affected neither integrin-stimulated Akt phosphorylation nor p21Ras or Mek-1 activity, it was necessary for Raf-1 activity...Active CaMKII phosphorylated Raf-1 in vitro.
-
OpenBEL Selventa BEL large corpus:
MAPK1
→
RAF1
(directlyIncreases, MAPK1 Activity)
Wang et al., Cell 1996*
Evidence: Plasma membrane-targeted Raf-1 did not protect from apoptosis and resulted in phosphorylation of ERK-1 and ERK-2
-
OpenBEL Selventa BEL large corpus:
MAPK1
→
RAF1
(decreases, RAF1 Activity)
Evidence: This inhibitory phosphorylation on Raf reduces the activity of MAPK pathway (Zimmermann and Moelling, 1999).
-
BioCarta role of ß-arrestins in the activation and targeting of map kinases:
Ligand/GPCR(+)/Arrestin/RAF1/MEK1/MEK2/ERK1/ERK2 complex (CCL4_EDN1__AGT_CCL11_CXCL12_F2_compound:CAS66575-29-9_compound:CAS745-65-3-ARRB1-RAF1-MAP2K1-MAP2K2-MAPK3-MAPK1)
→
MEK2 (MAP2K2)
(modification, collaborate)
-
BioCarta role of ß-arrestins in the activation and targeting of map kinases:
Ligand/GPCR(+)/Arrestin/RAF1/MEK1/MEK2/ERK1/ERK2 complex (CCL4_EDN1__AGT_CCL11_CXCL12_F2_compound:CAS66575-29-9_compound:CAS745-65-3-ARRB1-RAF1-MAP2K1-MAP2K2-MAPK3-MAPK1)
→
RAF1
(modification, collaborate)
-
BioCarta role of ß-arrestins in the activation and targeting of map kinases:
Ligand/GPCR(+)/Arrestin/RAF1/MEK1/MEK2/ERK1/ERK2 complex (CCL4_EDN1__AGT_CCL11_CXCL12_F2_compound:CAS66575-29-9_compound:CAS745-65-3-ARRB1-RAF1-MAP2K1-MAP2K2-MAPK3-MAPK1)
→
ERK2 (MAPK1)
(modification, collaborate)
-
BioCarta role of ß-arrestins in the activation and targeting of map kinases:
Ligand/GPCR(+)/Arrestin/RAF1/MEK1/MEK2/ERK1/ERK2 complex (CCL4_EDN1__AGT_CCL11_CXCL12_F2_compound:CAS66575-29-9_compound:CAS745-65-3-ARRB1-RAF1-MAP2K1-MAP2K2-MAPK3-MAPK1)
→
Ligand/GPCR(+)/Arrestin complex (CCL4_EDN1__AGT_CCL11_CXCL12_F2_compound:CAS66575-29-9_compound:CAS745-65-3-ARRB1)
(modification, collaborate)
-
BioCarta role of ß-arrestins in the activation and targeting of map kinases:
Ligand/GPCR(+)/Arrestin/RAF1/MEK1/MEK2/ERK1/ERK2 complex (CCL4_EDN1__AGT_CCL11_CXCL12_F2_compound:CAS66575-29-9_compound:CAS745-65-3-ARRB1-RAF1-MAP2K1-MAP2K2-MAPK3-MAPK1)
→
MEK1 (MAP2K1)
(modification, collaborate)
-
BioCarta role of ß-arrestins in the activation and targeting of map kinases:
Ligand/GPCR(+)/Arrestin/RAF1/MEK1/MEK2/ERK1/ERK2 complex (CCL4_EDN1__AGT_CCL11_CXCL12_F2_compound:CAS66575-29-9_compound:CAS745-65-3-ARRB1-RAF1-MAP2K1-MAP2K2-MAPK3-MAPK1)
→
ERK1 (MAPK3)
(modification, collaborate)
-
BioCarta role of ß-arrestins in the activation and targeting of map kinases:
RAF1
→
ERK2 (MAPK1)
(modification, collaborate)
-
BioCarta role of ß-arrestins in the activation and targeting of map kinases:
Ligand/GPCR(+)/Arrestin/RAF1/MEK1/MEK2/ERK1/ERK2 complex (CCL4_EDN1__AGT_CCL11_CXCL12_F2_compound:CAS66575-29-9_compound:CAS745-65-3-ARRB1-RAF1-MAP2K1-MAP2K2-MAPK3-MAPK1)
→
dynamin gtpase (DNM1)
(translocation, collaborate)
-
BioCarta role of ß-arrestins in the activation and targeting of map kinases:
Ligand/GPCR(+)/Arrestin/RAF1/MEK1/MEK2/ERK1/ERK2 complex (CCL4_EDN1__AGT_CCL11_CXCL12_F2_compound:CAS66575-29-9_compound:CAS745-65-3-ARRB1-RAF1-MAP2K1-MAP2K2-MAPK3-MAPK1)
→
Ligand/GPCR(+)/Arrestin/RAF1/MEK1/MEK2/ERK1/ERK2(cy) complex (CCL4_EDN1__AGT_CCL11_CXCL12_F2_compound:CAS66575-29-9_compound:CAS745-65-3-ARRB1-RAF1-MAP2K1-MAP2K2-MAPK3-MAPK1)
(translocation, collaborate)
-
BioCarta role of ß-arrestins in the activation and targeting of map kinases:
dynamin gtpase (DNM1)
→
Ligand/GPCR(+)/Arrestin/RAF1/MEK1/MEK2/ERK1/ERK2(cy) complex (CCL4_EDN1__AGT_CCL11_CXCL12_F2_compound:CAS66575-29-9_compound:CAS745-65-3-ARRB1-RAF1-MAP2K1-MAP2K2-MAPK3-MAPK1)
(translocation, activates)
-
KEGG Hepatitis C:
ARAF/BRAF/RAF1
→
MAPK1/MAPK3
(protein-protein, activation)
-
NCI Pathway Database PDGFR-beta signaling pathway:
Erk1-2-active (MAPK3/MAPK1)
→
RAF1/14-3-3 complex (RAF1-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB)
(modification, activates)
Brummer et al., Oncogene 2003, Dougherty et al., Mol Cell 2005, McKay et al., Proc Natl Acad Sci U S A 2009, Ritt et al., Mol Cell Biol 2010
Evidence: assay, physical interaction
-
NCI Pathway Database PDGFR-beta signaling pathway:
Erk1-2-active (MAPK3/MAPK1)
→
RAF1/BRAF/14-3-3/14-3-3 complex (RAF1-BRAF-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB)
(modification, activates)
Brummer et al., Oncogene 2003, Dougherty et al., Mol Cell 2005, McKay et al., Proc Natl Acad Sci U S A 2009, Ritt et al., Mol Cell Biol 2010
Evidence: assay, physical interaction
-
NCI Pathway Database ErbB1 downstream signaling:
Erk1-2-active (MAPK3/MAPK1)
→
RAF1/BRAF complex (RAF1-BRAF)
(modification, activates)
Rushworth et al., Mol Cell Biol 2006, Wu et al., J Biol Chem 1996*
Evidence: assay
-
NCI Pathway Database ErbB1 downstream signaling:
Erk1-2-active (MAPK3/MAPK1)
→
RAF1 (RAF1)
(modification, activates)
Balan et al., Mol Biol Cell 2006*
Evidence: assay, physical interaction
-
NCI Pathway Database CDC42 signaling events:
Erk1-2 (MAPK3/MAPK1)
→
RAF1-BRAF (RAF1/BRAF)
(modification, collaborate)
Koh et al., J Cell Sci 2008, Koh et al., J Cell Sci 2009
Evidence: mutant phenotype
-
NCI Pathway Database CDC42 signaling events:
RAF1-BRAF (RAF1/BRAF)
→
Erk1-2-active (MAPK3/MAPK1)
(modification, activates)
Koh et al., J Cell Sci 2008, Koh et al., J Cell Sci 2009
Evidence: mutant phenotype
-
Reactome Reaction:
RAF1
→
MAPK1
(reaction)
García et al., J Cell Biochem 2008*
-
WikiPathways Focal Adhesion-PI3K-Akt-mTOR-signaling pathway:
RAF1
→
MAPK1
(activation)
-
WikiPathways Angiopoietin Like Protein 8 Regulatory Pathway:
RAF1
→
MAP2K1/MAP3K7/MAPK14/MAPK1/MAP2K2/MAP3K2/MAP3K6/MAPK8/MAP4K1/MAP3K11/MAP4K3/MAPK10/MAP2K7/MAP3K4/MAP3K1/MAP3K12/MAPK4/MAPK11/MAP4K5/MAPK6/MAP4K4/MAPK3/MAP3K14/MAPK12/MAP2K5/MAP2K4/MAPK13/MAP3K5/MAPK9/MAPK7/MAP3K3/MAP3K9/MAP3K8/MAP2K6/MAP3K13/MAP4K2/MAP2K3/MAP3K10/MINK1
(activation)
-
WikiPathways Insulin Signaling:
RAC1/GRB2/SOS1/RAC2/RRAD/GRB14/SOS2/RAF1/HRAS/GRB10
→
MINK1/MAP4K4/MAP3K2/MAPK12/MAP3K5/MAPK10/MAP3K3/MAP4K1/MAPK3/MAP2K7/MAPK13/MAP3K1/MAP4K3/MAP2K6/MAP3K8/MAP3K12/MAP2K4/MAPK7/MAPK14/MAP3K11/MAP3K7/MAPK11/MAPK9/MAPK6/MAP3K13/MAP2K3/MAPK4/MAP4K2/MAP2K5/MAP3K10/MAPK1/MAP2K1/MAP3K6/MAP3K4/MAP3K9/MAP4K5/MAP2K2/MAPK8/MAP3K14
(activation)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Bind_translation Interaction:
RAF1
—
MAPK1
(experimental interaction detection)
Dougherty et al., Mol Cell 2005
-
IRef Biogrid Interaction:
RAF1
—
MAPK1
(direct interaction, enzymatic study)
Dougherty et al., Mol Cell 2005
-
IRef Biogrid Interaction:
RAF1
—
MAPK1
(direct interaction, enzymatic study)
Zhu et al., Mol Biol Cell 2005
-
IRef Biogrid Interaction:
RAF1
—
MAPK1
(physical association, affinity chromatography technology)
Blaukat et al., Mol Cell Biol 2000*
-
IRef Biogrid Interaction:
RAF1
—
MAPK1
(physical association, affinity chromatography technology)
Lin et al., Mol Cell Biol Res Commun 2000*
-
IRef Hprd Interaction:
RAF1
—
MAPK1
(in vivo)
Dougherty et al., Mol Cell 2005
-
IRef Hprd Interaction:
RAF1
—
MAPK1
(in vitro)
Dougherty et al., Mol Cell 2005
-
IRef Hprd Interaction:
Complex of RAF1-MAPK1-PEBP1-RAF1-MAPK1-PEBP1-MAPK1-PEBP1-RAF1
(in vivo)
Park et al., FEBS Lett 2006*
-
IRef Hprd Interaction:
Complex of 51 proteins
(in vivo)
Luttrell et al., Proc Natl Acad Sci U S A 2001
-
IRef Hprd Interaction:
Complex of ARRB2-MAPK1-RAF1-RAF1-ARRB2-RAF1-MAPK1-MAPK1-ARRB2
(in vivo)
Shenoy et al., J Biol Chem 2007*
-
IRef Intact Interaction:
Complex of RAF1-MAPK1-MAPK3-MDM2
(association, anti tag coimmunoprecipitation)
Beaulieu et al., Cell 2008*
Text-mined interactions from Literome
Shibayama et al., Blood 1999
:
8-Br-cAMP, Dibutyryl-cAMP,
Ras-Raf-1 pathway inhibitors, and PD98059, a
MAPK kinase
inhibitor , suppressed proliferation and phosphorylation of MAPK detected by Western blotting with anti-phospho-MAPK antibody, but not adhesion of any type of H-Ras transfected Baf3 cells, whereas U-73122, a phospholipase C (PLC) inhibitor, suppressed adhesion of these cells completely
Kalmes et al., FEBS Lett 1999
:
We conclude that activation of
Raf-1 by SB203580 is not
mediated by an inhibition of p38
MAPK , is Ras independent, and is uncoupled from MEK/ERK signaling
Majewski et al., Cancer Res 1999
:
Inhibition of plasma membrane
Raf-1 dependent
mitogen activated protein kinase activity had no effect on the enhanced survival of cells expressing Akt
Samadder et al., Cancer Res 1999
(Breast Neoplasms) :
We have previously shown that inhibition of MCF-7 cell proliferation by 1-O-octadecyl-2-O-methyl-glycerophosphocholine ( ET-18-OCH3 ) is linked to a drug induced decrease in membrane
Raf-1 levels and the subsequent
inhibition of
mitogen activated protein ( MAP ) kinase activation in response to growth factor stimulation
Teng et al., J Biol Chem 1999
:
We report here that Ras ( C118S ) functions indistinguishably from wild type Ras in activating and maintaining the mSOS1- and
Raf-1 dependent
mitogen activated protein kinase cascade necessary for neuronal differentiation
Lee et al., Proc Natl Acad Sci U S A 2000
:
Finally, activation of
MAPK by p53 was
inhibited by expression of dominant negative Ras ( N17Ras ) and
Raf1 mutants, indicating that MAPK activation by p53 is mediated at a level upstream of Ras
Banihashemi et al., Mol Endocrinol 2002
:
These results indicate that the dopamine-D2S receptor couples to distinct G ( i/o ) proteins, depending on the pathway addressed, and suggest a novel Galpha(i)3/Galpha ( o ) -dependent inhibition of
MAPK mediated by
c-Raf and B-Raf dependent inhibition of MAPK/ERK kinase
Kurokawa et al., Clin Cancer Res 2003
(Breast Neoplasms...) :
Aberrant signaling by receptors of the erbB network up-regulates a number of signaling pathways, which include phospholipase C-gamma1,
Ras-Raf-mitogen activated protein/extracellular signal regulated kinase
kinase-mitogen activated protein kinase , phosphatidylinositol 3'-kinase and its target, the serine/threonine kinase Akt, stress activated protein kinases, signal transducers and activators of transcription, and c-Jun-NH ( 2 ) -terminal kinase ( JNK )
Ostrovsky et al., J Biol Chem 2003
(MAP Kinase Signaling System) :
Specific
activation of
MAPK by expression of an active
Raf1-estrogen receptor chimera protein reduced significantly the number of myoblasts undergoing programmed cell death in the differentiation medium
Kyriakis et al., Nature 1992
:
These results indicate that
c-Raf-1 is an immediate upstream
activator of
MAPK-K in vivo
Yu et al., Oncogene 2004
(Leukemia) :
These events were accompanied by the caspase independent downregulation of
Raf-1 , inactivation of MEK1/2, ERK, Akt, p70S6K, dephosphorylation of GSK-3, and
activation of c-Jun-N-terminal kinase (JNK) and p38
MAPK
Trakul et al., J Biol Chem 2005
(MAP Kinase Signaling System) :
Here, we show that RKIP
inhibits MAPK by regulating
Raf-1 activation ; specifically, RKIP acts subsequent to Raf-1 membrane recruitment, prevents association of Raf-1 and p21 activated kinase (PAK), and blocks phosphorylation of the Raf-1 kinase domain by PAK and Src family kinases ... Because
c-Raf-1 and B-Raf are both
required for maximal
MAPK stimulation by epidermal growth factor in neuronal and epithelial cell lines, we determined whether RKIP significantly affects MAPK signaling
Tartaglia et al., Molecular syndromology 2010
:
SHP2 ( encoded by PTPN11 ), SOS1, BRAF,
RAF1 and MEK1 positively
contribute to
RAS-MAPK signaling, and possess complex autoinhibitory mechanisms that are impaired by mutations
Siddhanti et al., Endocrinology 1995
:
We found that PMA stimulated DNA synthesis was associated with increments in tyrosine phosphorylation of p44mapk ( ERK1 ) and
p42mapk ( ERK2 ) and
activation of
Raf-1 , MKK, and MAPK in these cells ... FSK treatment of osteoblasts, which raised intracellular cAMP levels and inhibited DNA synthesis, blocked PKC stimulated tyrosine phosphorylation of p44mapk ( ERK1 ) and
p42mapk ( ERK2 ) as well as
inhibited PKC stimulated MAPK and
Raf-1 activities
Samuels et al., Mol Cell Biol 1994
:
Addition of beta-estradiol to quiescent C2 cells led to rapid, sustained activation of delta
Raf-1 : ER and MEK but only two- to threefold
activation of
p42 mitogen activating protein ( MAP ) kinase activity
Izquierdo et al., J Exp Med 1994
:
The
role of
Raf-1 in the regulation of
extracellular signal regulated kinase 2 by the T cell antigen receptor
Kharbanda et al., J Biol Chem 1994
(Leukemia, Myeloid) :
Since
Raf-1 can
activate the
mitogen activated protein ( MAP ) kinases , we also studied the relationship between MAP kinase activation and monocytic differentiation
Kyriakis et al., J Biol Chem 1993
:
Although PDGF/insulin stimulated c-Raf-1 Ser/Thr phosphorylation may be necessary to sustain the active state, a
role for
mitogen activated protein kinase/extracellular signal regulated kinase-2 phosphorylation in the initiation of
c-Raf-1 activation is unlikely ... Although PDGF/insulin stimulated c-Raf-1 Ser/Thr phosphorylation may be necessary to sustain the active state, a
role for mitogen activated protein
kinase/extracellular signal regulated kinase-2 phosphorylation in the initiation of
c-Raf-1 activation is unlikely
Whitehurst et al., J Immunol 1996
:
Active
Raf-1 phosphorylates and
activates the
mitogen activated protein ( MAP ) kinase/extracellular signal regulated kinase kinase 1 ( MEK1 ), which in turn phosphorylates and activates the MAP kinases/extracellular signal regulated kinases, ERK1 and ERK2
Lazarini et al., J Neurochem 1996
:
IRL1620 induced
MAPK activation
involved the adapter proteins Shc and Grb2 and the serine/threonine kinase
Raf-1
Radziwill et al., Biochem Biophys Res Commun 1996
:
This lipid induced
MAPK activation is
blocked by a
Raf-1 derived peptide comprising Ser259
Pumiglia et al., Proc Natl Acad Sci U S A 1997
:
Activation of delta
RAF-1 : ER
resulted in a prolonged increase in
MAPK activity and growth arrest of these cells, with concomitant induction of p21Cip1/WAF1 and inhibition of CDK2 activity
Mazure et al., Blood 1997
(Cell Transformation, Neoplastic...) :
In this report, we show Ras transformed cells do not use the downstream effectors
c-Raf-1 or mitogen
activated protein kinases (
MAPK ) in signaling VEGF induction by hypoxia as overexpression of kinase-defective alleles of these genes does not inhibit VEGF induction under low oxygen conditions
Lu et al., J Neurochem 1998
:
Raf-1 dependent
activation of mitogen activated protein kinase (
MAPK ) is the key in the chronic norepinephrine neuromodulatory actions of Ang II and is associated with the translocation of MAPK into the nucleus
Hoshino et al., J Biol Chem 1998
(Leukemia, Myeloid) :
Thus, LTD4 has at least two distinct signaling pathways in THP-1 cells, a PTX-insensitive
mitogen activated protein kinase activation through protein kinase Calpha and
Raf-1 and a PTX-sensitive chemotactic response
Greene et al., Eur J Neurosci 1998
:
The two FGFs induce an equivalent level of tyrosine phosphorylation of
mitogen activated protein kinase ( MAPK ) and
c-raf activation
Howe et al., J Biol Chem 1998
:
We show that integrin mediated activation of
Raf-1 , an upstream
regulator of
mitogen activated protein kinase , occurs in two phases