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MAP2K2 — RAF1

Pathways - manually collected, often from reviews:

• OpenBEL Selventa BEL large corpus: MAP2K2 → Complex of MAP2K1-RAF1 (increases, MAP2K1/RAF1 Activity)
  Evidence: Summary: Raf-1 is a MAP kinase kinase kinase (MAP3K) which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated Raf-1 can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2 which in turn phosphorylate to activate the serine/threonine specific protein kinases ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cel...
• OpenBEL Selventa BEL large corpus: MAP2K2 → RAF1 (directlyIncreases, MAP2K2 Activity)
  Evidence: 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.
• OpenBEL Selventa BEL large corpus: MAP2K2 → RAF1 (increases, RAF1 Activity)
  Evidence: Summary: Raf-1 is a MAP kinase kinase kinase (MAP3K) which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated Raf-1 can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2 which in turn phosphorylate to activate the serine/threonine specific protein kinases ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cel...
• 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: MEK2 (MAP2K2) → 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) → 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 Vascular smooth muscle contraction: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG VEGF signaling pathway: RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Gap junction: RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Natural killer cell mediated cytotoxicity: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG T cell receptor signaling pathway: RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG B cell receptor signaling pathway: RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Fc epsilon RI signaling pathway: RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Long-term potentiation: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Neurotrophin signaling pathway: BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Long-term depression: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Regulation of actin cytoskeleton: ARAF/BRAF/MOS/RAF1 → MAP2K1/MAP2K2 (protein-protein, phosphorylation)
• KEGG Insulin signaling pathway: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG GnRH signaling pathway: RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG MAPK signaling pathway: RAF1 → MAP2K2 (protein-protein, phosphorylation)
• KEGG Melanogenesis: RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Influenza A: RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Pathways in cancer: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Renal cell carcinoma: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Endometrial cancer: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Glioma: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Glioma: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Prostate cancer: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Melanoma: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Bladder cancer: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Chronic myeloid leukemia: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Acute myeloid leukemia: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG Non-small cell lung cancer: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• KEGG ErbB signaling pathway: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2 (protein-protein, activation)
• NCI Pathway Database ErbB2/ErbB3 signaling events: MEK1-2 (MAP2K1/MAP2K2) → RAF1 (RAF1) (modification, collaborate) Monje et al., J Biol Chem 2008
  Evidence: assay
• NCI Pathway Database PDGFR-beta signaling pathway: KSR/14-3-3 /MEK1-2 complex (KSR1-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB-MAP2K1_MAP2K2) → RAF1/BRAF/14-3-3/14-3-3 complex (RAF1-BRAF) (modification, collaborate)
  Ory et al., Curr Biol 2003, McKay et al., Proc Natl Acad Sci U S A 2009, Rajakulendran et al., Nature 2009, Ritt et al., Mol Cell Biol 2010, Reuter et al., J Biol Chem 1995
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database Nongenotropic Androgen signaling: MEK1-2 (MAP2K1/MAP2K2) → RAF1 (RAF1) (modification, collaborate) Unni et al., Cancer Res 2004
  Evidence: assay
• NCI Pathway Database mTOR signaling pathway: RAF1-BRAF (RAF1/BRAF) → MEK1-2-active (MAP2K1/MAP2K2) (modification, activates)
  Roux et al., Proc Natl Acad Sci U S A 2004
• NCI Pathway Database mTOR signaling pathway: RAF1-BRAF (RAF1/BRAF) → MEK1-2 (MAP2K1/MAP2K2) (modification, activates) Roux et al., Proc Natl Acad Sci U S A 2004
• NCI Pathway Database Signaling events mediated by VEGFR1 and VEGFR2: MEK1-2 (MAP2K1/MAP2K2) → RAF1 (RAF1) (modification, collaborate) Takahashi et al., Oncogene 1999*
  Evidence: genetic interaction
• NCI Pathway Database PDGFR-beta signaling pathway: MEK1-2 (MAP2K1/MAP2K2) → RAF1 (RAF1) (modification, collaborate) Beeser et al., J Biol Chem 2005*
  Evidence: mutant phenotype
• NCI Pathway Database PDGFR-beta signaling pathway: KSR/14-3-3 /MEK1-2 complex (KSR1-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB-MAP2K1_MAP2K2) → RAF1/14-3-3 complex (RAF1-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB) (modification, collaborate)
  McKay et al., Proc Natl Acad Sci U S A 2009
  Evidence: mutant phenotype, assay
• NCI Pathway Database ErbB1 downstream signaling: RAF1 (RAF1) → MEK2 (MAP2K2) (modification, activates) Catalanotti et al., Nature structural & molecular biology 2009, McKay et al., Proc Natl Acad Sci U S A 2009
  Evidence: assay, physical interaction
• NCI Pathway Database Endothelins: MEK1-2 (MAP2K1/MAP2K2) → RAF1 (RAF1) (modification, collaborate)
• NCI Pathway Database CXCR3-mediated signaling events: MEK1-2 (MAP2K1/MAP2K2) → RAF1 (RAF1) (modification, collaborate) Bonacchi et al., J Biol Chem 2001, Smit et al., Blood 2003
  Evidence: assay
• NCI Pathway Database GMCSF-mediated signaling events: MEK1-2 (MAP2K1/MAP2K2) → RAF1 (RAF1) (modification, collaborate) Guthridge et al., Blood 2004, Lanfrancone et al., Oncogene 1995, Sato et al., EMBO J 1993
• NCI Pathway Database PDGFR-beta signaling pathway: MEK1-2 (MAP2K1/MAP2K2) → RAF1 (RAF1) (modification, collaborate)
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): MEK1-2 (MAP2K1/MAP2K2) → RAF1 (RAF1) (modification, collaborate) Paumelle et al., Oncogene 2002, Errede et al., Mol Reprod Dev 1995*
  Evidence: assay
• Reactome Reaction: RAF1 → MAP2K2 (reaction)
• Reactome Reaction: RAF1 → MAP2K2 (indirect_complex)
• WikiPathways ESC Pluripotency Pathways: BRAF/RAF1/ARAF → MAP2K1/MAP2K3/SEPP1/MAP2K5/MAP2K6/MAP2K2 (activation)
  
• WikiPathways Focal Adhesion: ARAF/BRAF/RAF1 → SEPP1/MAP2K5/MAP2K6/MAP2K2/MAP2K3/MAP2K1 (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)
  
• WikiPathways 4-hydroxytamoxifen, Dexamethasone, and Retinoic Acids Regulation of p27 Expression: RAF1 → Complex of MAP2K2-MAP2K1 (activation)
• WikiPathways MAPK Cascade: RAF1/ARAF/BRAF → MAP2K1/MAP2K2 (activation)
• WikiPathways MicroRNAs in cardiomyocyte hypertrophy: RAF1 → MAP2K1/MAP2K2 (activation)
• WikiPathways Pathways Affected in Adenoid Cystic Carcinoma: RAF1 → MAP2K2 (activation)
• WikiPathways Serotonin Receptor 2 and ELK-SRF/GATA4 signaling: RAF1 → MAP2K2 (mim-necessary-stimulation) Suttles et al., J Biol Chem 1999*, Deszo et al., J Biol Chem 2001*, Alessi et al., J Biol Chem 1995*
• WikiPathways Signaling Pathways in Glioblastoma: ARAF/BRAF/RAF1 → MAP2K1/MAP2K2/MAP2K3/MAP2K4/MAP2K5/MAP2K6/MAP2K7 (mim-stimulation)
  
• WikiPathways Signaling of Hepatocyte Growth Factor Receptor: RAF1 → MAP2K2/MAP2K1 (activation)
• WikiPathways T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection: RAF1 → Complex of MAP2K2-MAP2K1 (activation)
• WikiPathways Cardiac Hypertrophic Response: RAF1 → MAP2K2/MAP2K1 (activation)
• WikiPathways Common Pathways Underlying Drug Addiction: RAF1/ARAF/ARAF → MAP2K1/MAP2K2 (activation)

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

• IRef Bind Interaction: RAF1 — MAP2K2 Matheny et al., Nature 2004
• IRef Bind_translation Interaction: RAF1 — MAP2K2 (coimmunoprecipitation) Matheny et al., Nature 2004
• IRef Biogrid Interaction: RAF1 — MAP2K2 (physical association, affinity chromatography technology) Xia et al., Genes Dev 1998*
• IRef Biogrid Interaction: RAF1 — MAP2K2 (direct interaction, two hybrid) Wang et al., Molecular systems biology 2011
• MIPS CORUM KSR1-RAF1-MEK complex: KSR1-RAF1-MEK complex complex (KSR1-RAF1-MAP2K1-MAP2K2) Chen et al., J Biol Chem 2008
• IRef Corum Interaction: Complex of RAF1-MAP2K2-MAP2K1-KSR1 (association, anti tag coimmunoprecipitation) Chen et al., J Biol Chem 2008
• IRef Hprd Interaction: RAF1 — MAP2K2 (in vitro) Alessi et al., EMBO J 1994*, Wu et al., Mol Cell Biol 1993*, Tanimura et al., Oncogene 1998*, Xia et al., Genes Dev 1998*
• IRef Hprd Interaction: RAF1 — MAP2K2 (in vivo) Alessi et al., EMBO J 1994*, Wu et al., Mol Cell Biol 1993*, Tanimura et al., Oncogene 1998*, Xia et al., Genes Dev 1998*
• IRef Intact Interaction: RAF1 — MAP2K2 (physical association, two hybrid) Yin et al., Biochim Biophys Acta 2002*
• IRef Intact Interaction: RAF1 — MAP2K2 (physical association, two hybrid) Wang et al., Molecular systems biology 2011
• IRef Intact Interaction: Complex of 143 proteins (association, anti tag coimmunoprecipitation)
• IRef Ophid Interaction: RAF1 — MAP2K2 (aggregation, interologs mapping) Brown et al., Bioinformatics 2005
• STRING interaction: MAP2K2 — RAF1 (interaction, mapped from bind reactome)
• STRING interaction: RAF1 — MAP2K2 (interaction, mapped from grid bind kegg_pathways)

Text-mined interactions from Literome

Zouki et al., FASEB J 2001 (MAP Kinase Signaling System) : ONOO- stimulation of Erk activity was accompanied by activation of Ras, Raf-1 and MEK ( mitogen activated protein kinase kinase ), and was sensitive to the MEK inhibitor PD 98059
Pal et al., Int J Oncol 2005 (Prostatic Neoplasms) : Raf-1 , a protein serine-threonine kinase, plays a critical role in mitogen activated protein kinase kinase ( MKK/MEK ) - mitogen activated protein kinase ( extracellular signal regulated kinase ) ( MAPK/ERK ) pathways
Ziogas et al., J Biol Chem 1998 : In addition, mitotic activation of Raf-1 does not lead to stimulation of the mitogen activated protein kinase kinase ( MAPKK or MEK ) and the extracellular signal regulated protein kinase ( ERK )