VEGFA-VEGFR2 Signaling Pathway (Homo sapiens)

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95STAT3PROCK2PRKD2373795MAPK3T202Y204MAPK1T185Y1873262, 137MAPK1Y187T18594129, 243911151, 102, 16421417532, 90MAP2K3MAP2K6P2721MAPK9MAPK8Y185T183STAT3PMAPK3T183146MAPK3T202Y20414829, 49, 111, 183MAPK1Y18522PRKCZ80, 211PIK3R2ACACBNCF2MAPK12RAP1B133VEGFR2Y1059Y951Y996Y1054MeK1041Y1214Y11759992, 243197AP1complexSoluble andcleaved FLT1may sequesterVEGFA fromVEGFR2PKC delta/ZetadependentEpoxyeicosatrienoicacid regioisomersEC proliferation,migration,tube formationand angiogenesisCYCell motilityand tube formationEC Migration andTube Formation133, 154157FADDTCEB3FAF1FASBIN1BMXHDAC1TNFRSF10CHSPA1ASMARCA2226DOK1PGAB1PReceptorPROTEINLigandProtein translocation LEGENDMultiple colored edges are introduced to distinguish the connecting nodesPhosphorylated form with/without site & residueEndosomeNucleusMitochondrionCytoplasmPlasma membraneMTEndoplasmic reticulumCYPMNUERENVEGFR2Y1175Y951Y801Y1214Y1059Y1054127VEGFA252MAPK14P114, 225225F-actinreorganization20, 225225Stress fibreformationFocal adhesionassembly andcell migration225NCK1PFYNPPAK2P133STAT1PSTAT6P48, 134STAT1PSTAT6P134NUFRS2PCRKPPRKCI79797979133SRCY419Y530113130RAPGEF1148148RAP1AGTP148ITGAVITGB3Y773148BCAR1P127, 193PLCG1UbY783231SHC1193SHC219322, 133PTK2Y576Y861Y397S732Y407237IQGAP1PRAC1GTP100, 142197197Directed Cell migration73, 197, 202ITGB5ITGB1ITGAV16145, 161161161235SH2D2A174174207VascularpermeabilityNAADP152TPCN2Ca2+Ca2+Ca2+Ca2+Ca2+Ca2+152152H+H+H+ATPADP152152152Endolysosomalcalcium storeMAPKAPK2T334114, 234114114114PLAUPIP2IP3DAG333333CAPN2105Ca2+Ca2+Ca2+187MYL9S20T19237Endothelial cellcontraction athigh VEGFA levels237156ROCK1P156, 228RHOAGTP107, 118, 156, 228, 229100RHOCGTP146, 239Endothelial cellProliferationand migration146146MAP2K1S218S22292, 14614624, 113CBL242424ITPR133146PRKCBPRKCAS657223RAF1P102, 214, 223SPHK1PHRASGTP783361PRKD1S742S738S910946194, 157HDAC5S259S49894HDAC5S498S259PRKCDPRKCEPLA2G4AP10251, 102PGI2HSPB1S15S82S7855109NRP1247CAV1Y14130130130CDH5215PTPN11215CSK215215215204PTK2BY40224076, 80HSP90AA113913976, 13952MLLT4168168FHL220020059PLCB3S537S1105128128CDC42GTP128WASF1NCF1PPAK1P200195195PTPN968PTPRZ167676767NCLMYH9NCL13113113113150AKT1T308S47350FOXO1S256AKT1T308S47350, 86, 23050FOXO1S25627, 505050, 215, 224RELANFKBIA36P12612618, 57, 112, 126126PLA2G5RPS6KA5P474747145, 203PIK3R1P143145, 230NOS3S1179S11423155, 105, 145NO145LIMK1S323CFL155S3202020, 109VAV2Y172118118FLNB9191, 22091PFN1Y1297777G-actin bindingand actinpolymerization77At cellleadingedge11990, 138ATF2T69T71Promotes endothelial-leukocyte interactions909032Endothelialcell survival32, 218GRB2P113113139, 211PXNpY80, 93, 116170GJA1S279S262S282S255S368238ClathrinmediatedGap junctioninternalization111GJA1S262S255S279S282S368Stress fibreformation119PTPRJ192, 224192, 224224SHBP62626262144, 154144, 1541547676ROCK1P76RPS6KB1T4121TXNIPACP1S-glutathionylation1, 40TXN11, 40ONOO-1150, 125Cysteineoxidationof VEGFR2and SRCPTPN6181181GRB10P21013, 195PRKAA1T183ROSMitochondrial20213CytosolicROS132Angiogenesis13284, 13212, 38, 101cGMP38, 82Angiogenesis12, 38, 101CREB1P98CAMKK215, 84ACACAP84, 21315, 84PRKAA2202ARHGEF15167167RHOJ54GTP167167137SHC1S36137PDPK1S241243PIP2PIP3R1CTORMLST8MAPKAP1MTORS2448S24816969MTORRAPTORMLST8243243Non-phosphoform of SHC243NRDG1T345mTORC2mTORC1217117, 218GSK3BS9230166, 243243AKT1S1T266129129129RPS6S235S236129, 166203RAPTORMTORMLST8mTORC1166ER stress-independentVEGF-UPR machinerymediated pathwayEIF2AK3ERN1PATF6EIF2AS51166166166GeneexpressionATF4166166DNAJB9HERPUD1166AKT1S473166133119CAPN2187EZR105105105TRPC1ITPR1191KL121121Ca2+Ca2+Ca2+Ca2+Ca2+121191Calciumreleasefrom ERPIK3CA168TXNIPVEGFR21PLCG1Y783RAB5ACDH5S665CTNND1S252S268CTNNB1CTNNA1S453MAP2K1S222S218MAP2K2185185VEGFR2Y1214UbY117510Lysosomemediatedpartialproteosomaldegradation230 kDa160 kDaFBXW1110EEA144SLC8A1Ca2+