VEGFA-VEGFR2 Signaling Pathway (Homo sapiens)

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27STAT3PROCK2PRKD2535327, 102MAPK3Y204T202MAPK1Y187T18558126, 129MAPK1Y187T185155214, 2712301236, 22, 2452544758, 234MAP2K3MAP2K6P24939MAPK9MAPK8Y185T183STAT3PMAPK3T183228MAPK3Y204T20218645, 123, 146, 173MAPK1Y185127PRKCZ128, 238PIK3R2ACACBNCF2MAPK12RAP1B33VEGFR2Y1175Y996Y1214Y1054Y951Y1059MeK104189201188, 214149AP1complexSoluble andcleaved FLT1may sequesterVEGFA fromVEGFR2PKC delta/ZetadependentEpoxyeicosatrienoicacid regioisomersEC proliferation,migration,tube formationand angiogenesisCYCell motilityand tube formationEC Migration andTube FormationABCF233, 11418FADDTCEB3FAF1FASBIN1BMXHDAC1TNFRSF10CHSPA1ASMARCA257DOK1PGAB1PReceptorPROTEINLigandProtein translocation LEGENDMultiple colored edges are introduced to distinguish the connecting nodesPhosphorylated form with/without site & residueEndosomeNucleusMitochondrionCytoplasmPlasma membraneMTEndoplasmic reticulumCYPMNUERENVEGFR2Y1214Y1175Y951Y801Y1059Y105430VEGFA259MAPK14P117, 190117F-actinreorganization117, 162117Stress fibreformationFocal adhesionassembly andcell migration117NCK1PFYNPPAK2P33STAT1PSTAT6P105, 137STAT1PSTAT6P137NUFRS2PCRKPPRKCI1515151533SRCY530Y4192087RAPGEF1186186RAP1AGTP186ITGAVITGB3Y773186BCAR1P17630, 187PLCG1UbY78316SHC1187, 213SHC218733, 127PTK2Y397S732Y407Y576Y861168IQGAP1PRAC1133, 207GTP149149Directed Cell migration135, 149, 215ITGB5ITGB1ITGAV1717, 811717222SH2D2A175175223VascularpermeabilityNAADP65TPCN2Ca2+Ca2+Ca2+Ca2+Ca2+Ca2+6565H+H+H+ATPADP656565Endolysosomalcalcium storeMAPKAPK2T33469, 190190190190PLAUPIP2IP3DAG274274274CAPN2138Ca2+Ca2+Ca2+166MYL2S20T19168Endothelial cellcontraction athigh VEGFA levels16851ROCK1P51, 75RHOAGTP35, 50, 51, 75, 119...207RHOCGTP3, 228Endothelial cellProliferationand migration228228MAP2K1S218S222188, 22822820, 163CBL163163163ITPR1274228PRKCBPRKCAS65790RAF1P6, 90, 254SPHK1PHRAS19GTP27410PRKD1S742S738S9101551018, 155HDAC5S498S259155HDAC5S259S498PRKCDPRKCEPLA2G4AP66, 22PGI2HSPB1S7892S15S82150NRP1130, 201CAV1Y14878787CDH5106PTPN11106CSK10610610674PTK2BY402132128, 185HSP90AA1464646, 185267MLLT4210210FHL214014038PLCB3S1105S5372626CDC42GTP26WASF1NCF1PPAK1P140152152PTPN988PTPRZ160606060NCLMYH9NCL122122122122109AKT1S473T308109FOXO1S256AKT1S473T30823, 109, 202109FOXO1S256109, 249109106, 109, 250RELANFKBIAP268919163, 91, 165, 26191PLA2G5RPS6KA5P767676136, 154PIK3R1P73154, 202NOS3S1179S1141692, 138, 154NO154LIMK1S323CFL1S392162162150, 162VAV2Y1725050, 100FLNB9898, 20498PFN1Y12944G-actin bindingand actinpolymerization4At cellleadingedge1142, 234ATF2T71T69Promotes endothelial-leukocyte interactions23423458Endothelialcell survival58, 134GRB2P2020, 10046, 238PXNpY9, 128, 20336GJA1S368S255S262S279S282184ClathrinmediatedGap junctioninternalization123GJA1S282S255S279S368S262Stress fibreformation11PTPRJ250, 251250, 251250SHBP129129129129114, 235114, 235114185185ROCK1P185RPS6KB1T41256TXNIPACP1S-glutathionylation56, 131TXN5656, 131ONOO-5656109, 273Cysteineoxidationof VEGFR2and SRCPTPN6216216GRB10P5531, 152PRKAA1T183ROSMitochondrial21531CytosolicROS79Angiogenesis7979, 8549, 121, 246cGMP121, 164Angiogenesis49, 121, 246CREB1P68CAMKK285, 217ACACAP85, 20085, 217PRKAA2215ARHGEF156464RHOJGTP2576464126SHC1S36126, 213PDPK1S241214PIP2PIP3R1CTORMLST8MAPKAP1MTORS2481S2448199199MTORRAPTORMLST8214214214NRDG1T345mTORC2mTORC1