VEGFA-VEGFR2 Signaling Pathway (Homo sapiens)

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94STAT3PROCK2PRKD2363694MAPK3Y204T202MAPK1Y187T1853161, 136MAPK1Y187T18593128, 242911050, 101, 16321317431, 89MAP2K3MAP2K6P2620MAPK9MAPK8Y185T183STAT3PMAPK3T183145MAPK3Y204T20214728, 48, 110, 182MAPK1Y18521PRKCZ79, 210PIK3R2ACACBNCF2MAPK12RAP1B132VEGFR2Y1054Y1059Y1175Y996Y951Y1214MeK10419891, 242196AP1complexPKC delta/ZetadependentSoluble andcleaved FLT1may sequesterVEGFA fromVEGFR2Epoxyeicosatrienoicacid regioisomersEC proliferation,migration,tube formationand angiogenesisCYCell motilityand tube formationEC Migration andTube Formation132, 153156FADDTCEB3FAF1FASBIN1BMXHDAC1TNFRSF10CHSPA1ASMARCA2225DOK1PGAB1PReceptorPROTEINLigandProtein translocation LEGENDMultiple colored edges are introduced to distinguish the connecting nodesPhosphorylated form with/without site & residueEndosomeNucleusMitochondrionCytoplasmPlasma membraneMTEndoplasmic reticulumCYPMNUERENVEGFR2Y1059Y801Y1054Y951Y1175Y1214126VEGFA251MAPK14P113, 224224F-actinreorganization19, 224224Stress fibreformationFocal adhesionassembly andcell migration224NCK1PFYNPPAK2P132STAT1PSTAT6P47, 133STAT1PSTAT6P133NUFRS2PCRKPPRKCI78787878132SRCY419Y530112129RAPGEF1147147RAP1AGTP147ITGAVITGB3Y773147BCAR1P126, 192PLCG1Y783Ub230SHC1192SHC219221, 132PTK2Y397Y576Y407S732Y861236IQGAP1PRAC1GTP99, 141196196Directed Cell migration72, 196, 201ITGB5ITGB1ITGAV16044, 160160160234SH2D2A173173206VascularpermeabilityNAADP151TPCN2Ca2+Ca2+Ca2+Ca2+Ca2+Ca2+151151H+H+H+ATPADP151151151Endolysosomalcalcium storeMAPKAPK2T334113, 233113113113PLAUPIP2IP3DAG323232CAPN2104Ca2+Ca2+Ca2+186MYL9T19S20236Endothelial cellcontraction athigh VEGFA levels236155ROCK1P155, 227RHOAGTP106, 117, 155, 227, 22899RHOCGTP145, 238Endothelial cellProliferationand migration145145MAP2K1S222S21891, 14514523, 112CBL232323ITPR132145PRKCBPRKCAS657222RAF1P101, 213, 222SPHK1PHRASGTP773260PRKD1S742S910S738936093, 156HDAC5S259S49893HDAC5S259S498PRKCDPRKCEPLA2G4AP10150, 101PGI2HSPB154S15S82S78108NRP1246CAV1Y14129129129CDH5214PTPN11214CSK214214214203PTK2BY40223975, 79HSP90AA113813875, 13851MLLT4167167FHL219919958PLCB3S1105S537127127CDC42GTP127WASF1NCF1PPAK1P199194194PTPN967PTPRZ166666666NCLMYH9NCL13013013013049AKT1T308S47349FOXO1S256AKT1T308S47349, 85, 22949FOXO1S25626, 494949, 214, 223RELANFKBIA35P12512517, 56, 111, 125125PLA2G5RPS6KA5P464646144, 202PIK3R1P142144, 229NOS3S114S117923054, 104, 144NO144LIMK1S323CFL1S354191919, 108VAV2Y172117117FLNB9090, 21990PFN1Y1297676G-actin bindingand actinpolymerization76At cellleadingedge11889, 137ATF2T71T69Promotes endothelial-leukocyte interactions898931Endothelialcell survival31, 217GRB2P112112138, 210PXNpY79, 92, 115169GJA1S368S262S279S282S255237ClathrinmediatedGap junctioninternalization110GJA1S262S282S368S279S255Stress fibreformation118PTPRJ191, 223191, 223223SHBP61616161143, 153143, 1531537575ROCK1P75RPS6KB1T4121TXNIPACP1S-glutathionylation1, 39TXN11, 39ONOO-1149, 124Cysteineoxidationof VEGFR2and SRCPTPN6180180GRB10P20913, 194PRKAA1T183ROSMitochondrial20113CytosolicROS131Angiogenesis13183, 13112, 37, 100cGMP37, 81Angiogenesis12, 37, 100CREB1P97CAMKK214, 83ACACAP83, 21214, 83PRKAA2201ARHGEF15166166RHOJGTP53166166136SHC1S36136PDPK1S241242PIP2PIP3R1CTORMLST8MAPKAP1MTORS2481S24486868MTORRAPTORMLST8242242Non-phosphoform of SHC242NRDG1T345mTORC2mTORC1216116, 217GSK3BS9229165, 242242AKT1S1T266128128128RPS6S236S235128, 165202RAPTORMTORMLST8mTORC1165ER stress-independentVEGF-UPR machinerymediated pathwayEIF2AK3ERN1PATF6EIF2AS51165165165GeneexpressionATF4165165DNAJB9HERPUD1165AKT1S473165132118CAPN2186EZR104104104TRPC1ITPR1190KL120120Ca2+Ca2+Ca2+Ca2+Ca2+120190Calciumreleasefrom ERPIK3CA167TXNIPVEGFR21PLCG1Y783RAB5ACDH5S665CTNND1S268S252CTNNB1CTNNA1S453MAP2K1S218S222MAP2K2184184VEGFR2Y1214UbY117510Lysosomemediatedpartialproteosomaldegradation230 kDa160 kDaFBXW1110EEA144SLC8A1Ca2+Ca2+Ca2+