VEGF signaling pathway - Homo sapiens (human)

Curator(s): Joe Strothman

There is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic angiogenesis. The binding of VEGF to VEGFR-2 leads to a cascade of different signaling pathways, resulting in the up-regulation of genes involved in mediating the proliferation and migration of endothelial cells and promoting their survival and vascular permeability. For example, the binding of VEGF to VEGFR-2 leads to dimerization of the receptor, followed by intracellular activation of the PLCgamma;PKC-Raf kinase-MEK-mitogen-activated protein kinase (MAPK) pathway and subsequent initiation of DNA synthesis and cell growth, whereas activation of the phosphatidylinositol 3' -kinase (PI3K)-Akt pathway leads to increased endothelial-cell survival. Activation of PI3K, FAK, and p38 MAPK is implicated in cell migration signaling.    
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VEGF signaling pathway - Homo sapiens (human) cluster_node21 !dag cluster_node22 !focal cluster_node23 !map cluster_node24 !aam cluster_node25 !apop node1 15 VEGF VEGF->node1 VEGF VEGFR2 VEGF->VEGFR2 VRAP VEGFR2->VRAP PLCgamma VEGFR2->PLCgamma Sck VEGFR2->Sck cell division cycle 42 (GTP binding protein,25kDa) CDC42 VEGFR2->CDC42 v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) SRC VEGFR2->SRC PI3K VEGFR2->PI3K Paxillin VEGFR2->Paxillin FAK VEGFR2->FAK IP3 PLCgamma->IP3 DAG PLCgamma->DAG p38 CDC42->p38 node2 2 SRC->node2 SRC SRC->PI3K node3 12 PI3K->node3 PI3K PIP3 PI3K->PIP3 node4 3 PIP3->node4 PIP3 Rac PIP3->Rac node16 Akt/PKB PIP3->node16 node5 Ca2+ IP3->node5 PKC node5->PKC cPLA2 node5->cPLA2 CALN node5->CALN eNOS node5->eNOS node6 2 p38->node6 p38 MAPKAPK p38->MAPKAPK +p node7 5 PKC->node7 PKC SPK PKC->SPK +p Ras SPK->Ras node8 1 Ras->node8 Ras v-raf-1 murine leukemia viral oncogene homolog 1 RAF1 Ras->RAF1 node9 2 node10 2 MEK MEK->node10 MEK ERK MEK->ERK +p node11 24 ERK->node11 ERK DNA 1 ERK->DNA 1 ERK->cPLA2 Proliferation DNA 1->Proliferation PGI2 cPLA2->PGI2 NFAT CALN->NFAT -p node12 2 NFAT->node12 NFAT DNA 2 NFAT->DNA 2 COX2 DNA 2->COX2 node13 8 COX2->node13 COX2 COX2->PGI2 Focal adhesion turnover Paxillin->Focal adhesion turnover Migration Focal adhesion turnover->Migration HSP27 MAPKAPK->HSP27 +p node14 3 HSP27->node14 HSP27 Actin reorganization HSP27->Actin reorganization Actin reorganization->Migration Rac->Migration Permeability Rac->Permeability node15 17 node17 3 eNOS->node17 eNOS NO eNOS->NO NO->Migration NO->Permeability node18 9 caspase 9,apoptosis-related cysteine peptidase CASP9 CASP9->node18 CASP9 node20 Survival (NFKB) CASP9->node20 node19 2 BCL2-associated agonist of cell death BAD BAD->node19 BAD BAD->node20 node16->node15 Akt/PKB node16->eNOS +p node16->CASP9 +p node16->BAD +p DAG->PKC FAK->Focal adhesion turnover RAF1->node9 RAF1 RAF1->MEK +p Calcium signaling pathway Focal adhesion MAPK Signaling Pathway Arachidonic acid metabolism Apoptosis print "