Several crucial phosphorylated sites Tyr801, Try951, Try1175, and Try1214 in the VEGFR-2 intracellular domains mediate several key signaling processes including PLCγ-PKC, TSAd-Src-PI3K-Akt, SHB-FAK-paxillin, SHB-PI3K-Akt, and NCK-p38-MAPKAPK2/3 pathways. Finally the VEGF-activated VEGFR-2 stimulates and mediates variety of signaling transduction, biological responses, and pathological processes in angiogenesis. The VEGF binding to the IgD2 and IgD3 of VEGFR-2 induces the dimerization of the receptor, subsequently the activation and trans-autophosphorylation of the tyrosine kinase, and then the initiation of the intracellular signaling cascades. This series of signaling cascade pathways are precisely mediated by VEGF/VEGFR-2 system. Angiogenesis is an important mechanism in many physiological and pathological processes, and is involved in endothelial cell proliferation, migration, and survival, then leads to further tubulogenesis, and finally promotes formation of vessels. The vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) play crucial roles in vasculogenesis and angiogenesis. 3Department of Medicine/Hematology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States.2Regina Elena National Cancer Institute, Rome, Italy.1College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China.Xinrong Wang 1*, Alfredo Maria Bove 2, Giuseppe Simone 2 and Binyun Ma 3*
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