Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. VEGFR2 gene encodes one of the two receptors of the VEGF. Two members of this receptor class, Flt-1 and Flk-1, have been shown to represent high affinity receptors for vascular endothelial growth factors (VEGFs). In response to VEGF binding, Flk-1 undergoes autophosphorylation in the kinase insert domain on Tyr 951 and Tyr 996 and in the tyrosine kinase catalytic domain on Tyr 1054 and Tyr 1059. Upon activation, Flk-1 recruits several adapter proteins, including Shc, Grb2, Nck and protein tyrosine phosphatases SHP-1 and SHP-2. The mediation of VEGF signaling by Flk-1 promotes proliferation, chemotaxis, prouting and angiogenesis.