VEGF Receptor and Ligands

The receptors for vascular epithelial growth factor (VEGF) and related ligands include VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4), neuropilin-1, and neuropilin-2. The interaction of VEGFR with either neuropilin-1 (NRP-1) or heparin sulfate proteoglycan may facilitate the presentation and binding of VEGF to its receptor. These receptors have multiple immunoglobulin G-like extracellular domains and intracellular tyrosine kinase activity. There are several splice variants of VEGF, including VEGF 121, 145, 165, 189, and 206, with VEGF165 being the predominant form. Other members of the VEGF family have been cloned including VEGF-B, -C, and -D and placental growth factor (PlGF). VEGF binds to VEGFR-1 and -2 and is involved in triggering angiogenesis. PlGF is localized to the placenta and binds only to VEGFR-1. VEGF-B also binds only to VEGFR-1 and appears to be involved in coronary vascularization and growth. VEGF-C and VEGF-D activate VEGFR-2 and -3 but not VEGF-1. VEGF-C is implicated in lymphangiogenesis. The function of VEGF-D is unknown.

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References:

Yancopoulos, G.D., et al., Vascular-specific growth factors and blood vessel formation. Nature, 407, 242-248 (2000).

Shima, D.T., and Mailhos, C., Vascular developmental biology: getting nervous. Curr. Opin. Gen. Dev., 10, 536-542 (2000).

Robinson, C.J., and Stringer, S.E., The splice variants of vascular endothelial growth factor (VEGF) and their receptors. J. Cell Sci., 114, 853-865 (2001).