Figure 1: VEGF receptor binding. The five mammalian vascular endothelial growth factors (VEGF-A-D) bind to the receptor tyrosine kinases, VEGF receptor (VEGFR1-3 and co-receptors HSPG, NRP-1 and NRP-2). VEGFR-binding leads to the formation of homodimers and/or heterodimers. Proteolytic cleavage enables VEGF-C and -D to bind VEGFR-2 forming a homodimer. The binding and activation of VEGFR-2 lead to downstream signaling of the PI3 K, MAPK, and Ras pathways which promote cell survival, proliferation, differentiation, migration, and angiogenesis.