Neuropilin signalling in angiogenesis

VEGFs (vascular endothelial growth factors) are master regulators of vascular development and of blood and lymphatic vessel function during health and disease in adults. This family of five mammalian ligands acts through three RTKs (receptor tyrosine kinases). In addition, co-receptors such as NRPs (neuropilins) associate with the ligand–receptor signalling complex and modulate the output. Therapeutics to block several of the VEGF signalling components as well as NRP function have been developed with the aim of halting blood vessel formation, angiogenesis, in diseases that involve tissue growth and inflammation, such as cancer. The present review outlines the current understanding of NRPs in relation to blood and lymphatic vessel biology. Abbreviations: E, embryonic day; EC, endothelial cell; FGF, fibroblast growth factor; Gal1, galectin 1; GIPC, GAIP (Gα-interacting protein)-interacting protein C-terminus; HGF, hepatocyte growth factor; HSPG, heparan sulfate proteoglycan; JNK, c-Jun N-terminal kinase; NRP, neuropilin; p38MAPK, p38 mitogen-activated protein kinase; PDGF, platelet-derived growth factor; PDGFR, PDGF receptor; PlGF, placental growth factor; RTK, receptor tyrosine kinase; SAPK1, stress-activated protein kinase 1; TC, tumour cell; TGFβ, transforming growth factor β; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor; VSMC, vascular smooth muscle cell