The vascular endothelial growth factor (VEGF) family of soluble protein growth factors is master regulators of in vasculogenesis and angiogenesis during blood vessel development. In mammals, the VEGF family consists of 5 members, VEGFA, B, C, and D and placenta growth factor (PIGF). VEGFs act through three structurally related VEGF receptor tyrosine kinases, denoted VEGFR1 (FLT1), VEGFR2 (FLK1), and VEGFR3 (FLT4). Binding of VEGF to its cognate VEGF receptor in cis or trans (e.g., by binding HS proteoglycans [HSPGs] on adjacent cells induces receptor homo- or heterodimerization (Ref.1 and 2). VEGFA binds VEGFR1 and VEGFR2. VEGFR2 is expressed mainly in endothelial cells, whereas VEGFR1 is expressed in endothelial cells as well as hematopoietic stem cells and inflammatory cells, such as monocytes and macrophages, in which it regulates chemotaxis. The VEGFR1 tyrosine kinase receptor (TKR) mediates various biologic effects of VEGFA, B, and PlGF. Potential interacting partners of VEGFR1 include Phospholipase C-gamma, PI3K, SHP2, growth factor receptor-bound protein 2 (GRB2), and NCK. VEGF or PlGF binding to VEGFR1 induces phosphorylation and activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) (Ref.3 and 4). References:
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