Vascular endothelial growth factor receptor signaling complex (VEGF signaling complex)

The Vascular Endothelial Growth Factor (VEGF) induced signaling complex is a multi-protein assembly that serves as the primary regulator of angiogenesis and vascular permeability. This complex is initiated when VEGF ligands, such as VEGF-A, bind to the extracellular domains of their cognate receptor tyrosine kinases, primarily Vascular Endothelial Growth Factor Receptor 2 (VEGFR2/KDR) [UniProt P35968]. This binding event induces receptor dimerization and autophosphorylation of intracellular tyrosine residues, which then serve as docking sites for downstream signaling proteins like Phospholipase C-gamma (PLC-gamma), PI3K, and Shc [PubMed: 21354607]. These pathways collectively promote endothelial cell survival, proliferation, and migration, which are essential for the formation of new blood vessels [Nature Reviews Molecular Cell Biology, 2006]. In many cancers, the overproduction of VEGF by tumor cells leads to constitutive activation of this complex, driving pathological angiogenesis that supports tumor growth and metastasis [Nature Reviews Drug Discovery, 2016]. Therapeutic strategies targeting this complex include monoclonal antibodies like bevacizumab that sequester the VEGF ligand, and small-molecule tyrosine kinase inhibitors like sunitinib that block the intracellular signaling of the receptors [FDA: Avastin Label; FDA: Sutent Label]. While effective, these therapies are often associated with physiological effects such as hypertension and proteinuria, due to the role of VEGF signaling in maintaining normal vascular homeostasis [Nature Reviews Clinical Oncology, 2009].

Other names

VEGF/VEGFR axisVEGF signaling pathwayVEGF-VEGFR complexVascular endothelial growth factor signaling axis

Inhibition of VEGF ligand binding, inhibition of VEGFR tyrosine kinase activity, and neutralization of circulating VEGF ligands.