Vascular endothelial growth factor–Vascular endothelial growth factor receptor protein–protein interaction interface (VEGF–VEGFR PPI interface)

The Vascular endothelial growth factor (VEGF)–Vascular endothelial growth factor receptor (VEGFR) protein–protein interaction interface is a critical regulatory site for angiogenesis and vascular permeability (UniProt P15692; UniProt P35968). This interface involves the binding of dimeric VEGF ligands (primarily VEGF-A) to the extracellular immunoglobulin-like domains 2 and 3 of VEGFR-1 and VEGFR-2 (PMID: 11084330). Upon binding, the receptors undergo dimerization and subsequent intracellular tyrosine kinase activation, which triggers signaling pathways such as MAPK/ERK and PI3K/Akt that promote endothelial cell survival, proliferation, and migration (PMID: 12359721). In many pathological conditions, particularly solid tumors and exudative ocular diseases, the overactivation of this interface leads to excessive and disorganized blood vessel growth (PMID: 15549097). Therapeutic strategies targeting this interface include monoclonal antibodies that sequester the ligand (e.g., bevacizumab) or block the receptor (e.g., ramucirumab), as well as decoy receptors (e.g., aflibercept) that mimic the binding site to trap VEGF (FDA: Avastin Label; FDA: Cyramza Label). These interventions are standard of care in oncology and ophthalmology but are associated with systemic side effects like hypertension and impaired wound healing due to the inhibition of physiological vascular maintenance (PMID: 17938230).

Other names

VEGF-VEGFR binding siteVEGF-VEGFR complex interfaceVEGF-VEGFR signaling interface

Inhibition of ligand-receptor binding by neutralizing the ligand or blocking the receptor's extracellular binding site, thereby preventing receptor dimerization and downstream signaling.