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

The Vascular endothelial growth factor–Vascular endothelial growth factor receptor (VEGF–VEGFR) protein–protein interface is a critical regulatory node in the signaling pathway that governs angiogenesis, the formation of new blood vessels from pre-existing ones (UniProt P15692, P35968). This interface involves the binding of Vascular Endothelial Growth Factor (VEGF) ligands, primarily VEGF-A, to the extracellular immunoglobulin-like domains of Vascular Endothelial Growth Factor Receptors (VEGFR-1 and VEGFR-2). In healthy physiology, this interaction is essential for embryonic development and wound healing, but its dysregulation is a hallmark of pathological conditions such as tumor growth and neovascular eye diseases (PubMed: 12847517). Therapeutic strategies targeting this interface aim to disrupt the physical association between the ligand and receptor, thereby preventing receptor dimerization and the subsequent downstream signaling cascades that promote endothelial cell proliferation and survival. Monoclonal antibodies and decoy receptors are the primary classes of drugs that successfully target this interface to inhibit pathological angiogenesis (StatPearls: NBK507815). While highly effective in oncology and ophthalmology, disrupting this interface can lead to systemic side effects such as hypertension and impaired wound healing due to the role of VEGF in maintaining normal vascular function.

Other names

VEGF-VEGFR interactionVEGF-VEGFR binding siteVEGF-VEGFR signaling complexVEGF-VEGFR extracellular interface

Competitive inhibition of the physical association between VEGF ligands and the extracellular immunoglobulin-like domains of VEGFR receptors, which prevents receptor dimerization, autophosphorylation, and the activation of downstream pro-angiogenic signaling pathways (Ferrara et al., 2003, Nature Medicine).