VEGFVEGFR2

VEGFVEGFR2 refers to the signaling axis formed by vascular endothelial growth factor (VEGF) ligands and the VEGF receptor-2 (VEGFR-2), a receptor tyrosine kinase encoded by the KDR gene in humans and known as Flk-1 in mice. VEGFR-2 is a type I transmembrane protein with an extracellular region containing seven immunoglobulin-like domains that bind VEGF ligands, a single transmembrane helix, and an intracellular tyrosine kinase domain that becomes activated upon ligand binding.

VEGF-A is the main ligand for VEGFR-2; other VEGF family members and processing steps modulate affinity. Binding induces receptor dimerization and autophosphorylation on tyrosine residues, creating docking sites for signaling molecules and activating pathways such as PLCγ, PI3K-Akt, Ras-MAPK, and p38. This promotes endothelial cell proliferation, migration, survival, and increases vascular permeability.

Physiological and pathological roles include essential involvement in vasculogenesis and angiogenesis during development; in adults, the axis regulates wound healing and collateral vessel formation. Abnormal activation contributes to pathological angiogenesis in cancer and ocular diseases such as neovascular eye disorders.

Regulation and clinical relevance: VEGF expression is induced by hypoxia via HIF-1α. Soluble decoy receptors and receptor tyrosine kinase inhibitors can dampen signaling. Anti-VEGF therapies (for example, bevacizumab) and VEGFR2 inhibitors are used in cancer treatment and in diseases like wet age-related macular degeneration, reflecting the axis’s importance as a therapeutic target.