Vascular endothelial growth factor receptor 1, Vascular endothelial growth factor receptor 2, and Vascular endothelial growth factor receptor 3 (VEGFR1, VEGFR2, VEGFR3)

Vascular endothelial growth factor receptors 1/2/3 are a family of closely related cell-surface receptor tyrosine kinases that mediate cellular responses to members of the vascular endothelial growth factor family. Each is composed structurally of an extracellular region with seven immunoglobulin-like domains responsible for ligand binding; a single transmembrane helix; and an intracellular split tyrosine kinase domain responsible for signal transduction upon activation by dimerization and autophosphorylation. Functional distinctions: VEGFR‑1 primarily modulates angiogenic signaling by acting as a decoy or negative regulator but also participates directly in monocyte/macrophage migration. VEGFR‑2 is considered the principal mediator driving angiogenic responses such as proliferation and migration in vascular endothelium. VEGFR‑3 is mainly involved in lymphangiogenesis through its interaction with specific ligands like VEGF-C/D. These receptors play essential roles not only during embryonic development but also in adult physiology—regulating blood vessel formation—and are implicated pathologically when dysregulated during cancer progression via tumor neovascularization. As such they represent validated therapeutic targets across multiple cancers and other diseases characterized by abnormal vessel formation.

Other names

Fms-related tyrosine kinase 1 (FLT1) [VEGFR-1]Kinase insert domain receptor (KDR) [VEGFR-2]Fetal liver kinase 1 (FLK1) [VEGFR-2]Fms-related tyrosine kinase 4 (FLT4) [VEGFR-3]

Drugs targeting these receptors typically act as inhibitors—either monoclonal antibodies or small molecules—that block ligand binding or inhibit the intracellular tyrosine kinase activity. This prevents downstream signaling required for angiogenesis and tumor vascularization.