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

Vascular endothelial growth factor receptor 1 (VEGFR1, encoded by FLT1) and vascular endothelial growth factor receptor 2 (VEGFR2, encoded by KDR) are structurally related receptor tyrosine kinases predominantly expressed on vascular endothelial cells. Both receptors share a similar architecture: an extracellular region containing seven immunoglobulin-like domains, a transmembrane segment, and an intracellular split kinase domain. VEGFR2 is the principal mediator of VEGF-induced angiogenic signaling, driving endothelial proliferation, migration, and permeability by binding VEGF-A, VEGF-C, and VEGF-D. VEGFR1, which also binds VEGF-A (with higher affinity than VEGFR2), VEGF-B, and placental growth factor (PlGF), functions primarily as a negative regulator or decoy, sequestering VEGF to restrain excessive VEGFR2 activation, and has relatively weak kinase activity. Both receptors play essential roles in physiological and pathological angiogenesis and are validated therapeutic targets in cancer and other angiogenesis-driven diseases.

Other names

VEGFR1: Fms-like tyrosine kinase 1 (FLT1)VEGFR2: Kinase insert domain-containing receptor (KDR), Fetal liver kinase 1 (Flk-1)

Inhibition of ligand binding (antibodies, soluble receptors); Inhibition of tyrosine kinase activity (small molecule inhibitors); Downregulation of VEGF-VEGFR2 signaling pathway (prevents angiogenesis, tumor growth)