Vascular endothelial growth factor receptor 1 (VEGFR-1) and Vascular endothelial growth factor receptor 2 (VEGFR-2) (VEGFR1/VEGFR2)

Vascular endothelial growth factor receptor 1 ("VEGFR-1", FLT1) and vascular endothelial growth factor receptor 2 ("VEGFR-2", KDR) are **receptor tyrosine kinases** located on vascular endothelial cells that mediate responses to VEGF family cytokines. VEGFR-2 is the principal mediator of **angiogenesis** and **vascular permeability**, promoting endothelial cell proliferation, migration, and new vessel formation in health and in pathologies such as cancer and retinopathies. VEGFR-1, despite binding VEGF-A with higher affinity, is a relatively **kinase-impaired** receptor thought to act as a *decoy* or regulator, limiting VEGFR-2 signaling under physiological conditions[1][2][3][4]. Both receptors share homologous architecture: an extracellular domain with seven immunoglobulin-like repeats, a single transmembrane helix, and a cytoplasmic tyrosine kinase domain split by a kinase insert. Activation of these receptors initiates cascades involving cell survival, proliferation, and migration pathways, critical for both normal vascular homeostasis and pathologic conditions, especially tumor angiogenesis. Numerous targeted therapies have been developed to inhibit this pathway at the levels of ligand, receptor, or kinase activity. Note on correctness: "VEGFR1/VEGFR2" refers to two separate but closely related therapeutic targets. For structuring, information should ideally be split into "Vascular endothelial growth factor receptor 1" (VEGFR-1) and "Vascular endothelial growth factor receptor 2" (VEGFR-2)[1][2][3][4].

Other names

FLT1fetal liver kinase 1Fms-like tyrosine kinase 1KDRkinase insert domain receptorFlk-1

Inhibition of ligand binding (e.g., antibodies against VEGF-A reduce activation of both VEGFR-1 and VEGFR-2); Inhibition of tyrosine kinase activity (small molecule inhibitors block ATP binding and phosphorylation); Ligand sequestration (VEGFR-1 can act as a decoy, limiting VEGFR-2 activation)