Vascular endothelial growth factor receptor 2 and Vascular endothelial growth factor receptor 3 (VEGFR-2 and VEGFR-3)

Vascular endothelial growth factor receptor 2 (VEGFR-2) and vascular endothelial growth factor receptor 3 (VEGFR-3) are membrane-bound receptor tyrosine kinases that mediate the effects of vascular endothelial growth factors. VEGFR-2, encoded by the KDR gene, is predominantly found on vascular endothelial cells and is the principal receptor for VEGF-A, playing a central role in angiogenesis and vascular permeability. VEGFR-3, encoded by the FLT4 gene, is expressed mainly in lymphatic endothelial cells and binds VEGF-C and VEGF-D, driving lymphangiogenesis, lymphatic vascular maintenance, and is critical in cancer metastasis. Both receptors possess extracellular domains containing seven Ig-like modules for ligand binding and dimerization, signal across the membrane, and initiate intracellular phosphorylation cascades that regulate cell growth, migration, differentiation, and survival. Dysregulation of VEGFR-2 and VEGFR-3 pathways is implicated in cancer, inflammation, cardiovascular changes, and lymphatic disorders[1][3][4][5][7]. Therapeutic targeting of VEGFR-2 and VEGFR-3 with monoclonal antibodies or small molecule kinase inhibitors forms the basis of many anti-angiogenic and anti-lymphangiogenic strategies in oncology and related diseases.

Other names

KDRFlk-1Flt4

Direct inhibition of ligand binding (e.g., antibodies to VEGF-A or VEGFR-2); Inhibition of receptor tyrosine kinase activity (small molecule TKIs competitively bind ATP site on intracellular kinase domain); Blockade of dimerization and downstream signaling; Suppression of endothelial or lymphatic cell proliferation, migration, and new vessel formation