Kinase Subfamily VEGFR

Kinase Classification: Group TK: Family PVR: Subfamily VEGFR

Evolution

VEGFR is the founding subfamily of PVR, present in a wide range of metazoans. A triplication of the VEGFR subfamily in chordates gave rise to the PDGFR and Kit subfamilies. Three members are found in all vertebrates: VEGFR1 (FLT1), VEGFR2 (KDR) and VEGFR3 (FLT4). A fourth member, tentatively called FLT5, is found in fish.

Domain Structure

The extracellular region consists of 7 Immunoglobulin repeats, flanked by a signal peptide and a transmembrane region, while the intracellular region encodes a kinase domain and several other important short functional motifs. Secreted soluble versions of all three receptors are formed by alternative splicing and modulate VEGFR signaling.

Function

These receptors are involved in angiogenesis and vasculogenesis, with KDR being the best characterized. Several kinase inhibitors have been developed to block the development of new blood supplies for tumors by inhibiting VEGFR (Sutent, Nexavar, Votrient) or ligand binding (Avastin, Lucentis).