Vascular Endothelial Growth Factor Receptor-3 (VEGFR-3)

Vascular endothelial growth factor receptor-3 (VEGFR-3), also known as FLT4, is a receptor tyrosine kinase primarily involved in the regulation of lymphangiogenesis—the formation of lymphatic vessels. It is encoded by the FLT4 gene and plays essential roles in both development and maintenance of the lymphatic system. While VEGFR-1 and VEGFR-2 are more associated with blood vascular endothelium, VEGFR-3 is predominantly expressed on lymphatic endothelial cells but can also be found in certain blood microvascular beds under specific physiological or pathological conditions. The primary ligands for VEGFR-3 are Vascular endothelial growth factor-C (VEGF-C) and Vascular endothelial growth factor-D (VEGF-D). Upon ligand binding, homodimerization or heterodimerization occurs, leading to autophosphorylation of intracellular tyrosine residues, activating downstream pathways like AKT/PI3K and ERK/MAPK. Soluble splice variants act as decoy receptors, regulating local availability of active growth factors. Mutations or dysregulation contribute to various pathologies including congenital lymphedema syndromes. Overexpression/activity has been implicated in tumor metastasis via enhanced tumor-associated lymphangiogenesis.

Other names

FLT4

Tyrosine kinase inhibition; Decoy receptor function (soluble splice variants)