VEGFR-3/FLT-4

VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk 1) and VEGFR-3 (FLT-4) belong to the class III subfamily of receptor tyrosine kinases (RTKs) . All three receptors contain seven immunoglobulin-like repeats in their extracellular domains and kinase insert domains in their intracellular regions. The expression of VEGFR-1 to -3 is almost exclusively restricted to hematopoietic precursor cells, vascular and lymphatic endothelial cells and to the monocyte/macrophage lineage. These receptors play essential roles in vasculogenesis, hematopoiesis, angiogenesis and lymphangiogenesis. The VEGFR-3 cDNA encodes a 1298 amino acid (aa) residue precursor protein with a 24 aa residue signal peptide. Mature VEGFR-3 is composed of a 751 aa residue extracellular domain, a 22 aa residue transmembrane domain and a 482 aa residue cytoplasmic domain. Both VEGF-C and VEGF-D have been shown to bind and activate VEGF R3 (Flt-4) . The Flt-4 gene is widely expressed in the early embryo but becomes restricted to the lymphatic endothelial a latter stage of development. It is important for lymphangiogenesis.