All three VEGF receptors belong to the class III subfamily of receptor tyrosine kinases （RTKs） characterised by the seven immunoglobulin-like loops in the extracellular domain. 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. They play key roles in vasculogenesis， hematopoiesis， angiogenesis and lymphangiogenesis. The FLT-4 cDNA encodes a 1298 amino acid （aa） residue precursor protein with a 23 aa residue signal peptide. Mature VEGFR-3/FLT-4 is composed of a 751 aa residue extracellular domain， a 22 aa transmembrane domain and a 482 aa residue cytoplasmic domain. Both VEGF family members VEGF-C and VEGF-D have been shown to bind and activate VEGFR-3/FLT-4. The Flt-4 gene is widely expressed in the early embryo but becomes restricted to the lymphatic endothelial a latter stages of development. It is important for lymphangiogenesis.
