VEGF R2 (KDR/Flk-1), VEGF R1 (Flt-1) and VEGF R3 (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 VEGF R1, 2, and 3 is almost exclusively restricted to the endothelial cells. These receptors are likely to play essential roles in vasculogenesis and angiogenesis.
VEGF R3 cDNA encodes a 1298 amino acid (aa) residue precursor protein with a 24 aa residue signal peptide. Mature VEGF R3 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). VEGF R3 is widely expressed in the early embryo but becomes restricted to lymphatic endothelia at later stages of development. It is likely that VEGF R3 may be important for lymph angiogenesis.
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