VEGFR-1/Flt-1 (D4), soluble

Recombinant Human soluble Vascular Endothelial Growth Factor Receptor-1 domain D1-4 (sVEGFR-1 (D4) ) is produced as a non-chimeric protein in a monomeric form. The soluble receptor protein contains only the first 4 extracellular domains, which contain all the information necessary for binding of VEGF. The receptor monomers have a mass of approximately 55 kDa containing 457 amino acid residues. Endothelial cells express three different vascular endothelial growth factor (VEGF) receptors, belonging to the family of receptor tyrosine kinases (RTKs) . They are named VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), VEGFR-3 (Flt-4) . Their expression is almost exclusively restricted to endothelial cells, but VEGFR-1 can also be found on monocytes, dendritic cells and on trophoblast cells. The flt-1 gene was first described in 1990. The receptor contains seven immunoglobulin-like extracellular domains, a single transmembrane region and an intracellular split tyrosine kinase domain. Compared to VEGFR-2 the Flt-1 receptor has a higher affinity for VEGF but a weaker signaling activity. VEGFR-1 thus leads not to proliferation of endothelial cells, but mediates signals for differentiation. Interestingly a naturally occuring soluble variant of VEGFR-1 (sVEGFR-1) was found in HUVEC supernatants in 1996, which is generated by alternative splicing of the flt-1 mRNA. The biological functions of sVEGFR-1 still are not clear, but it seems to be an endogenous regulator of angiogenesis, binding VEGF with the same affinity as the full-length receptor.