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Characterization of the VEGF binding site on the Flt-1 receptor.

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Herley M.T., Yu Y., Whitney R.G., Sato J.D.

The angiogenic growth factor VEGF binds to the receptor tyrosine kinases Flt-1 and KDR/Flk-1. Immunoglobulin (Ig)-like loop-2 of Flt-1 is involved in binding VEGF, but the contribution of other Flt-1 Ig-loops to VEGF binding remains unclear. We tested the ability of membrane-bound chimeras between the extracellular domain of Flt-1 and the cell adhesion molecule embigin to bind VEGF. VEGF bound as well to receptors containing Flt-1 loops 1-2 or 2-3 as it did to the entire Flt-1 extracellular domain. Chimeras containing only loop-2 of Flt-1 bound VEGF with 22-fold lower affinity. We conclude that high-affinity VEGF binding requires Ig-like loop-2 plus either loop-1 or loop-3. In addition, Flt-1 amino acid residues Arg-224 and Asp-231 were not essential for high-affinity binding of VEGF to membrane-bound Flt-1.

Biochem. Biophys. Res. Commun. 262:731-738(1999) [PubMed] [Europe PMC]