IDENTIFICATION OF A NATURAL SOLUBLE FORM OF THE VASCULAR ENDOTHELIAL GROWTH-FACTOR RECEPTOR, FLT-1, AND ITS HETERODIMERIZATION WITH KDR

A soluble form of the vascular endothelial growth factor (VEGF) recept or FLT-1 was identified in conditioned culture medium of human umbilic al vein endothelial cells. The endogenous soluble FLT-1 (sFLT-1) recep tor is chromatographically and immunologically similar to recombinant human sFLT-1 and binds [I-125]VEGF with a comparable high affinity. Hu man sFLT-1 is shown to form a VEGF-stabilized complex with the extrace llular domain of KDR in vitro, suggesting that not only full-length re ceptors are capable of forming ligand-induced heterodimeric complexes but also sFLT-1 can form a dominant negative complex with the mitogeni cally competent full-length KDR receptor. (C) 1996 Academic Press, Inc .