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) receptor FLT-1 was identified in conditioned culture medium of human umbilical vein endothelial cells. The endogenous soluble FLT-1 (sFLT-1) receptor is chromatographically and immunologically similar to recombinant human sFLT-1 and binds [125I]VEGF with a comparable high affinity. Human sFLT-1 is shown to form a VEGF-stabilized complex with the extracellular domain of KDR in vitro, suggesting that not only full-length receptors are capable of forming ligand-induced heterodimeric complexes but also sFLT-1 can form a dominant negative complex with the mitogenically competent full-length KDR receptor.
Kendall
R L
RL
Department of Pharmacology, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Wang
G
G
Thomas
K A
KA
D000595:Amino Acid Sequence; D001704:Biopolymers; D002478:Cells, Cultured; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1
D001704:Biopolymers; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1