Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor.
Vascular endothelial cell growth factor, a mitogen selective for vascular endothelial cells in vitro that promotes angiogenesis in vivo, functions through distinct membrane-spanning tyrosine kinase receptors. The cDNA encoding a soluble truncated form of one such receptor, fms-like tyrosine kinase receptor, has been cloned from a human vascular endothelial cell library. The mRNA coding region distinctive to this cDNA has been confirmed to be present in vascular endothelial cells. Soluble fms-like tyrosine kinase receptor mRNA, generated by alternative splicing of the same pre-mRNA used to produce the full-length membrane-spanning receptor, encodes the six N-terminal immunoglobulin-like extracellular ligand-binding domains but does not encode the last such domain, transmembrane-spanning region, and intracellular tyrosine kinase domains. The recombinant soluble human receptor binds vascular endothelial cell growth factor with high affinity and inhibits its mitogenic activity for vascular endothelial cells; thus this soluble receptor could act as an efficient specific antagonist of vascular endothelial cell growth factor in vivo.
Kendall
R L
RL
Department of Biochemistry, Merck Research Laboratories, Rahway, NJ 07065.
Thomas
K A
KA
D017398:Alternative Splicing; D001483:Base Sequence; D003001:Cloning, Molecular; D003432:Cross-Linking Reagents; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors*; D004730:Endothelium, Vascular / Q000166:cytology; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008222:Lymphokines / Q000037:antagonists & inhibitors*; D008934:Mitogens / Q000037:antagonists & inhibitors; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000737:chemistry / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor; D012995:Solubility; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D003432:Cross-Linking Reagents; D017931:DNA Primers; D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D008222:Lymphokines; D008934:Mitogens; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor