Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor.

TLDR

Vascular endothelial cell growth factor is a mitogen selective for vascular endothelial cells that promotes angiogenesis through distinct membrane‑spanning tyrosine kinase receptors. The authors cloned a cDNA encoding a soluble, truncated fms‑like tyrosine kinase receptor that, produced by alternative splicing, contains the six extracellular ligand‑binding domains but lacks the transmembrane and intracellular kinase regions. The soluble receptor is expressed in vascular endothelial cells, binds VEGF with high affinity, and potently inhibits its mitogenic activity, suggesting it could serve as a specific antagonist in vivo.

Abstract

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.