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

Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10705-9. doi: 10.1073/pnas.90.22.10705.

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.

MeSH terms

  • Alternative Splicing
  • Base Sequence
  • Cloning, Molecular
  • Cross-Linking Reagents
  • DNA Primers / chemistry
  • DNA, Complementary / genetics
  • Endothelial Growth Factors / antagonists & inhibitors*
  • Endothelium, Vascular / cytology
  • Gene Expression
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Lymphokines / antagonists & inhibitors*
  • Mitogens / antagonists & inhibitors
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • Receptor Protein-Tyrosine Kinases / chemistry
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptors, Growth Factor / chemistry
  • Receptors, Growth Factor / metabolism*
  • Receptors, Vascular Endothelial Growth Factor
  • Solubility
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Cross-Linking Reagents
  • DNA Primers
  • DNA, Complementary
  • Endothelial Growth Factors
  • Lymphokines
  • Mitogens
  • RNA, Messenger
  • Receptors, Growth Factor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor

Associated data

  • GENBANK/U01134