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

  • Kendall R
  • Thomas K
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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.

Author-supplied keywords

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

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Authors

  • R L Kendall

  • K A Thomas

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