An essential heparin-binding domain in the fibroblast growth factor receptor kinase

Science. 1993 Mar 26;259(5103):1918-21. doi: 10.1126/science.8456318.

Abstract

Heparin or heparin-like heparan sulfate proteoglycans are obligatory for activity of the heparin-binding fibroblast growth factor (FGF) family. Heparin interacts independently of FGF ligand with a specific sequence (K18K) in one of the immunoglobulin-like loops in the extracellular domain of the FGF receptor tyrosine kinase transmembrane glycoprotein. A synthetic peptide corresponding to K18K inhibited heparin and heparin-dependent FGF binding to the receptor. K18K and an antibody to K18K were antagonists of FGF-stimulated cell growth. Point mutations of lysine residues in the K18K sequence abrogated both heparin- and ligand-binding activities of the receptor kinase. The results indicate that the FGF receptor is a ternary complex of heparan sulfate proteoglycan, tyrosine kinase transmembrane glycoprotein, and ligand.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal
  • Binding Sites
  • Fibroblast Growth Factors / metabolism
  • Heparan Sulfate Proteoglycans
  • Heparin / metabolism*
  • Heparitin Sulfate / metabolism
  • Humans
  • Immunohistochemistry
  • Lysine / metabolism
  • Metalloendopeptidases / metabolism
  • Molecular Sequence Data
  • Mutagenesis
  • Peptide Fragments / isolation & purification
  • Peptide Fragments / metabolism
  • Protein-Tyrosine Kinases / chemistry
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Proteoglycans / metabolism
  • Receptors, Fibroblast Growth Factor / chemistry
  • Receptors, Fibroblast Growth Factor / genetics
  • Receptors, Fibroblast Growth Factor / metabolism*
  • Recombinant Proteins / metabolism
  • Sodium Chloride / pharmacology
  • Trypsin / metabolism

Substances

  • Antibodies, Monoclonal
  • Heparan Sulfate Proteoglycans
  • Peptide Fragments
  • Proteoglycans
  • Receptors, Fibroblast Growth Factor
  • Recombinant Proteins
  • Sodium Chloride
  • Fibroblast Growth Factors
  • Heparin
  • Heparitin Sulfate
  • Protein-Tyrosine Kinases
  • Trypsin
  • Metalloendopeptidases
  • peptidyl-Lys metalloendopeptidase
  • Lysine