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