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An essential heparin-binding domain in the fibroblast growth factor receptor kinase.
- Source :
-
Science (New York, N.Y.) [Science] 1993 Mar 26; Vol. 259 (5103), pp. 1918-21. - Publication Year :
- 1993
-
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.
- Subjects :
- Amino Acid Sequence
Antibodies, Monoclonal
Binding Sites
Fibroblast Growth Factors metabolism
Heparan Sulfate Proteoglycans
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
Proteoglycans metabolism
Receptors, Fibroblast Growth Factor chemistry
Receptors, Fibroblast Growth Factor genetics
Recombinant Proteins metabolism
Sodium Chloride pharmacology
Trypsin metabolism
Heparin metabolism
Protein-Tyrosine Kinases metabolism
Receptors, Fibroblast Growth Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0036-8075
- Volume :
- 259
- Issue :
- 5103
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 8456318
- Full Text :
- https://doi.org/10.1126/science.8456318