Publication Date:
1993-03-26
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kan, M -- Wang, F -- Xu, J -- Crabb, J W -- Hou, J -- McKeehan, W L -- New York, N.Y. -- Science. 1993 Mar 26;259(5103):1918-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉W. Alton Jones Cell Science Center, Inc. Lake Placid, NY 12946.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8456318" target="_blank"〉PubMed〈/a〉
Keywords:
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/metabolism
;
Protein-Tyrosine Kinases/chemistry/genetics/*metabolism
;
Proteoglycans/metabolism
;
Receptors, Fibroblast Growth Factor/chemistry/genetics/*metabolism
;
Recombinant Proteins/metabolism
;
Sodium Chloride/pharmacology
;
Trypsin/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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