TY - JOUR
T1 - An essential heparin-binding domain in the fibroblast growth factor receptor kinase
AU - Kan, Mikio
AU - Wang, Fen
AU - Xu, Jianming
AU - Crabb, John W.
AU - Hou, Jinzhao
AU - McKeehan, Wallace L.
PY - 1993
Y1 - 1993
N2 - 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 K1i8K 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.
AB - 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 K1i8K 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.
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U2 - 10.1126/science.8456318
DO - 10.1126/science.8456318
M3 - Article
C2 - 8456318
AN - SCOPUS:0027192075
VL - 259
SP - 1918
EP - 1921
JO - Science (New York, N.Y.)
JF - Science (New York, N.Y.)
SN - 0036-8075
IS - 5103
ER -