An essential heparin-binding domain in the fibroblast growth factor receptor kinase.
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.
Kan
M
M
W. Alton Jones Cell Science Center, Inc. Lake Placid, NY 12946.
Wang
F
F
Xu
J
J
Crabb
J W
JW
Hou
J
J
McKeehan
W L
WL
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D005346:Fibroblast Growth Factors / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008239:Lysine / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010446:Peptide Fragments / Q000302:isolation & purification / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D014357:Trypsin / Q000378:metabolism
D000911:Antibodies, Monoclonal; D005346:Fibroblast Growth Factors; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin; D006497:Heparan Sulfate; D008239:Lysine; D008666:Metalloendopeptidases; D010446:Peptide Fragments; D011505:Protein-Tyrosine Kinases; D011509:Proteoglycans; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D012965:Sodium Chloride; D014357:Trypsin; C039830:peptidyl-Lys metalloendopeptidase