Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor.
The role of low affinity, heparin-like binding sites for basic fibroblast growth factor (bFGF) was investigated in CHO cells mutant in their metabolism of glycosaminoglycans. Heparan sulfate-deficient mutants transfected to express a cloned mouse FGF receptor cDNA are not able to bind bFGF. It is demonstrated that free heparin and heparan sulfate can reconstitute a low affinity receptor that is, in turn, required for the high affinity binding of bFGF. These studies suggest that the low affinity receptor is an accessory molecule required for binding of bFGF to the high affinity site. Such an obligatory interaction of low and high affinity FGF receptors suggests a physiological role for heparin-like, low affinity receptors and constitutes a novel mechanism for the regulation of growth factor-receptor interactions.
Yayon
A
A
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Klagsbrun
M
M
Esko
J D
JD
Leder
P
P
Ornitz
D M
DM
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000494:pharmacology; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010053:Ovary; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D011508:Chondroitin Sulfate Proteoglycans; D016222:Fibroblast Growth Factor 2; D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin; D006497:Heparan Sulfate; D015345:Oligonucleotide Probes; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins