Acidic and basic fibroblast growth factor bind with differing affinity to the same heparan sulfate proteoglycan on BALB/c 3T3 cells: implications for potentiation of growth factor action by heparin.
Heparan sulfate proteoglycans on the cell surface act as low affinity binding sites for acidic and basic fibroblast growth factor (FGF) [Moscatelli (1987): J Cell Physiol 131:123-130] and play an important role in the interaction of FGF with the FGF receptor (FGFR). In this study, several aspects of the interaction of FGFs with cell surface heparan sulfate proteoglycans were examined. Reciprocal cross blocking studies demonstrated that acidic FGF (aFGF) and basic FGF (bFGF) bind to identical or closely associated heparan sulfate motifs on BALB/c 3T3 cell surface heparan sulfate proteoglycans. However, the binding affinity of the two growth factors for these heparan sulfate proteoglycans differs considerably, competition binding data indicating that aFGF has a 4.7-fold lower affinity than bFGF for 3T3 heparan sulfate proteoglycan. Subsequent studies of dissociation kinetics demonstrated that bFGF dissociates from the FGFR at least 10-fold slower than aFGF, whereas, following removal of cell surface heparan sulfate proteoglycans by heparinase treatment, the dissociation rate of both FGFs is similar and rapid. These results support the concept that cell surface heparan sulfate proteoglycans stabilize the interaction of FGF with FGFR, possibly by the formation of a ternary complex.
Brown
K J
KJ
Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra.
Hendry
I A
IA
Parish
C R
CR
D016475:3T3 Cells; D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin / Q000378:metabolism*; D019763:Heparin Lyase; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D051379:Mice; D011133:Polysaccharide-Lyases / Q000378:metabolism; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D013997:Time Factors
D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin; D019763:Heparin Lyase; D006497:Heparan Sulfate; D011133:Polysaccharide-Lyases; D011509:Proteoglycans; D017468:Receptors, Fibroblast Growth Factor