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) [Mos catelli (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 studie s demonstrated that acidic FGF (aFGF) and basic FGF (bFGF) bind to ide ntical 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 diff ers 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 d issociates from the FGFR at least 10-fold slower than aFGF, whereas, f ollowing removal of cell surface heparan sulfate proteoglycans by hepa rinase treatment, the dissociation rate of both FGFs is similar and ra pid. These results support the concept that cell surface heparan sulfa te proteoglycans stabilize the interaction of FGF with FGFR, possibly by the formation of a ternary complex. (C) 1995 Wiley-Liss, Inc.