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J Biol Chem, Vol. 273, Issue 34, 21439-21442, August 21, 1998

COMMUNICATION
The Core Protein of the Chondroitin Sulfate Proteoglycan Phosphacan Is a High-affinity Ligand of Fibroblast Growth Factor-2 and Potentiates Its Mitogenic Activity

Peter Milev, Hubert Monnerie, Susanna Popp^¶, Renée K. Margolis^¶, and Richard U. Margolis

From the  Department of Pharmacology, New York University Medical Center, New York, New York 10016 and the ^¶ Department of Pharmacology, State University of New York, Health Science Center, Brooklyn, New York 11203

Using a radioligand binding assay we have demonstrated that phosphacan, a chondroitin sulfate proteoglycan of nervous tissue that also represents the extracellular domain of a receptor-type protein tyrosine phosphatase, shows saturable, reversible, high-affinity binding (K_d ~6 nM) to fibroblast growth factor-2 (FGF-2). Binding was reduced by only ~35% following chondroitinase treatment of the proteoglycan, indicating that the interaction is mediated primarily through the core protein rather than the glycosaminoglycan chains. Immunocytochemical studies also showed an overlapping localization of FGF-2 and phosphacan in the developing central nervous system. At concentrations of 10 µg protein/ml, both native phosphacan and the core protein obtained by chondroitinase treatment potentiated the mitogenic effect of FGF-2 (5 ng/ml) on NIH/3T3 cells by 75-90%, which is nearly the same potentiation as that produced by heparin at an equivalent concentration. Although studies on the role of proteoglycans in mediating the binding and mitogenic effects of FGF-2 have previously focused on cell surface heparan sulfate, our results indicate that the core protein of a chondroitin sulfate proteoglycan may also regulate the access of FGF-2 to cell surface signaling receptors in nervous tissue.

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Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

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