The core protein of the chondroitin sulfate proteoglycan phosphacan is a high-affinity ligand of fibroblast growth factor-2 and potentiates its mitogenic activity.
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 (Kd approximately 6 nM) to fibroblast growth factor-2 (FGF-2). Binding was reduced by only approximately 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 microg 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.
Department of Pharmacology, New York University Medical Center, New York, New York 10016, USA.
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Milev
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Monnerie
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Popp
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Margolis
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Margolis
D016475:3T3 Cells; D000818:Animals; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D002810:Chondroitinases and Chondroitin Lyases / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D007700:Kinetics; D037181:Lectins, C-Type; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058580:Neurocan; D011485:Protein Binding; D051381:Rats; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5
D011508:Chondroitin Sulfate Proteoglycans; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins; D058580:Neurocan; D016222:Fibroblast Growth Factor 2; C076817:NCAN protein, human; C516895:PTPRZ1 protein, human; C516896:Ptprz1 protein, mouse; C516897:Ptprz1 protein, rat; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D002810:Chondroitinases and Chondroitin Lyases