NDLI: Cell membrane GM1 ganglioside is a functional coreceptor for fibroblast growth factor 2.

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Cell membrane GM1 ganglioside is a functional coreceptor for fibroblast growth factor 2.

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Cell membrane GM1 ganglioside is a functional coreceptor for fibroblast growth factor 2.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lortat-jacob, Hugues Presta, Marco Urbinati, Chiara Tanghetti, Elena Dell'era, Patrizia Rusnati, Marco
Description	Author Affiliation: Rusnati M ( Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, 25123 Brescia, Italy.);
Abstract	Free gangliosides bind fibroblast growth factor 2 (FGF2), thus preventing cell interaction and biological activity of the growth factor in endothelial cells. Here we investigated the role of cell-associated gangliosides in mediating the biological activity of FGF2. Treatment of endothelial cells of different origin with the ganglioside biosynthesis inhibitors fumonisin B1, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol or D-1-threo-1-phenyl-2-hexa-decanoylamino-3-pyrrolidino-1-propanol-HCl, impairs their capacity to proliferate when exposed to FGF2. Also, the mitogenic activity of FGF2 is inhibited by the GM1-binding cholera toxin B subunit (CTB). Conversely, overloading of endothelial GM 7373 cell membranes with exogenous GM1 causes a 10-fold increase of the mitogenic potency of FGF2. 125I-FGF2 binds to cell membrane GM1 (K(d) = 3 nM) in complex ganglioside/heparan sulfate-deficient Chinese hamster ovary (CHO)-K1-pgsA745 cell mutants that were overloaded with exogenous GM1. Moreover, FGF2 competes with FITC-CTB for the binding to cell membrane GM1 in different CHO cell lines independently of their capacity to express heparan sulfate proteoglycans. Conversely, CTB inhibits cell proliferation triggered by FGF2 in CHO cells overexpressing the tyrosine kinase FGF receptor 1. Finally, GM1-overloading confers to FGF receptor 1-transfected, complex ganglioside-deficient CHO-K1 cell mutants the capacity to proliferate when stimulated by FGF2. This proliferation is inhibited by CTB. Cell proliferation triggered by serum or by phorbol 12-myristate 13-acetate is instead independent of the cell membrane ganglioside milieu. In conclusion, cell membrane GM1 binds FGF2 and is required for the mitogenic activity of the growth factor. Our data indicate that cell-associated gangliosides may act as functional FGF2 co-receptors in different cell types.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	7
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Fibroblast Growth Factor 2 Metabolism G(M1) Ganglioside Receptors, Fibroblast Growth Factor Animals CHO Cells Cell Division Drug Effects Cholera Toxin Cricetinae Pharmacology Tetradecanoylphorbol Acetate Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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