Cell membrane GM 1 ganglioside is a functional coreceptor for fibroblast growth factor 2
| Autor: | Elena Tanghetti, Chiara Urbinati, Patrizia Dell'Era, Marco Presta, Hugues Lortat-Jacob, Marco Rusnati |
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| Přispěvatelé: | Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA) |
| Rok vydání: | 2002 |
| Předmět: |
Cholera Toxin
Cell division medicine.medical_treatment Cell MESH: Cricetinae CHO Cells G(M1) Ganglioside MESH: Receptors Fibroblast Growth Factor Biology Fibroblast growth factor Cell membrane 03 medical and health sciences 0302 clinical medicine MESH: CHO Cells Cricetinae medicine Animals MESH: Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Cholera Toxin MESH: Tetradecanoylphorbol Acetate 030304 developmental biology 0303 health sciences Multidisciplinary Ganglioside MESH: Fibroblast Growth Factor 2 integumentary system MESH: G(M1) Ganglioside Cell growth Growth factor Chinese hamster ovary cell Biological Sciences Receptors Fibroblast Growth Factor Molecular biology medicine.anatomical_structure embryonic structures Tetradecanoylphorbol Acetate MESH: Cell Division Fibroblast Growth Factor 2 Cell Division 030217 neurology & neurosurgery |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2002, 99 (7), pp.4367-72. ⟨10.1073/pnas.072651899⟩ Proceedings of the National Academy of Sciences of the United States of America, 2002, 99 (7), pp.4367-72. ⟨10.1073/pnas.072651899⟩ |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.072651899 |
| Popis: | 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 B 1 , 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 GM 1 -binding cholera toxin B subunit (CTB). Conversely, overloading of endothelial GM 7373 cell membranes with exogenous GM 1 causes a 10-fold increase of the mitogenic potency of FGF2. 125 I-FGF2 binds to cell membrane GM 1 ( K d = 3 nM) in complex ganglioside/heparan sulfate-deficient Chinese hamster ovary (CHO)-K1-pgsA745 cell mutants that were overloaded with exogenous GM 1 . Moreover, FGF2 competes with FITC-CTB for the binding to cell membrane GM 1 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, GM 1 -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 GM 1 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. |
| Databáze: | OpenAIRE |
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