The mitogenic signaling pathway for fibroblast growth factor-2 involves the tyrosine phosphorylation of cyclin D2 in MCF-7 human breast cancer cells
Identifieur interne : 000D51 ( Istex/Curation ); précédent : 000D50; suivant : 000D52The mitogenic signaling pathway for fibroblast growth factor-2 involves the tyrosine phosphorylation of cyclin D2 in MCF-7 human breast cancer cells
Auteurs : Anne-Sophie Vercoutter-Edouart [France] ; Jérôme Lemoine [France] ; Chanel E. Smart [Australie] ; Victor Nurcombe [Australie] ; Bénoni Boilly [France] ; Jean-Philippe Peyrat [France] ; Hubert Hondermarck [France]Source :
- FEBS Letters [ 0014-5793 ] ; 2000.
Descripteurs français
- Wicri :
- topic : Spectrométrie.
English descriptors
- KwdEn :
- Biol, Breast cancer cells, Cascade, Cell cycle, Cell lysates, Cyclin, Digestion, Feb, Fgfr, Formic acid, Frs2, Growth factor, Growth factors, Herbimycin, Immunoblotting, Immunoprecipitated, Immunoprecipitation, Inhibitor, Kinase, Kinase activation, Kinase activity, Kinase assay, Kinase cascade, Kinase pathway, Lysates, Mass spectrometry, Mitogenic, Mitogenic activity, Mitogenic stimulation, Pathway, Peptide, Pharmacological inhibition, Phosphorylated, Phosphorylation, Protein kinase, Receptor, Room temperature, Spectrometry, Trypsin, Trypsin digestion, Tyrosine, Tyrosine kinase activity, Tyrosine phosphorylation.
- Teeft :
- Biol, Breast cancer cells, Cascade, Cell cycle, Cell lysates, Cyclin, Digestion, Feb, Fgfr, Formic acid, Frs2, Growth factor, Growth factors, Herbimycin, Immunoblotting, Immunoprecipitated, Immunoprecipitation, Inhibitor, Kinase, Kinase activation, Kinase activity, Kinase assay, Kinase cascade, Kinase pathway, Lysates, Mass spectrometry, Mitogenic, Mitogenic activity, Mitogenic stimulation, Pathway, Peptide, Pharmacological inhibition, Phosphorylated, Phosphorylation, Protein kinase, Receptor, Room temperature, Spectrometry, Trypsin, Trypsin digestion, Tyrosine, Tyrosine kinase activity, Tyrosine phosphorylation.
Abstract
Abstract: Fibroblast growth factor-2 (FGF-2) is mitogenic for the human breast cancer cell line MCF-7; here we investigate some of the signaling pathways subserving this activity. FGF-2 stimulation of MCF-7 cells resulted in a global increase of intracellular tyrosine phosphorylation of proteins, particularly FGF receptor substrate-2, the protooncogene product Src and the mitogen-activated protein kinase (MAP kinase) cascade. A major increase in the tyrosine phosphorylation of a 30-kDa protein species was also found. This protein was identified as cyclin D2 by mass spectrometry after trypsin digestion. Immunoprecipitation of cyclin D2 and immunoblotting with anti-phosphotyrosine antibodies confirmed that the tyrosine phosphorylation of cyclin D2 was indeed induced by FGF-2 stimulation. In addition, pharmacological inhibition of Src (with herbimycin A and PP2), and of the MAP kinase cascade (with PD98059), confirmed that Src activity is required for the FGF-2-induced phosphorylation of cyclin D2 whereas MAP kinase activity is not. Thus, tyrosine phosphorylation of cyclin D2 may be a key regulatory target for FGF-2 signaling.
Url:
DOI: 10.1016/S0014-5793(00)01855-X
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<front><div type="abstract" xml:lang="en">Abstract: Fibroblast growth factor-2 (FGF-2) is mitogenic for the human breast cancer cell line MCF-7; here we investigate some of the signaling pathways subserving this activity. FGF-2 stimulation of MCF-7 cells resulted in a global increase of intracellular tyrosine phosphorylation of proteins, particularly FGF receptor substrate-2, the protooncogene product Src and the mitogen-activated protein kinase (MAP kinase) cascade. A major increase in the tyrosine phosphorylation of a 30-kDa protein species was also found. This protein was identified as cyclin D2 by mass spectrometry after trypsin digestion. Immunoprecipitation of cyclin D2 and immunoblotting with anti-phosphotyrosine antibodies confirmed that the tyrosine phosphorylation of cyclin D2 was indeed induced by FGF-2 stimulation. In addition, pharmacological inhibition of Src (with herbimycin A and PP2), and of the MAP kinase cascade (with PD98059), confirmed that Src activity is required for the FGF-2-induced phosphorylation of cyclin D2 whereas MAP kinase activity is not. Thus, tyrosine phosphorylation of cyclin D2 may be a key regulatory target for FGF-2 signaling.</div>
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