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The mitogenic signaling pathway for fibroblast growth factor‐2 involves the tyrosine phosphorylation of cyclin D2 in MCF‐7 human breast cancer cells
Author(s) -
Vercoutter-Edouart Anne-Sophie,
Lemoine Jérôme,
Smart Chanel E.,
Nurcombe Victor,
Boilly Béi,
Peyrat Jean-Philippe,
Hondermarck Hubert
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01855-x
Subject(s) - cyclin d , tyrosine phosphorylation , proto oncogene tyrosine protein kinase src , platelet derived growth factor receptor , cancer research , protein tyrosine phosphatase , tyrosine kinase , receptor tyrosine kinase , phosphorylation , cyclin dependent kinase complex , cyclin a , microbiology and biotechnology , biology , cyclin a2 , cyclin dependent kinase 2 , chemistry , signal transduction , biochemistry , cyclin d1 , protein kinase a , growth factor , cell cycle , cell , receptor
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.