The mitogenic signaling pathway for fibroblast growth factor‐2 involves the tyrosine phosphorylation of cyclin D2 in MCF‐7 human breast cancer cells

FEBS Letters

Hondermarck, Hubert²  Lemoine, Jérôme¹  Peyrat, Jean-Philippe³  Smart, Chanel E.⁴  Nurcombe, Victor⁴  Boilly, Bénoni²  Vercoutter-Edouart, Anne-Sophie² 

[1] Laboratoire de Chimie Biologique, UMR 8576 CNRS, Université des Sciences et Technologies de Lille, Villeneuve d'Ascq Cedex, France;Equipe Facteurs de Croissance, Laboratoire de Biologie du Développement, UPRES-EA1033, batiment SN3, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France;Laboratoire d'Oncologie Moléculaire Humaine, Centre de Lutte Contre le Cancer, Lille, France;Department of Anatomical Sciences, University of Queensland 4072 Brisbane, Qld., Australia

关键词: Fibroblast growth factor-2;    Signaling pathway;    Cyclin D2;    Breast cancer cell;    ERK;    extracellular regulated kinase;    FGF;    fibroblast growth factor;    FGFR;    fibroblast growth factor receptor;    FRS2;    fibroblast growth factor receptor substrate-2;    MALDI-TOF;    matrix-assisted laser desorption ionization-time of flight;    MAP kinase;    mitogen-activated protein kinase;    MEK;    MAPK/ERK kinase;    PI3 kinase;    phosphatidyl-inositol 3′ kinase;    PMA;    phorbol 12-myristate 13-acetate;   

DOI  :  10.1016/S0014-5793(00)01855-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown