Activation of the MAP kinase cascade by exogenous calcium-sensing receptor

Susan A. Hobson, Jay Wright, Fred Lee, Scott E. McNeil, Timothy Bilderback, Karin D. Rodland

    Research output: Contribution to journalArticle

    53 Scopus citations

    Abstract

    In Rat-1 fibroblasts and ovarian surface epithelial cells, extracellular calcium induces a proliferative response which appears to be mediated by the G-protein coupled calcium-sensing receptor (CaR), as expression of the nonfunctional CaR-R795W mutant inhibits both thymidine incorporation and activation of the extracellular-regulated kinase (ERK) in response to calcium. In this report we utilized CaR-transfected HEK293 cells to demonstrate that functional CaR is necessary and sufficient for calcium-induced ERK activation. CaR-dependent ERK activation was blocked by co-expression of the Ras dominant-negative mutant, Ras N17, and by exposure to the phosphatidyl inositol 3′ kinase inhibitors wortmannin and LY294002. In contrast to Rat-1 fibroblasts, CaR-mediated in vitro kinase activity of ERK2 was unaffected by tyrosine kinase inhibitor herbimycin in CaR-transfected HEK293 cells. These results suggest that usage of distinct pathways downstream of the CaR varies in a cell-type specific manner, suggesting a potential mechanism by which activation of the CaR could couple to distinct calcium-dependent responses.

    Original languageEnglish (US)
    Pages (from-to)189-198
    Number of pages10
    JournalMolecular and Cellular Endocrinology
    Volume200
    Issue number1-2
    DOIs
    StatePublished - Feb 28 2003

    Keywords

    • Calcium-sensing receptor
    • HEK293 cells
    • MAP Kinase
    • PI3′ Kinase
    • Proliferation

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Endocrinology

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  • Cite this

    Hobson, S. A., Wright, J., Lee, F., McNeil, S. E., Bilderback, T., & Rodland, K. D. (2003). Activation of the MAP kinase cascade by exogenous calcium-sensing receptor. Molecular and Cellular Endocrinology, 200(1-2), 189-198. https://doi.org/10.1016/S0303-7207(01)00749-3