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 journalArticlepeer-review

53 Scopus citations


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
Issue number1-2
StatePublished - Feb 28 2003
Externally publishedYes


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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology


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