Membrane depolarization and calcium influx stimulate MEK and MAP kinase via activation of Ras

Laura B. Rosen, David D. Ginty, Michael J. Weber, Michael E. Greenberg

Research output: Contribution to journalArticle

Abstract

A pathway by which calcium influx through voltagesensitive calcium channels leads to mitogen-activated protein kinase (MAPK) activation has been characterized. In PC12 cells, membrane depolarization leading to calcium influx through L-type calcium channels activates the dual specificity MAPK kinase MEK1, which phosphorylates and activates MAPK. Calcium influx leads within 30 s to activation of the small guanine nucleotide-binding protein Ras. Moreover, activation of MAPK in response to calcium influx is inhibited by the dominant negative mutant RasAsn17, indicating that Ras activity is required for calcium signaling to MAPK. Ras is also activated by release of calcium from intracellular stores and by membrane depolarization of primary cortical neurons. The pleiotropic regulatory potential of both Ras and the MAPK pathway suggests that they may be central mediators of calcium signaling in the nervous system.

Original languageEnglish (US)
Pages (from-to)1207-1221
Number of pages15
JournalNeuron
Volume12
Issue number6
DOIs
StatePublished - 1994
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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