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

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MAP Kinase Kinase Kinases
Mitogen-Activated Protein Kinases
Calcium
Membranes
Calcium Signaling
L-Type Calcium Channels
Intracellular Membranes
Guanine Nucleotides
PC12 Cells
Mitogen-Activated Protein Kinase Kinases
Calcium Channels
Nervous System
Carrier Proteins
Cell Membrane
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Membrane depolarization and calcium influx stimulate MEK and MAP kinase via activation of Ras. / Rosen, Laura B.; Ginty, David D.; Weber, Michael J.; Greenberg, Michael E.

In: Neuron, Vol. 12, No. 6, 1994, p. 1207-1221.

Research output: Contribution to journalArticle

Rosen, Laura B. ; Ginty, David D. ; Weber, Michael J. ; Greenberg, Michael E. / Membrane depolarization and calcium influx stimulate MEK and MAP kinase via activation of Ras. In: Neuron. 1994 ; Vol. 12, No. 6. pp. 1207-1221.
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