Neuron
Volume 12, Issue 6, June 1994, Pages 1207-1221
Journal home page for Neuron

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

https://doi.org/10.1016/0896-6273(94)90438-3Get rights and content

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.

References (103)

  • R.J. Davis

    The mitogen-activated protein kinase signal transduction pathway

    J. Biol. Chem.

    (1993)
  • F. Di Virgilio et al.

    Tumor promoter phorbol myristate acetate inhibits Ca2+ influx through voltage-gated Ca2+ channels in two secretory cell lines, PC12 and RINm5F

    J. Biol. Chem.

    (1986)
  • B. Errede et al.

    A conserved kinase cascade for MAP kinase activation in yeast

    Curr. Opin. Cell Biol.

    (1993)
  • R.S. Fiore et al.

    p42 mitogen-activated protein kinase in brain: prominent localization in neuronal cell bodies and dendrites

    Neuroscience

    (1993)
  • J.L. Franklin et al.

    Suppression of programmed neuronal death by sustained elevation of cytoplasmic calcium

    Trends Neurosci.

    (1992)
  • P. Gass et al.

    Regionally selective stimulation of mitogen activated protein (MAP) kinase tyrosine phosphorylation after generalized seizures in the rat brain

    Neurosci. Lett.

    (1993)
  • D.D. Ginty et al.

    Transsynaptic regulation of gene expression

    Curr. Opin. Neurobiol.

    (1992)
  • I. Griswold-Prenner et al.

    Mitogen-activated protein kinase regulates the epidermal growth factor receptor through activation of atyrosine phosphatase

    J. Biol. Chem.

    (1993)
  • B. Hille

    G protein-coupled mechanisms and nervous signaling

    Neuron

    (1992)
  • L.R. Howe et al.

    Activation of the MAP kinase pathway by the protein kinase raf

    Cell

    (1992)
  • X.-Y. Huang et al.

    Tyrosine kinase-dependent suppression of a potassium channel by the G protein-coupled m1 muscarinic acetylcholine receptor

    Cell

    (1993)
  • R.K. Jaiswal et al.

    Identification and characterization of a nerve growth factor-stimulated mitogen-activated protein kinase activator in PC12 cells

    J. Biol. Chem.

    (1993)
  • M.B. Kennedy

    Regulation of neuronal function by calcium

    Trends Neurosci.

    (1989)
  • J.M. Kyriakis et al.

    Mitogen regulation of c-Raf-1 protein kinase activity toward mitogen-activated protein kinase kinase

    J. Biol. Chem.

    (1993)
  • R.A. Lindberg et al.

    Dualspecificity protein kinases: will any hydroxyl do?

    Trends Biochem. Sci.

    (1992)
  • S. Matsuda et al.

    Phosphorylation of Xenopus mitogen-activated protein (MAP) kinase kinase by MAP kinase kinase kinase and MAP kinase

    J. Biol. Chem.

    (1993)
  • T.H. Murphy et al.

    L-type voltage-sensitive calcium channels mediate synaptic activation of immediate early genes

    Neuron

    (1991)
  • N.F.L. Ng et al.

    Activation of p211a1 by nerve growth factor in embryonic sensory neurons and PC12 cells

    J. Biol. Chem.

    (1993)
  • S.L. Pelech et al.

    Mitogen-activated protein kinases: versatile transducers for cell signaling

    Trends Biochem. Sci.

    (1992)
  • M.-S. Qiu et al.

    PC12 cell neuronal differentiation is associated with prolonged p2111 activity and consequent prolonged ERK activity

    Neuron

    (1992)
  • R. Seger et al.

    Human T-cell mitogen-activated protein kinase kinases are related to yeast signal transduction kinases

    J. Biol. Chem.

    (1992)
  • T.W. Sturgill et al.

    Recent progress in characterization of protein kinase cascades for phosphorylation of ribosomal protein S6

    Biochem. Biophys. Acta

    (1991)
  • S.M. Thomas et al.

    Ras is essential for nerve growth factor- and phorbol ester-induced tyrosine phosphorylation of MAP kinases

    Cell

    (1992)
  • R.W. Tsien et al.

    Multiple types of neuronal calcium channels and their selective modulation

    Trends Neurosci.

    (1988)
  • K.W. Wood et al.

    ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1, and RSK

    Cell

    (1992)
  • H. Bading et al.

    Stimulation of protein tyrosine phosphorylation by NMDA receptor activation

    Science

    (1991)
  • J.M. Baraban et al.

    Identification of p42 mitogen-activated protein kinase as a tyrosine kinase substrate activated by maximal electroconvulsive shock in hippocampus

    J. Neurochem.

    (1993)
  • M. Barbacid

    Nerve growth factor: a tale of two receptors

    Oncogene

    (1993)
  • B.P. Bean

    Classes of calcium channels in vertebrate cells

    Annu. Rev. Physiol.

    (1989)
  • J. Blenis

    Signal transduction viatheMAP kinases: proceed at your own RSK

  • T.V.P. Bliss et al.

    A synaptic model of memory: long-term potentiation in the hippocampus

    Nature

    (1993)
  • M.S. Boguski et al.

    Proteins regulating Ras and its relatives

    Nature

    (1993)
  • G.D. Borasio et al.

    ras p21 protein promotes survival and fiber outgrowth of cultured embryonic neurons

    Neuron

    (1989)
  • G.D. Borasio et al.

    Involvement of ras p21 in neurotrophininduced response of sensory, but not sympathetic neurons

    J. Cell Biol.

    (1993)
  • H.R. Bourne et al.

    The GTPase superfamily: conserved structure and molecular mechanism

    Nature

    (1991)
  • B.K. Brott et al.

    MEK2 is a kinase related to MEK1 and isdifferentially expressed in murine tissues

    Cell Growth Differen.

    (1993)
  • R. Campos-Gonzalez et al.

    Tyrosine phosphorylation of microtubule-associated protein kinase after transient ischemia in the gerbil brain

    J. Neurochem.

    (1992)
  • J.E. Chad et al.

    An enzymatic mechanism for calcium current inactivation in dialysed Helix neurones

    J. Physiol.

    (1986)
  • M.H. Cobb et al.

    Extracellular signal-regulated kinases: ERKs in progress

    Cell Reg.

    (1991)
  • C. Collin et al.

    Early enhancement of calcium currents by H-ras oncoproteins injected into Hermissenda neurons

    Science

    (1990)
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