Activation of mitogen-activated protein kinase and p70S6 kinase is not correlated with cerebellar granule cell survival

Francis James Gunn-Moore, AG Williams, NJ Thoms, JM Tavare

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56 Citations (Scopus)

Abstract

We have investigated the role of mitogen-activated protein (MAP) kinase in the survival of cerebellar granule cells in primary culture, Brain-derived neurotrophic factor (BDNF) and insulin, but not epidermal growth factor (EGF), promoted the survival of P-6 cerebellar granule neurons, BDNF promoted a sustained activation of MAP kinase, whereas that induced by EGF was only transient, Insulin promoted a small but transient activation of MAP kinase that was completely blocked by PD98059, an inhibitor of MAP kinase kinase activation, PD98059 had no effect on the insulin- or BDNF-induced survival of cerebellar granule cells, We also investigated the role of p70S6 kinase in survival. The activation of p70S6 kinase by EGF was transient, whereas BDNF and insulin promoted a sustained activation of p70S6 kinase. Rapamycin, which blocked p70S6 kinase activation, had no effect on the BDNF- or insulin-induced survival of cerebellar granule cells. We conclude that sustained activation of MAP kinase is not correlated with the survival response of cerebellar granule cells; indeed insulin-mediated survival is independent of MAP kinase. Survival of cerebellar granule cells is also independent of the activation of p70S6 kinase.

Original languageEnglish
Pages (from-to)365-369
Number of pages5
JournalBiochemical Journal
Volume324
Publication statusPublished - 1 Jun 1997

Keywords

  • NERVE GROWTH-FACTOR
  • SUSTAINED ACTIVATION
  • NEUROTROPHIC FACTOR
  • SIGNALING PATHWAYS
  • MESSENGER-RNA
  • PC12 CELLS
  • NEURONS
  • INSULIN
  • DIFFERENTIATION
  • BRAIN

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