Possible role of protein kinase C ζ in muscarinic receptor-induced proliferation of astrocytoma cells

Marina Guizzetti, Lucio G. Costa

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Recent studies have shown that protein kinase C ζ (PKC ζ) is part of a pathway that plays a key role in a wide range of physiological processes including mitogenesis, cell survival, and transcriptional regulation. Most studies on PKC ζ have been done by stimulating cells with tyrosine kinase receptor agonists, or by transfecting the cells with either constitutively active PKC ζ or negative mutants of PKC ζ. Less is known about the ability of endogenous G-protein-coupled receptors to generate a mitogenic signal through activation of endogenous PKC ζ. In the present paper, we showed that in 123-1N1 human astrocytoma cells, which express the G-protein-coupled M2, M3, and M5 muscarinic receptors, PKC ζ is activated by carbachol in a concentration-dependent manner, resulting in the translocation of PKC ζ from the cytoplasm to granules in the perinuclear region. The effect of carbachol was long-lasting (up to 24 hr) and appeared to be mediated by activation of M3 muscarinic receptors. A selective PKC ζ inhibitor peptide (peptide Z) inhibited PKC ζ translocation as well as carbachol-induced DNA synthesis. Inhibition of both phosphatidylinositol 3-kinase and phospholipase D decreased carbachol-induced [3H]thymidine incorporation and blocked carbachol-induced PKC ζ translocation, suggesting an involvement of both pathways in these effects. (C) 200 Elsevier Science.

Original languageEnglish (US)
Pages (from-to)1457-1466
Number of pages10
JournalBiochemical Pharmacology
Volume60
Issue number10
DOIs
StatePublished - Nov 15 2000

Keywords

  • 132-1N1 astrocytoma cells
  • Cell proliferation
  • Muscarinic receptor
  • Protein kinase C ζ

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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