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.

Possible role of protein kinase C ζ in muscarinic receptor-induced proliferation of astrocytoma cells / Guizzetti, M.; Costa, L. G.. - In: BIOCHEMICAL PHARMACOLOGY. - ISSN 0006-2952. - 60:10(2000), pp. 1457-1466. [10.1016/S0006-2952(00)00468-8]

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

Costa L. G.
2000-01-01

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.
2000
Possible role of protein kinase C ζ in muscarinic receptor-induced proliferation of astrocytoma cells / Guizzetti, M.; Costa, L. G.. - In: BIOCHEMICAL PHARMACOLOGY. - ISSN 0006-2952. - 60:10(2000), pp. 1457-1466. [10.1016/S0006-2952(00)00468-8]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2885079
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