TY - JOUR
T1 - Possible role of protein kinase C ζ in muscarinic receptor-induced proliferation of astrocytoma cells
AU - Guizzetti, Marina
AU - Costa, Lucio G.
N1 - Funding Information:
This work was supported, in part, by Grants AA-08154 and ES-07033 from the National Institutes of Health. We thank Dr. Terrance Kavanagh and Collin White for help with the confocal microscope
PY - 2000/11/15
Y1 - 2000/11/15
N2 - 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.
AB - 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.
KW - 132-1N1 astrocytoma cells
KW - Cell proliferation
KW - Muscarinic receptor
KW - Protein kinase C ζ
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U2 - 10.1016/S0006-2952(00)00468-8
DO - 10.1016/S0006-2952(00)00468-8
M3 - Article
C2 - 11020447
AN - SCOPUS:0034670168
SN - 0006-2952
VL - 60
SP - 1457
EP - 1466
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 10
ER -