Protein kinase C activation of physiological processes in human neutrophils at vanishingly small cytosolic Ca2+ levels (original) (raw)
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- Published: 23 August 1984
Nature volume 310, pages 691–693 (1984)Cite this article
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Abstract
It has long been assumed that a rise in cytosolic free Ca2+, [Ca2+]i, is a necessary and sufficient event for the stimulation of a variety of cellular processes1,2. The development of a technique which allows monitoring of [Ca2+]i in small intact cells3 has led to a critical revision of this simple postulate4–7. We have recently shown that in neutrophils, Ca2+-ionophore-induced elevations of [Ca2+]i, quantitatively similar to those caused by chemotatic peptides, are ineffective in stimulating cell responses8, which suggests that an additional signal is required for receptor-mediated activation. Here we show that subthreshold concentrations of phorbol myristate acetate (PMA) and of a Ca2+ ionophore can quantitatively mimic the effect of a physiological agonist. However, PMA at higher concentrations can trigger NADPH-oxidase activity, exocytosis and protein phosphorylation, even when [Ca2+]i is lowered 10–20 times below the normal resting level. These results strongly suggest that activation of protein kinase C is sufficient, by itself, to induce NADPH-oxidase activation and exocytosis of secondary granules in neutrophils.
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References
- Rubin, R. P. Calcium and Cellular Secretion (Plenum, New York, 1982).
Book Google Scholar - Gomperts, B. D. in Biological Membranes Vol. 5 (ed. Chapman, D.) 284–340 (Academic, New York, 1984).
Google Scholar - Tsien, R. Y., Pozzan, T. & Rink, T. J., J. Cell Biol. 94, 325–334 (1982).
Article CAS PubMed Google Scholar - Rink, T. J., Smith, S. W. & Tsien, R. Y. FEBS Lett. 148, 21–26 (1982).
Article CAS PubMed Google Scholar - Rink, T. J., Sanchez, A. & Hallam, I. J. Nature 305, 317–319 (1983).
Article ADS CAS PubMed Google Scholar - Pozzan, T., Arslan, P., Tsien, R. Y. & Rink, T. J. J. Cell Biol. 94, 335–340 (1982).
Article CAS PubMed Google Scholar - Meldolesi, J., Huttner, W. B., Tsien, R. Y. & Pozzan, T. Proc. natn. Acad. Sci. U.S.A. 81, 620–624 (1984).
Article ADS CAS Google Scholar - Pozzan, T., Lew, D. P., Wollheim, C. B. & Tsien, R. Y. Science 221, 1413–1415 (1983).
Article ADS CAS PubMed Google Scholar - Nishizuka, Y. Trends biochem. Sci. 8, 13–16 (1981).
Article Google Scholar - Kajikawa, N. et al. Biochem. biophys. Res. Commun. 116, 743–750 (1983).
Article CAS PubMed Google Scholar - Kaibuchi, K. et al. J. biol. Chem. 258, 6701–6704 (1983).
CAS PubMed Google Scholar - Michell, R. Trends biochem. Sci. 8, 263–265 (1983).
Article CAS Google Scholar - Yin, H. L. & Stossel, T. P. J. biol. Chem. 255, 9490–9493 (1980).
CAS PubMed Google Scholar - Klee, C. B., Crouch, T. H. & Krinks, M. H. Proc. natn. Acad. Sci. U.S.A. 76, 6270–6273 (1979).
Article ADS CAS Google Scholar - Pershandsingh, H. A., Landt, M. & McDonald, J. M. J. biol. Chem. 255, 8983–8986 (1980).
Google Scholar - Niggli, V., Adunyah, E. S. & Carafoli, E. J. biol. Chem. 256, 8588–8592 (1981).
CAS PubMed Google Scholar - Gillis, J. M., Thomason, D., Lefevre, J. & Kretsinger, R. H. J. Muscle Res. Cell Motility 3, 377–398 (1982).
Article CAS Google Scholar - Burger, D., Stein, E. A. & Cox, J. A. J. biol. Chem. 258, 14733–14739 (1983).
CAS PubMed Google Scholar - Castagna, M. et al. J. biol. Chem. 257, 7847–7851 (1982).
CAS PubMed Google Scholar - Schneider, C., Zanetti, M. & Romeo, D. FEBS Lett. 127, 4–8 (1981).
Article CAS PubMed Google Scholar - Lew, D. P. & Stossel, T. P. J. clin. Invest. 67, 1–9 (1981).
Article CAS PubMed PubMed Central Google Scholar - Estensen, R. D., White, J. G. & Holmes, B. Nature 248, 347–348 (1974).
Article ADS CAS PubMed Google Scholar - Gunther, G. R. J. biol. Chem. 256, 12040–12045 (1981).
CAS PubMed Google Scholar - Niedel, J. E., Kuhn, L. J. & Vandenbark, G. R. Proc. natn. Acad. Sci. U.S.A. 8, 263–265 (1983).
Google Scholar - Sando, J. J. et al. Fedn Proc. 42, 2250–2253 (1983).
Google Scholar - Helfman, D. M., Appelbaum, B. D., Vogler, W. R. & Kuo, J. F. Biochem. biophys. Res. Commun. 111, 847–853 (1983).
Article CAS PubMed Google Scholar
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Authors and Affiliations
- CNR Unit for the Study of Physiology of Mitochondria, c/o Institute of General Pathology, Via Loredan 16, 35100, Padova, Italy
F. Di Virgilio & T. Pozzan - Infectious Diseases Unit, Department of Internal Medicine, University of Geneva, CH-1211, Geneva, 4, Switzerland
D. P. Lew
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- F. Di Virgilio
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Di Virgilio, F., Lew, D. & Pozzan, T. Protein kinase C activation of physiological processes in human neutrophils at vanishingly small cytosolic Ca2+ levels.Nature 310, 691–693 (1984). https://doi.org/10.1038/310691a0
- Received: 10 April 1984
- Accepted: 14 June 1984
- Issue Date: 23 August 1984
- DOI: https://doi.org/10.1038/310691a0