Abstract
It is now widely accepted that tumour-promoting phorbol esters activate a Ca2+- and phospholipid-dependent protein kinase (protein kinase C) both in vitro and in intact cells1–3, and that the kinase represents a major cellular phorbol ester-binding protein. The phorbol esters act as analogues of diacylglycerol, a natural regulator of protein kinase C, and stabilize the membrane-association of the kinase. Although other molecular targets may exist, protein kinase C activation is probably important in mediating the diverse responses of cultured cells to phorbol esters and in promoting in vivo tumours. The enzyme comprises a family of closely related proteins4–7 and has been detected in extracts from mouse epidermal cells8–10, the likely targets for two-stage car-cinogenesis in mouse skin. In this report we show that application of a single dose of TPA (12-O-tetradecanoyl phorbol-13-acetate) to mouse skin results in a rapid and complete loss of protein kinase C activity which is maintained for 3–4 days. This is associated with a loss of immunologically detectable protein kinase C and the accumulation of a smaller protein detectable by antibodies recognizing the regulatory domain of protein kinase C.
Similar content being viewed by others
References
1. Nishizuka, Y. Nature 308, 693-697 (1984). 2. Nishizuka, Y. Science 233, 305-312 (1986). 3. Sekar, M. C. & Hokin, L. E. J. Membrane Biol. 89, 193-210 (1986). 4. Coussens, L. el al. Science 233, 859-866 (1986). 5. Knopf, J. et al. Cell 46, 491-502 (1986). 6. Ono, Y. et al. Science 236, 1116-1122 (1987). 7. Mousey, G. M. et al. Proc. natn. Acad. Sci. U.S.A. 84, 1065-1069 (1987). 8. Garte, S. J., Edinger, F. & Mufson, R. A. Cancer Lett. 29, 215-221 (1985). 9. Gschwendt, M. et al. Biochem. biophys. Res. Commun. 124, 63-68 (1984). 10. Kumar, R. & Holian, O. J. invest. Dermatol. 86, 316-320 (1986). 11. Parker, P. J. et al. Science 233, 853-859 (1986). 12. Stabel, S. et al. J. cell. Physiol. 130, 111-117 (1987). 13. Girard, P. R., Mazzei, G. J. & Kuo, J. F. / biol. Chem. 261, 370-375 (1986). 14. Cambier, J. C. et al. Nature 327, 629-632 (1987). 15. Murray, A. W., Fournier, A. & Hardy, S. Trends biochem. Sci. 134, 53-54 (1987). 16. Chida, K., Kato, N. & Kuroki, T. /. biol. Chem. 261, 13013-13018 (1986). 17. Tapley, P. M. & Murray, A. W. Biochem. biophys. Res. Commun. 118, 835-841 (1984). 18. Win, J. J. & Roskoski, R. Jr Analyt. Biochem. 66, 253-258 (1975). 19. Lowry, O. H., Rosenbrough, N. J., Farr, A. L. & Randall, R. J. /. biol. Chem. 193, 265-275 (1951). 20. Laemmli, U. K. Nature 227, 680-685 (1970). 21. Burnette, W. N. Analyt. Biochem. 112, 195-203 (1981). 22. Wolf, M., Cuatrecasas, P. & Sahyoun, N. J. biol. Chem. 260, 15718-15722 (1985).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fournier, A., Murray, A. Application of phorbol ester to mouse skin causes a rapid and sustained loss of protein kinase C. Nature 330, 767–769 (1987). https://doi.org/10.1038/330767a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/330767a0
- Springer Nature Limited
This article is cited by
-
Tumour necrosis factor-α mediates tumour promotion via a PKCα- and AP-1-dependent pathway
Oncogene (2002)
-
Regression, proliferation and development of lip papillomas in wild white suckers,Catostomus commersoni, held in the laboratory
Environmental Biology of Fishes (1994)
-
Regulation of protein kinase C and role in cancer biology
Cancer and Metastasis Reviews (1994)
-
Further identification of protein kinase C isozymes in mouse epidermis
Journal of Cancer Research and Clinical Oncology (1993)
-
1-Dehydro-melengestrol acetate inhibitis the growth and protein kinase C activity of androgen-independent Dunning rat prostatic tumors
Cancer Chemotherapy and Pharmacology (1993)