Nature 308, 693 - 698 (19 April 1984); doi:10.1038/308693a0

The role of protein kinase C in cell surface signal transduction and tumour promotion

Yasutomi Nishizuka

Department of Biochemistry, Kobe University School of Medicine, Kobe 650, Japan, and Department of Cell Biology, National Institute for Basic Biology, Okazaki 444, Japan

Protein kinase C has a crucial role in signal transduction for a variety of biologically active substances which activate cellular functions and proliferation. When cells are stimulated, protein kinase C is transiently activated by diacylglycerol which is produced in the membrane during the signal-induced turnover of inositol phospholipids. Tumour-promoting phorbol esters, when intercalated into the cell membrane, may substitute for diacylglycerol and permanently activate protein kinase C. The enzyme probably serves as a receptor for the tumour promoters. Further exploration of the roles of this enzyme may provide clues for understanding the mechanism of cell growth and differentiation.

References

1.	Inoue, M., Kishimoto, A., Takai, Y. & Nishizuka, Y. J. biol. Chem. 252, 7610−7616 (1977). | PubMed | ISI | ChemPort |
2.	Takai, Y. et al. J. biol. Chem. 254, 3692−3695 (1979). | PubMed | ISI | ChemPort |
3.	Takai, Y., Kishimoto, A., Kikkawa, U., Mori, T. & Nishizuka, Y. Biochem. biophys. Res. Commun. 91, 1218−1224 (1979). | PubMed | ISI | ChemPort |
4.	Kishimoto, A., Takai, Y., Mori, T., Kikkawa, U. & Nishizuka, Y. J. biol. Chem. 255, 2273−2276 (1980). | PubMed | ISI | ChemPort |
5.	Nishizuka, Y. Molec. Biol. Biochem. Biophys. 32, 113−135 (1980). | ChemPort |
6.	Nishizuka, Y. Phil. Trans. R. Soc. B. 302, 101−112 (1983). | ISI | ChemPort |
7.	Nishizuka, Y. & Takai, Y. Cold Spring Harb. Conf. Cell Proliferation 8, 237−249 (1981). | ChemPort |
8.	Nishizuka, Y. Trends biochem. Sci. 8, 13−16 (1983). | Article | ISI | ChemPort |
9.	Takai, Y., Kishimoto, A. & Nishizuka, Y. in Calcium and Cell Function Vol. 2 (ed. Cheung, W. Y.) 385−412 (Academic, New York, 1982). | ChemPort |
10.	Takai, Y., Kikkawa, U., Kaibuchi, K. & Nishizuka, Y. Adv. Cyclic Nucleotide Res. (in the press).
11.	Nishizuka, Y., Takai, Y., Kishimoto, A., Kikkawa, U. & Kaibuchi, K. Recent Prog. Horm. Res. 40, 301−345 (1984). | PubMed | ISI | ChemPort |
12.	Kaibuchi, K., Takai, Y. & Nishizuka, Y. J. biol. Chem. 256, 7146−7149 (1981). | PubMed | ISI | ChemPort |
13.	Mori, T., Takai, Y., Minakuchi, R., Yu, B. & Nishizuka, Y. J. biol. Chem. 255, 8378−8380 (1980). | PubMed | ISI | ChemPort |
14.	Wise, B. C. et al. J. biol. Chem. 257, 8489−8495 (1982). | PubMed | ISI | ChemPort |
15.	Kuo, J. F. et al. Proc. natn. Acad. Sci. U.S.A. 77, 7039−7043 (1980). | ChemPort |
16.	Kikkawa, U., Takai, Y., Minakuchi, R., Inohara, S. & Nishizuka, Y. J. biol. Chem. 257, 13341−13348 (1982). | PubMed | ChemPort |
17.	Kishimoto, A., Kajikawa, N., Shiota, M. & Nishizuka, Y. J. biol. Chem. 258, 1156−1164 (1983). | PubMed | ISI | ChemPort |
18.	Nimmo, H. G. & Cohen, P. Adv. Cyclic Nucleotide Res. 8, 145−266 (1977). | PubMed | ChemPort |
19.	Krebs, E. G. & Beavo, J. A. A. Rev. Biochem. 48, 923−959 (1979). | Article | ISI | ChemPort |
20.	Michell, R. H. Biochim. biophys. Acta 415, 81−147 (1975). | Article | PubMed | ISI | ChemPort |
21.	Berridge, M. J. Molec. cell. Endocr. 24, 115−140 (1981). | Article | PubMed | ISI | ChemPort |
22.	Michell, R. H., Kirk, C. J., Jones, L. M., Downes, D. P. & Creba, J. A. Phil. Trans. R. Soc. B296, 123−137 (1981). | ISI | ChemPort |
23.	Hokin, M. R. & Hokin, L. E. J. biol. Chem. 203, 967−977 (1953). | PubMed | ISI | ChemPort |
24.	Downes, P. & Michell, R. H. Cell Calcium 3, 467−502 (1982). | Article | PubMed | ISI | ChemPort |
25.	Berridge, M. J., Dawson, R. M. C., Downes, C. P., Heslop, J. P. & Irvine, R. F. Biochem. J. 212, 473−482 (1983). | PubMed | ISI | ChemPort |
26.	Abdel-Latif, A. A., Akhtar, R. A. & Hawthorne, J. N. Biochem. J. 162, 61−73 (1977). | PubMed | ChemPort |
27.	Kawahara, Y., Takai, Y., Minakuchi, R., Sano, K. & Nishizuka, Y. Biochem. biophys. Res. Commun. 97, 309−317 (1980). | PubMed | ISI | ChemPort |
28.	Sano, K., Takai, Y., Yamanishi, J. & Nishizuka, Y. J. biol. Chem. 258, 2010−2013 (1983). | PubMed | ISI | ChemPort |
29.	Lyons, R. M., Stanford, N. & Majerus, P. W. J. clin. Invest. 56, 924−936 (1975). | PubMed | ISI | ChemPort |
30.	Haslam, R. J. & Lynham, J. A. Biochem. biophys. Res. Commun. 77, 714−722 (1977). | PubMed | ISI | ChemPort |
31.	Leyasu, H., Takai, Y., Kaibuchi, K., Sawamura, M. & Nishizuka, Y. Biochem. biophys. Res. Commun. 108, 1701−1708 (1982). | PubMed |
32.	Yagi, K., Yazawa, M., Kakiuchi, S., Ohshima, M. & Uenishi, K. J. biol. Chem. 253, 1338−1340 (1978). | PubMed | ISI | ChemPort |
33.	Imaoka, T., Lynham, J. A. & Haslam, R. J. J. biol. Chem. 258, 11404−11414 (1983). | PubMed | ChemPort |
34.	Rittenhouse-Simmons, S. J. clin. Invest. 63, 580−587 (1979). | PubMed | ChemPort |
35.	Bell, R. L. & Majerus, P. W. J. biol. Chem. 255, 1790−1792 (1980). | PubMed | ISI | ChemPort |
36.	Kaibuchi, K., Sano, K., Hoshijima, M., Takai, Y. & Nishizuka, Y. Cell Calcium 3, 323−335 (1982). | Article | PubMed | ISI | ChemPort |
37.	Kaibuchi, K. et al. J. biol. Chem. 258, 6701−6704 (1983). | PubMed | ISI | ChemPort |
38.	Hecker, E. Meth. Cancer Res. 6, 439−484 (1971). | ChemPort |
39.	Weinstein, I. B., Lee, L. S., Mufson, A. & Yamasaki, H. J. supramolec. Struct. 12, 195−208 (1979). | ISI | ChemPort |
40.	Blumberg, P. M. CRC Crit. Rev. Tox. 8, 153−197 (1980). | ISI | ChemPort |
41.	Castagna, M. et al. J. biol. Chem. 257, 7847−7851 (1982). | PubMed | ISI | ChemPort |
42.	Yamanishi, J. et al. Biochem. biophys. Res. Commun. 112, 778−786 (1983). | PubMed | ISI | ChemPort |
43.	Kikkawa, U., Takai, Y., Tanaka, Y., Miyake, R. & Nishizuka, Y. J. biol. Chem. 258, 11442−11445 (1983). | PubMed | ChemPort |
44.	Dunphy, W. G., Kochenburger, R. J., Castagna, M. & Blumberg, P. M. Cancer Res. 41, 2640−2647 (1981). | PubMed | ISI | ChemPort |
45.	Horowitz, A. D., Greenebaum, E. & Weinstein, I. B. Proc. natn. Acad. Sci. U.S.A. 78, 2315−2319 (1981). | ChemPort |
46.	Solanki, V. & Slaga, T. J. Proc. natn. Acad. Sci. U.S.A. 78, 2549−2553 (1981). | ChemPort |
47.	Ashendel, C. L., Staller, J. M. & Boutwell, R. K. Biochem. biophys. Res. Commun. 111, 340−345 (1983). | PubMed | ISI | ChemPort |
48.	Sando, J. J. & Young, M. C. Proc. natn. Acad. Sci. U.S.A. 80, 2642−2646 (1983). | ChemPort |
49.	Leach, K. L., James, M. L. & Blumberg, P. M. Proc. natn. Acad. Sci. U.S.A. 80, 4208−4212 (1983). | ChemPort |
50.	Shoyab, M. & Boaze, R. Jr. Cold Spring Harb. Conf. Cell. Proliferation 11 (in the press).
51.	Delclos, K. B., Yeh, E. & Blumberg, P. M. Proc. natn. Acad. Sci. U.S.A. 80, 3054−3058 (1983). | ChemPort |
52.	Kraft, A. S., Anderson, W.B., Cooper, H. L. & Sando, J. J. J. biol. Chem. 257, 13193−13196 (1982). | PubMed | ChemPort |
53.	Shoyab, M. & Todaro, G. J. Nature 388, 451−455 (1980).
54.	Niedel, J. E., Kuhn, L. J. & Vandenbark, G. R. Proc. natn. Acad. Sci. U.S.A. 80, 36−40 (1983). | ChemPort |
55.	Kikkawa, U., Miyake, R., Tanaka, Y., Takai, Y. & Nishizuka, Y. Cold Spring Harb. Conf. Cell Proliferation 11, (in the press).
56.	Fujiki, H. et al. in Cellular Interactions by Environmental Tumor Promoters (ed. Sugimura, T.) (Japan Sci. Soc., Tokyo, in the press).
57.	Swilen, A. M. F., Hawthorne, J. N. & Azia, N. Biochem, Pharmac. 32 (in the press).
58.	Kajikawa, N. et al. Biochem. biophys. Res. Commun. 116, 743−750 (1983). | PubMed | ISI | ChemPort |
59.	Witz, G., Goldstein, B. D., Amoruso, M., Stone, D. S. & Troll, W. Biochem. biophys. Res. Commun. 97, 883−888 (1980). | PubMed | ISI | ChemPort |
60.	Rink, T. J., Sanchez, A. & Hallam, T. J. Nature 305, 317−319 (1983). | Article | PubMed | ISI | ChemPort |
61.	Knight, D. E., Hallam, T. J. & Scrutton, M. C. Nature 296, 256−257 (1982). | PubMed | ISI | ChemPort |
62.	Kaibuchi, K., Sawamura, M., Kikkawa, U., Takai, Y. & Nishizuka, Y. in Inositol and Phosphoinositides (eds Bleasdale, J. E., Eichberg, J. & Hauser, J.) (Humana, Dallas, in the press).
63.	Knight, D. E. & Baker, P. F. FEBS Lett. 160, 98−100 (1983). | Article | PubMed | ISI | ChemPort |
64.	Kojima, I., Lippes, H., Kojima, K. & Rasmussen, H. Biochem. biophys. Res. Commun. 116, 555−562 (1983). | PubMed | ISI | ChemPort |
65.	Zawalich, W., Brown, C. & Rasmussen, H. Biochem. biophys. Res. Commun. 117, 448−455 (1983). | PubMed | ISI | ChemPort |
66.	Garrison, J. C., Johnsen, D. E. & Campanile, C. P. J. biol. Chem. (in the press).
67.	Fain, J. N., Li, S.-Y., Litosch, I. & Wallace, M. Biochem. biophys. Res. Commun. (in the press).
68.	Mastro, A. M. & Smith, M. C. J. cell. Physiol. 116, 51−56 (1983). | PubMed | ISI | ChemPort |
69.	Werth, D. K., Niedel, J. E. & Pastan, I. J. biol Chem. 258, 11423−11426 (1983). | PubMed | ChemPort |
70.	Le Peuch, C. J., Ballester, R. & Rosen, O. M. Proc. natn. Acad. Sci. U.S.A. 80, 6858−6862 (1983). | ChemPort |
71.	Naka, M., Nishikawa, M., Adelstein, R. S. & Hidaka, H. Nature 306, 490−492 (1983). | Article | PubMed | ISI | ChemPort |
72.	Schatzman, R. C., Grifo, J. A., Merrick, W. C. & Kuo, J. F. FEBS Lett. 159, 167−170 (1983). | Article | PubMed | ISI | ChemPort |
73.	Martin, G. S. & Gilmore, T. Nature 306, 487−490 (1983). | Article | PubMed | ISI |
74.	Streb, H., Irvine, R. F., Berridge, M. J. & Schulz, I. Nature 306, 67−69 (1983). | Article | PubMed | ISI | ChemPort |
75.	Bell, R. L., Kennerley, D. A., Stanford, N. & Majerus, P. W. Proc. natn. Acad. Sci. U.S.A. 76, 3238−3241 (1979). | ChemPort |
76.	Billah, M. M., Lapetina, E. G. & Cuatrecasas, P. J. biol. Chem. 256, 5399−5403 (1981). | PubMed | ISI | ChemPort |
77.	Graff, G., Stephenson, J. H., Glass, D. B., Haddox, M. K. & Goldberg, N. D. J. biol. Chem. 253, 7662−7676 (1978). | PubMed | ISI | ChemPort |
78.	Takai, Y., Kaibuchi, K., Matsubara, T. & Nishizuka, Y. Biochem. biophys. Res. Commun. 101, 61−67 (1981). | PubMed | ISI | ChemPort |
79.	Haslam, R. J., Salama, S. E., Fox, J. E. B., Lynham, J. A. & Davidson, M. M. L. in Platelets: Cellular Response Mechanisms and their Biological Significance (eds Rotman, A., Meyer, F. A., Gitler, C. & Silderberg, A.) 213−231 (Wiley, New York, 1980). | ChemPort |
80.	Schultz, K. D., Schultz, K. & Schultz, G. Nature 265, 750−751 (1977). | PubMed | ISI | ChemPort |