Summary
Cyclic AMP-dependent protein kinase has been well established to be composed of catalytic and regulatory subunits, and cyclic AMP acts to dissociate these subunits to exhibit full enzymatic activity. In contrast, cyclic GMP-dependent protein kinase does not possess such a subunit structure and is activated by cyclic GMP simply in an allosteric manner. In addition to cyclic AMP-dependent and cyclic GMP-dependent protein kinases, another species of multifunctional protein kinase has been found in many mammalian tissues. This protein kinase is entirely independent of cyclic nucleotides and activated by lower concentrations of Ca21 in the presence of a membrane-associated factor. This factor has been identified as phospholipids; in fact, phosphatidylinositol and phosphatidylserine are active in this role, whereas lecithin and sphingomyelin are unable to activate the enzyme. Thus, the three species of protein kinases mentioned above are activated in different manners. Nevertheless, these enzymes show very similar substrate specificities and phosphorylate the same specific seryl residues of histone fractions. In addition, all enzymes have abilities to activate and inactivate muscle phosphorylase kinase and glycogen synthetase, respectively, although the relative rates of reactions towards various substrates are markedly different. The Ca2+-dependent protein kinase seems to be associated with membranous components, whereas cyclic GMP-dependent protein kinase appears to be related to certain subcellular organella such as nucleus. Suggestive evidence is available implying that the cyclic AMP-, cyclic GMP- and Ca2+-activated three sets of protein kinase systems may play each specific physiological roles presumably owing to their own subcellular compartments.
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Abbreviations
- cyclic AMP:
-
adenosine 3′, 5′-monophosphate
- cyclic GMP:
-
guanosine 3′,5′-monophosphate
- EGTA:
-
ethylene glycol bis(β-amino-ethylether)-N,N,N′,N′-tetraacetic acid
References
Walsh, D. A., Perkins, J. P. and Krebs, E. G., 1968. J. Biol. Chem. 243, 3763–3765.
Sherline, P., Lynch, A. and Glinsmann, W. H., 1972. Endocrinology 91, 680–690.
Kirk, C. J. and Hems, D. A., 1974. FEBS Letters 47, 128–131.
Keppens, S. and De Wulf, H., 1975. FEBS Letters 51, 29–32.
Keppens, S. and De Wulf, H., 1976. FEBS Letters 68, 279–282.
Kishimoto, A., Takai, Y. and Nishizuka, Y., 1977. J. Bio. Chem. 252, 7449–7452.
Takai, Y., Kishimoto, A., Inoue, M. and Nishizuka, Y., 1977. J. Biol. Chem. 252, 7603–7609.
Inoue, M., Kishimoto, A., Takai, Y. and Nishizuka, Y., 1977. J. Biol. Chem. 252, 7610–7616.
Takai, Y., Yamamoto, M., Inoue, M., Kishimoto, A. and Nishizuka Y., 1977. Biochem. Biophys. Res. Commun. 77, 542–550.
Kishimoto, A., Mori, T., Takai, Y. and Nishizuka, Y., 1978. J. Biochem. 84, 47–53.
Yamamoto, M., Takai, Y., Inoue, M., Kishimoto, A. and Nishizuka, Y., 1978. J. Biochem. 83, 207–212.
Nishizuka, Y., Takai, Y., Kishimoto, A., Hashimoto, E., Inoue, M., Yamamoto, M., Criss, W. E. and Kuroda, Y., 1978. Advances in Cyclic Nucleotide Research 9, 209–220.
Kuo, J. F. and Greengard, P., 1970. J. Biol. Chem. 245,2493–2498.
Hofmann, F. and Sold, G., 1972. Biochem. Biophys. Res. Commun. 49, 1100–1107.
Van Leemput-Coutrez, M., Camus, J. and Christophe, J., 1973. Biochem. Biophys. Res. Commun. 54, 182–190.
Kuo, J. F., 1974. Proc. Natl. Acad. Sci. U.S. 71, 4037–4041.
Shima, S., Mitsunaga, M., Kawashima, Y., Taguchi, S., and Nakao, T., 1974. Biochim. Biophys. Acta 341, 56–64.
Takai, Y., Nishiyama, K., Yamamura, H. and Nishizuka, Y., 1975. J. Biol. Chem. 250, 4690–4695.
Nakazawa, K. and Sano, M., 1975. J. Biol. Chem. 250, 7415–7419.
Kuo, J. F., Kuo, W. N., Shoji, M., Davis, C. W., Seery, V. L. and Donnelly, T. E., 1976. J. Biol. Chem. 251,1759–1766.
Gill, G. N., Holdy, K. E., Walton, G. M. and Kanstein, C. B., 1976. Proc. Natl. Acad. Sci. U.S. 73, 3918–3922.
Lincoln, T. M. and Corbin, J. D., 1977. Proc. Natl. Acad. Sci. U.S. 74, 3239–3243.
De Jonge, H. R. and Rosen, O. M., 1977. J. Biol. Chem. 252, 2780–2783.
Flockerzi, V., Speichermann, N. and Hofmann, F., 1978. J. Biol. Chem. 253, 3395–3399.
Takai, Y., Nakaya, S., Inoue, M., Kishimoto, A., Nishiyama, K., Yamamura, H. and Nishizuka, Y., 1976. J. Biol. Chem. 251, 1481–1487.
Lincoln, T. M., Dills, W. L. and Corbin, J. D., 1977. J. Biol. Chem. 252, 4269–4275.
Langan, T. A., 1973, Advances in Cyclic Nucleotide Research 3, 99–153.
Rubin, C. S. and Rosen, O. M., 1975. Ann. Rev. Biochem. 44, 831–887.
Nimmo, H. G. and Cohen, P., 1977. Advances in Cyclic Nucleotide Research 8, 145–266.
Lincoln, T. M. and Corbin, J. D., 1978. J. Cyclic Nucleot. Res. 4, 3–14.
Kuo, J. F., Shoji, M. and Kuo, W. N., 1978. Ann. Rev. Pharmacol. Toxicol. 18, 341–355.
Kuo, J. F. and Greengard, P., 1969. Proc. Natl. Acad. Sci. U.S. 64, 1349–1355.
Yamamura, H., Takeda, M., Kumon, A. and Nishizuka, Y., 1970. Biochem. Biophys. Res. Commun. 40, 675–682.
Tao, M., Salas, M. and Lipmann, F., 1970. Proc. Natl. Acad. Sci. U.S. 67, 408–414.
Reimann, E. M., Walsh, D. A. and Krebs, E. G., 1971. J. Biol. Chem. 246, 1986–1995.
Gill, G. N. and Garren, L. D., 1971. Proc. Natl. Acad. Sci. U.S. 68, 786–790.
Erlichman, J., Hirsch, A. H. and Rosen, O. M., 1971. Proc. Natl. Acad. Sci. U.S. 68, 731–735.
Kumon, A., Yamamura, H. and Nishizuka, Y., 1970. Biochem. Biophys. Res. Commun. 41, 1290–1297.
Kumon, A., Nishiyama, K., Yamamura, H. and Nishizuka, Y., 1972. J. Biol. Chem. 247, 3726–3735.
Chen, L. J. and Walsh, D. A., 1971. Biochemistry 10, 3614–3621.
Corbin, J. D., Brostrom, C. O., King, C. A. and Krebs, E. G., 1972. J. Biol. Chem. 247, 7790–7798.
Tao, M. and Hackett, P., 1973. J. Biol. Chem. 248, 5324–5332.
Yamamura, H., Kumon, A. and Nishizuka, Y., 1971. J. Biol. Chem. 246, 1544–1547.
Yamamura, H., Nishiyama, K., Shimomura, R. and Nishizuka, Y., 1973. Biochemistry 12, 856–862.
Takai, Y., Yamamura, H. and Nishizuka, Y., 1974. J. Biol. Chem. 249, 530–535.
Fleischer, N., Rosen, O. M. and Reichlin, M., 1976. Proc. Natl. Acad. Sci. U.S. 73, 54–58.
Kuo, J. F., Wyatt, G. R. and Greengard, P., 1971. J. Biol. Chem. 246, 7159–7167.
Takahashi, S. Y., Kageyama, T., Ohoka, T. and Ohnishi, E., 1974. Insect Biochem. 4, 429–434.
Nishiyama, K., Katakami, H., Yamamura, H., Takai, Y., Shimomura, R. and Nishizuka, Y., 1975. J. Biol. Chem. 250, 1297–1300.
Miyamoto, E., Petzold, G. L., Kuo, J. F. and Greengard, P., 1973. J. Biol. Chem. 248, 179–189.
Shoji, M., Patrick, J. G., Tse, J. and Kuo, J. F., 1977. J. Biol. Chem. 252, 4347–4353.
Kuo, J. F., Patrick, J. G. and Seery, V. L., 1976. Biochem. Biophys. Res. Commun. 72, 996–1002.
Kobayashi, R. and Fang, V. S., 1976. Biochem. Biophys. Res. Commun. 69, 1080–1087.
Castagna, M. and Rochette, C., 1978. Advances in Cyclic Nucleotide Research 9, 749–750.
Nishizuka, Y., Takai, Y., Hashimoto, E., Kishimoto, A., Inoue, M. and Takeda, M., 1976. Control Mechanisms in Cancer (W. E. Criss, T. Ono and J. R. Sabine, ed.) pp. 139–152, Raven Press, New York.
Nishizuka, Y., 1976. J. Biochem. 79, 42p.
Inoue, M., Kishimoto, A., Takai, Y. and Nishizuka, Y., 1976. J. Biol. Chem. 251, 4476–4478.
Lincoln, T. M., Flockhart, D. A. and Corbin, J. D., 1978. J. Biol. Chem. 253, 6002–6009
Gill, G. N., Walton, G. M. and Sperry, P. J., 1977. J. Biol. Chem. 252, 6443–6449.
Yamamura, H., Inoue, Y., Shimomura, R. and Nishizuka, Y. 1972. Biochem. Biophys. Res. Commun. 46, 589–596.
Takai, Y., Sakai, K., Morishita, Y., Yamamura, H. and Nishizuka, Y., 1974. Biochem. Biophys. Res. Commun. 59, 646–652.
Dabrowska, R., Sherry, J. M. F., Aromatorio, D. K. and Hartshorne, D. J., 1978. Biochemistry 17, 253–258.
Yagi, K., Yazawa, M., Kakiuchi, S., Ohsima, M. and Uenishi, K., 1978. J. Biol. Chem. 253, 1338–1340.
Cheung, W. Y., 1970. Biochem. Biophys. Res. Commun. 38, 533–538.
Kakiuchi, S. and Yamazaki, R., 1970. Biochem. Biophys. Res. Commun. 41, 1104–1110.
Perrie, W. T., Smillie, L. B. and Perry, S. V., 1973. Biochem. J. 135, 151–164.
Waisman, D. M., Singh, T. J. and Wang, J. H., 1978. J. Biol. Chem. 253, 3387–3390.
Huang, L. C. and Huang, C., 1975. Biochemistry 14, 18–24.
Langan, T. A., 1968. Science 162, 579–581.
Friedman, D. L. and Larner, J., 1963. Biochemistry 2, 669–675.
Schlender, K. K., Wei, S. H. and Villar-Palasi, C., 1969. Biochim. Biophys. Acta 191, 272–278.
Soderling, T. R., Hickenbottom, J. P., Reimann, E. M., Hunkeler, F. L., Walsh, D. A. and Krebs, E. G., 1970. J. Biol. Chem. 245, 6317–6328.
Hjelmquist, G., Andersson, J., Edlund, B. and Engström, L., 1974. Biochem. Biophys. Res. Commun. 61, 559–563.
Huang, T. S., Bylund, D. B., Stull, J. T. and Krebs, E. G., 1974. FEBS Letters 42, 249–252.
Moir, A. J. G., Wilkinson, J. M. and Perry, S. V., 1974. FEBS Letters 42, 253–256.
Carnegie, P. R., Dunkley, P. R., Kemp, B. E. and Murray, A. W., 1974. Nature 249, 147–150.
Cohen, P., Watson, D. C. and Dixon, G. H., 1975. Eur. J. Biochem. 51, 79–92.
Kemp, B. E., Bylund, D. B., Huang, T. S. and Krebs, E. G., 1975. Proc. Natl. Acad. Sci. U.S. 72, 3448–3452.
Hashimoto, E., Takeda, M., Nishizuka, Y., Hamana, K. and Iwai, K., 1975. Biochem. Biophys. Res. Commun. 66, 547–555.
Edlund, B., Andersson, J., Titanji, V., Dahlqvist, U., Ekman, P., Zetterqvist, O. and Engström, L., 1975. Biochem. Biophys. Res. Commun. 67, 1516–1521.
Bylund, D. B. and Krebs, E. G., 1975. J. Biol. Chem. 250, 6355–6361.
Yeaman, S. J., Cohen, P., Watson, D. C. and Dixon, G. H., 1976. Biochem. Soc. Trans. 4, 1027–1030.
Kuroda, Y., Hashimoto, E., Nishizuka, Y., Hamana, K. and Iwai, K., 1976. Biochem. Biophys. Res. Commun. 71, 629–635.
Hashimoto, E., Takeda, M., Nishizuka, Y., Hamana, K. and Iwai, K., 1976. J. Biol. Chem. 251, 6287–6293.
Yamamoto, M., Takai, Y., Hashimoto, E. and Nishizuka, Y., 1977. J. Biochem. 81, 1857–1862.
Chihara-Nakashima, M., Hashimoto, E. and Nishizuka, Y., 1977. J. Biochem. 81, 1863–1867.
Khoo, J. C., Sperry, P. J., Gill, G. N. and Steinberg, D., 1977. Proc. Nati. Acad. Sci. U.S. 74, 4843–4847.
Blumenthal, D. K., Stull, J. T. and Gill, G. N., 1978. J. Biol. Chem. 253, 334–336.
Lincoln, T. M. and Corbin, J. D., 1978. J. Biol. Chem. 253,337–339.
Casnellie, J. E. and Greengard, P., 1974. Proc. Natl. Acad. Sci. U.S. 71, 1891–1895.
91.Wallach, D., Davies, P. J. A. and Pastan, I., 1978. J. Biol. Chem. 253, 4739–4745.
De Jonge, H. R., 1976. Nature 262, 590–593.
93.Schlichter, D. J., Casnellie, J. E. and Greengard, P., 1978. Nature 273, 61–62.
Cohen, P., 1973. Eur. J. Biochem. 34, 1–14.
Hayakawa, T., Perkins, J. P. and Krebs, E. G., 1973. Biochemistry 12, 574–580.
Walsh, D. A., Ashby, C. D., Gonzalez, C., Calkins, D., Fischer, E. H. and Krebs, E. G., 1971. J. Biol. Chem. 246, 1977–1985.
Ashby, C. D. and Walsh, D. A., 1972. J. Biol. Chem. 247,6637–6642.
Ashby, C. D. and Walsh, D. A., 1973. J. Biol. Chem. 248, 1255–1261.
Donnelly, T. E., Kuo, J. F., Reyes, P. L., Liu, Y. P. and Greengard, P., 1973. J. Biol. Chem. 248, 190–198.
Donnelly, T. E., Kuo, J. F., Miyamoto, E. and Greengard, P. 1973. J. Biol. Chem. 248, 199–203.
Kuo, W. N., Shoji, M. and Kuo, J. F., 1976. Biochim. Biophys. Acta 437, 142–149.
Kuo, W. N., Shoji, M. and Kuo, J. F., 1976. Biochem, Biophys. Res. Commun. 70, 280–286.
Kuo, W. N. and Kuo, J. F., 1977. J. Biol. Chem. 251, 4283–4286.
Shoji, M., Brackett, N. L., Tse, J., Shapira, R. and Kuo, J. F., 1978. J. Biol. Chem. 253, 3427–3434.
Kornberg, R. D., 1977. Ann. Rev. Biochem. 46, 931–954.
Steiner, A. L., Ong, S. and Wedner, H. J., 1976. Advances in Cyclic Nucleotide Research, 7, 115–155.
Steiner, A. L., Koide, Y., Earp, H. S., Bechtel, P. J. and Beavo, J. A. 1978. Advances in Cyclic Nucleotide Research, 9, 691–705.
Taniyama, K., Yoshida, N. and Tanaka, C., 1978. Japan J. Pharmacol. 38 supplement, in press.
Maeno, H., Johnson, E. M. and Greengard, P., 1971. J. Biol. Chem. 246, 134–142.
Goldberg, N. D. and Haddox, M. K., 1977. Ann. Rev. Biochem. 46, 823–896.
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Nishizuka, Y., Takai, Y., Hashimoto, E. et al. Regulatory and functional compartment of three multifunctional protein kinase systems. Mol Cell Biochem 23, 153–165 (1979). https://doi.org/10.1007/BF00219454
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DOI: https://doi.org/10.1007/BF00219454