Phosphorylase Kinase and Protein Kinase C: Functional Similarities

  • T. G. Sotiroudis
  • S. M. Kyriakidis
  • L. G. Baltas
  • T. B. Ktenas
  • V. G. Zevgolis
  • A. E. Evangelopoulos
Conference paper
Part of the NATO ASI Series book series (volume 29)


Protein serine and threonine Kinases can be classified into individual groups or subclasses on the basis of the type of regulation of their activities (Krebs, 1986). Two of the most intensively studied groups are Ca2+-regulated, i.e. the Ca2+/calmodulin (CaM)-dependent and the Ca2+-phospholipid (diacylglycerol)-dependent protein Kinases. Of the enzymes belonging in the category of Ca2+/ CaM-dependent Kinases, myosin light chain Kinases (MLCK) are distinguished by their high degree of substrate specificity and CaM dependency (Edelman et al, 1987). Fhosphorylase Kinase (FhK) another member of the same group is characterized by a broader substrate specificity. Its primary substrate is phosphorylase b but the enzyme may catalyze the phosphorylation of other proteins (Chan & Graves, 1984). In addition, a number of Ca2+/CaM-dependent multifunctional protein Kinases identified in a variety of tissues shows a broad substrate specificity suggesting that such a group of CaM-dependent protein Kinases may play inportant roles in the control of different cellular processes (Sienolikar etal, 1986). On the other hand, protein Kinase C (PKC) is a multifunctional protein Kinase identified by Nishizuka and co-worKers as a Ca2+- and phospholipid-dependent protein Kinase that plays a crucial role in the signal transduction for a variety of biologically active substances involved in cellular function and proliferation (Nishizuka, 1984).


Phorbol Ester Myosin Light Chain Kinase Glycogen PhosPhorylase Dependent Protein Kinase Broad Substrate Specificity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Albert, K. A., Wu, W.C-S, Nairn, A.C. and Greengard, P. (1984) Inhibition of calcium/phospholipid-dependent. protein phosphorylation. Proc. Natl. Acad. Sci. USA 81, 3622–3625PubMedCrossRefGoogle Scholar
  2. Baltas, L. G., Zevgolis, V. G., Kyriakidis, S. M., Sotiroudis, T. G. and Evangelopoulos, A. E. in preparationGoogle Scholar
  3. Bazzi, M. D. and Nelsestuen, G. L. (1988) Constitutive activity of membrane-inserted protein Kinase C. Biochem. Biophys. Res. Conraan, 152, 336–343CrossRefGoogle Scholar
  4. Burn, P. (1988) Arrphi tropic proteins: A new class of membrane proteins. Trends Biochem. Sci., 13, 79–83PubMedCrossRefGoogle Scholar
  5. Castagna, H., Pavone, C., Bazgar, S., Couturier, A., Chevalier, M. and Fiszman, M. (1985) Phospholipid/Ca2+-dependent protein Kinase, cell differentiation and tumor promotion. In: Hormones and Cell Regulation (Dumont,J.E. etal, eds) Vol.9, 185–206, Elsevier Science Publishers BVGoogle Scholar
  6. Chan, K.-F. J. & Graves, D. J. (1984) Molecular properties of Phosphorylase Kinase. In: Calcium & Cell Function (Cheung,W.Y.,ed) Vol.5, 1–31, Academic Press, New YorkGoogle Scholar
  7. Chauhan, V. P. S. and Brockerhoff, H. (1988) Phosphatidylinositol,-4-5 biphosphate antecede diacylglycerol as activator of protein Kinase C. FASEB J. 2, A349Google Scholar
  8. Cox, J. A. (1988) Interactive properties of calmodulin. Biochem. J. 249, 621–629Google Scholar
  9. Dombradi, V. K., Silberman, S.R., Lee, E. Y. C., Caswell, A. H. & Brandt, N. R. (1984) The association of Phosphorylase Kinase with rabbit muscle T-tubules. Arch. Biochem. Biophys. 230, 615–630PubMedCrossRefGoogle Scholar
  10. Edelman, A. M., Blumenthal, D. K. and Krebs, E.G. (1987) Protein serine-threonine Kinases. Ann. Rev. Biochem. 56, 567–613Google Scholar
  11. Fujiki, H., Yamashita, K., Suganuma, M., Horiuchi, T., Taniguchi, N. and Makita, A. (1986) Involvement of sulfatide in activation of protein Kinase C by tumor promoters Biochem. Biophys, Res. Corrmun, 138, 153–158CrossRefGoogle Scholar
  12. Gietzen, K., Sadorf, I. and Bader, H. (1981) A model for the regulation of the calmodul independent enzymes erythrocyte Ca2+-transport ATPase and brain phosphodiesterase by activators and inhibitors. Biochem. J. 207, 541–548Google Scholar
  13. Gschwendt, M., Horn. F., Kittstein,W. and Marks, F. (1983) Inhibition of the calcium- and phospholipid-dependent protein Kinase activity from mouse brain cytosol by quercetin. Biochem. Biophys. Res. Coramin. 117, 444–447Google Scholar
  14. Hanley, R. M., Means, A. R., Kemp, B. E. and Shenolikar, S. (1988) Mapping of calmodulin-binding domain of Ca2+/calmodul in-dependent protein Kinase II frem rat brain. Biochem, Biophys.Res.Commun. 152, 122–128CrossRefGoogle Scholar
  15. Hannun, Y. A., Loomis, C. R. Merrill, A. H. Jr and Bell, R. M. (1986) Sphingosine inhibition of protein Kinase C activity and of phorbol dibutyrate binding in vitro and in human platelets. J.Biol.Chem. 261, 12604–12609Google Scholar
  16. Hannun, Y. A. and Bell, R. M. (1987) Lysosphingolipids inhibit protein Kinase C: Implications for the sphingolipidoses. Science, 235, 670–674Google Scholar
  17. Hansson, A., Skoglund, G., Lassing, I., Lindberg, U. and Ingelman-Sundberg, M. (1988) Protein Kinase C-dependent phosphorylation of profilin is specifically stimulated by phosphatidylinositol biphosphate (PIP2). Biochem. Biophys. Res. Cormun. 150, 526–531Google Scholar
  18. Hessova, Z., Varsanyi, M. & Heilmeyer, L. M. G., Jr. (1985) Dual function of calmodulin (δ) in Phosphorylase Kinase. Eur. J.Biochem. 146, 107–115PubMedCrossRefGoogle Scholar
  19. Hörl, W. H., Jennissen, H. B. and Heilmeyer, L. M. G.,Jr. (1978) Evidence for the participation of a Ca2+-dependend protein Kinase and a protein phosphatase in the regulation of the Ca2+-transport ATPase of the sarcoplasmic reticulum 1. Effect of inhibitors of the Ca2+-dependent protein Kinase and protein phosphatase. Biochemistry IT, 759–766Google Scholar
  20. Ito, M., Tanaka, T., Inagaki, M., Nakanishi, K. and Hidaka, H. (1986) N- (6-Phenylhexy 1) -5-chloro-1 -Naphtha 1 enesul f onamide. A nove 1 activator of protein Kinase C. Biochemistry 25, 4179–4184PubMedCrossRefGoogle Scholar
  21. Juskevich, J.C. Kuhn, D. M. and Lovenberg, W. (1983) Phosphorylation of brain cytosol proteins. Effects of phospholipids and calmodulin. J.Biol. Chem. 258, 1950–1953Google Scholar
  22. Kikkawa, V. and Nishizuka, Y. (1986) Protein Kinase C. In: The Enzymes ( Boyer,P and Krebs,E.G. eds) Vol. 17, 167–189, Academic Press, New York.Google Scholar
  23. Kishimoto, A., Kajikawa, N., Siota, M. and Nishizuka, Y. (1983) Proteolytic activation of calmodulin-activated, phospholipid-dependent protein Kinase by calcium-dependent neutral protease. J.Biol.Chem. 258, 1156–1164PubMedGoogle Scholar
  24. Kraft, A. S. and Anderson,W. B. (1983) Fhorbol esters increase the amount of Ca2+, phospholipid-dependent protein Kinase associated with plasma membrane. Nature (London) 301, 621–623CrossRefGoogle Scholar
  25. Krebs, E. G. (1986) The enzymology of control by phosphorylation, in: The Enzymes (Boyer,P. and Krebs,E.G. eds) Vol.17, 3–20, Academic Press New YorkGoogle Scholar
  26. Kreutter, D., Kim, J. Y. H., Goldenring, J. R., Rasmussen, H. UKomadu, C., DeLorenzo, R. J, and Yu, R. K. (1987) Regulation of protein Kinase C activity by gangliosides. J.Biol.Chem 262, 1633–1637Google Scholar
  27. Ktenas, T. B., Sotiroudis,T. G., NiKolaropoulos, S. and Evangelopoulos, A. E. (1985) Interaction of Phosphorylase Kinase with polymixins Biochem. Biophys. Res. Commun. 133, 891–896Google Scholar
  28. Ktenas, T. B., Sotiroudis, T. G. and Evangelopoulos, A. E. in preparationGoogle Scholar
  29. Kyriakidis, S. M., Sotiroudis, T. G. & Evangelopoulos, A. E. (1986a) Stimulation of glycogen Phosphorylase Kinase with phospholipids. Biochem Inter. 13, 853–861Google Scholar
  30. Kyriakidis, S. M., Sotiroudis, T. G. & Evangelopoulos, A. E. (1986b) Interaction of flavonoids with rabbit muscle Phosphorylase Kinase. Biochim. Biophys. Acta 871, 121–129Google Scholar
  31. Kyriakidis, S. M., Sotiroudis, T. G. and Evangel opoulos, A. E, (1988) Ca2+ and Mg2+- dependent association of Phosphorylase Kinase with human erythrocyte membranes. Submitted for publicationGoogle Scholar
  32. Lucas, T. J., Burgess, W.H., Prendergast, F. G., Lau, W. and Watterson, D. M. (1986) Calmodulin binding domains: Characterization of a phosphorylating and calmodulin binding site from myosin light chain Kinase. Biochemistry, 25, 1458–1464CrossRefGoogle Scholar
  33. Mamoi, T. (1986) Activation of protein Kinase C by ganglioside GM3 in the presence of calcium and 12-o-tetradecanoylphorbol-13-acetate Biochem. Biophys. Res. Commun. 138, 865–871Google Scholar
  34. Mazzei, G.J., Qi, D. -F., Schatzman, R. C., Raynor, R. L., Turner, R. S. and Kuo, J. F. (1983) Conparative abilities of lanthanide ions La3+ and Tb3+ to substitute for Ca2+ in regulating phospholipid-sensitive Ca2+-dependent Kinase and myosin light chain Kinase. Life Sci. 33, 119–129PubMedCrossRefGoogle Scholar
  35. Mazzei,G.J., Girrard.P. and Kuo, J.F. (1984) Environmental pollutant Cd2+ biphasically and differentially regulates myosin light chain Kinase and phospholipid/Ca2+-dependent protein Kinase FEBS Lett. 173, 124–128Google Scholar
  36. Meyer, T., Fabro, D., Eppenberger, U. and Matter, A. (1986) The lipophilic muramyltripeptide MIP-PE, a biological response modifier, is an activator of protein Kinase C. Biochem Biophys. Res. Comuun. 140, 1043–1050CrossRefGoogle Scholar
  37. Murakami, K., Chan, S. Y. and Routtenberg, A. (1986) Protein Kinase C activation by cis-fatty acid in the absence of Ca2+ and phospholipids. J.Biol.Chem. 261, 15424–15429PubMedGoogle Scholar
  38. Murakami, K., Whitley, M. K. and Routtenberg, A. (1987) Regulation of protein Kinase C activity by cooperative interaction of Zn2+ and Ca2+. J.Biol.Qiem. 262, 13902–13906Google Scholar
  39. Negami, A. I., Sasaki, H. and Yamamura, H. (1986) Activation of phosphorylase Kinase through autophosphorylation by membrane component phospholipids. Eur.J.Biochem. 157, 597–603PubMedCrossRefGoogle Scholar
  40. Nikolaropoulos, S. and Sotiroudis, T. G. (1985) Phosphorylase Kinase from chicken gizzard. Partial purification and characterization, Eur. J. Biochem. 151, 467–473Google Scholar
  41. Nishizuka.Y, (1984) The role of protein Kinase C in cell-surface signal transduction and tumor promotion. Nature 308, 693–698Google Scholar
  42. Nishizuka.Y. (1986) Studies and perspectives of protein Kinase C. Science 233, 305–312Google Scholar
  43. ParKer, P. J. and Ullrich, A. (1987) Protein Kinase C. J.Cell.Physiol.Suppl. 553–56Google Scholar
  44. PicKett-Giese, C. A. & Walsh, D. A. (1986) Phosphorylase Kinase. In: The Enzymes (Boyer.P. & Krebs,E.G.,eds) Vol.17, 395–459, Academic Press, New YorkGoogle Scholar
  45. Sakai, K., Kobayashi, T., Komuvo, T., Nakamura, S., Mizuta, K., Sakanoue, Y., Hashimoto, E. and Yamanura, H. (1987) Non-requirement of calcium on protamine phosphorylation by calcium-activated, phospholipid dependent protein Kinase. Biochem. Inter. 14, 63–70Google Scholar
  46. Shenolikar, S., Cohen, P. T.W., Cohen, P., Nairn, A.C. and Perry, S. V. (1979) Role of calmodulin in the structure and regulation of phosphosphorylase Kinase from rabbit sKeletal muscle. Eur. J. Biochem. 100, 329–337PubMedCrossRefGoogle Scholar
  47. Shenolikar, S., Lickteig, R., Hardie, D.G., Soderling.T.R., Hanley, R.M. and Kelly, P.T. (1986) Calmodulin-dependent multifunctional protein Kinases. Evidence for isoenzyme forms in maiunalian tissues Eur. J. Biochem. 161, 739–747Google Scholar
  48. Singh, T. J. & Wang, J. H. (1979) Stimulation of glycogen Phosphorylase Kinase from rabbit skeletal muscle by organic solvents. J. Biol.Chem. 254, 8466–8472PubMedGoogle Scholar
  49. Sotiroudis, T. G. (1986) Lanthanide ions and Cd2+ are able to substitute for Ca2+ in regulating Phosphorylase Kinase. Biochem. Inter. 13, 59–64Google Scholar
  50. Stull, J. T., Nunnally, M. H. and Michnoff, C. H. (1986) Calmodul in-dependent protein Kinases. In: Ihe Enzymes (Boyer,P. and Krebs,E.G.,eds) vol. 17, 113–166, Academic Press, New YorkGoogle Scholar
  51. Takai, Y., Kishimoto, A., Iwasa.Y., Kawahara, Y., Mori, T. and Nishizuka, Y. (1979) Calcium-dependent activation of a multifunctional protein Kinase by membrane phospholipids, J.Biol.Chem. 254, 3692–3695Google Scholar
  52. Thieleczek, R., Behle, G., Messer, A., Varsanyi, M., Heilmeyer, L. M. G., Jr. & Drenckhahn,D. (1987) Localization of Phosphorylase Kinase subunits at the sarcoplasmic reticulum of rabbit sKeletal muscle by monoclonal and polyclonal antibodies. Eur. J.Cell Biol. 44, 333–340Google Scholar
  53. Wightman, P. D. and Raetz, C. R. H. (1984) The activation of protein Kinase C by biologically active lipid moi et es of lipopolysaccharide. J. Biol. Chem. 259, 10048–10052PubMedGoogle Scholar
  54. Wolf, M., LeVine III, H., May, S., Jr, Cuatrecasas, P. and Sahyoun, N. (1985) A model for intracellular translocation of protein Kinase C involving synergism between Ca2+ and phorbolesters. Nature 317, 546–549PubMedCrossRefGoogle Scholar
  55. Zevgolis, V. G., Sotiroudis, T. G. and Evangelopoulos, A. E. in preparationGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • T. G. Sotiroudis
    • 1
  • S. M. Kyriakidis
    • 1
  • L. G. Baltas
    • 1
  • T. B. Ktenas
    • 1
  • V. G. Zevgolis
    • 1
  • A. E. Evangelopoulos
    • 1
  1. 1.The National Hellenic Research FoundationAthensGreece

Personalised recommendations