Effect of Polyamines on Protein Kinase C Activation Process

  • Maria Stella Moruzzi
  • Giorgio Piccinini
  • Bruna Tadolini
  • Maria Giuseppina Monti
  • Bruno Barbiroli
  • Gabriele Mezzetti
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 250)


Protein phosphorylation and dephosphorylation are major mechanisms for signal transduction in biological systems (Krebs, 1985) and are fundamental in the regulation of many cellular activities (Rubin and Rosen, 1975). The Ca2+ and phospholipid-dependent protein kinase C (PKC) is a key regulatory enzyme believed to be involved in basic cell functions such as proliferation and differentiation (Schwantke et al., 1985). Activation of PKC by diacylglycerol (DAG) has linked the activity of this enzyme to the function of many stimuli acting via phosphatidylinositol turnover (Berridge, 1987). Indeed DAG has been postulated to be the second messenger able to activate PKC without a change in cytosolic Ca2+ concentration. Biologically active phorbol esters which usually act as tumor promoters also activate PKC and are presumed to exert their functions in this way; indeed this enzyme appears to be a cellular phorbol ester receptor (Ashendel, 1985).


Phorbol Ester Phospholipid Vesicle Acidic Phospholipid PDBu Binding Phorbol Dibutyrate 
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. Ashendel, C.L., 1985, The phorbol ester receptor: a phospholipidregulated protein kinase, Biochim. Biophys. Acta, 822: 219.PubMedGoogle Scholar
  2. Bazzi, M.D., and Nelsestuen, G.L., 1987, Association of protein kinase C with phospholipid vesicles, Biochemistry, 26: 115.PubMedCrossRefGoogle Scholar
  3. Bell, R.M., 1986, Protein kinase C activation by diacylglycerol second messengers, Cell, 45: 631.PubMedCrossRefGoogle Scholar
  4. Berridge, M.J., 1987, Inositol trisphosphate and diacylglycerol: two interacting second messengers, Ann. Rev. Biochem., 56: 159.PubMedCrossRefGoogle Scholar
  5. Chung, L., Kaloyanides, G., McDaniel, R., McLaughlin, A., and McLaughlin, S., 1985, Interaction of gentamicin and spermine with bilayer membranes containing negatively charged phospholipids, Biochemistry 24: 442.PubMedCrossRefGoogle Scholar
  6. Gazzotti, P., and Peterson, S.W., 1977, Lipid requirement of membrane—bound enzymes, J. Bioenerg. Biomemb. 9: 373.CrossRefGoogle Scholar
  7. Hannun, Y.A., Loomis, C.R., Merrill Jr., A.H., 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.PubMedGoogle Scholar
  8. Hathaway, G.M., and Traugh, J.A., 1982, Casein kinases-multipotential protein kinases, Curr. Topics Cell. Reg. 21: 101.Google Scholar
  9. Hirota, K., Hirota, T., Aguilera, G., and Catt, K.J., 1985, Hormone-induced redistribution of calcium-activated phospholipid-de-pendent protein kinase in pituitary gonadotrophs, J. Biol. Chem., 260: 3243.PubMedGoogle Scholar
  10. Job, D., Pirollet, F., Cochet, C., and Chambaz, E.M., 1979, Interaction of a casein kinase (G-type) with a specific endogenous inhibitor, FEBS Lett., 108: 508.PubMedCrossRefGoogle Scholar
  11. Kikkawa, U., Takai, Y., Minakuchi, R., Inohara, S., and Nashizuka, Y., 1982, Calcium-activated, phospolipid-dependent protein kinase from rat brain, J. Biol. Chem., 257: 13341.PubMedGoogle Scholar
  12. Kraft, A.S., and Anderson, W.B., 1983, Phorbol esters increase the amount of Ca, phospholipid-dependent protein kinase associated with plasma membrane, Nature, 301: 621.PubMedCrossRefGoogle Scholar
  13. Krebs, E.G., 1985, The phosphorylation of proteins: a major mechanism for biological regulation, Biochem. Soc. Trans. 13: 813.PubMedGoogle Scholar
  14. Kurokawa, M., Yokoyama, K., and Ishibashi, S., 1983, Polyamines stimulate the binding of hexokinase type II to mitochondria, Biochim. Biophys. Acta, 759: 92.PubMedCrossRefGoogle Scholar
  15. Leach, K.L., and Blumberg, P.M., 1985, Modulation of protein kinase C activity and [3H] phorbol 12, 13-dibutyrate binding by various tumor promoters in mouse brain cytosol, Cancer Res., 45: 1958.PubMedGoogle Scholar
  16. Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J., 1951, Protein measurement with the folin phenol reagent, J. Biol. Chem., 193: 265.PubMedGoogle Scholar
  17. Marinetti, G.V., 1962, Chromatographic separation, indentification and analysis of phosphatides, J. Lipid. Res., 3: 1.Google Scholar
  18. Martin-Sanz, P., Hopewell, R., and Brindley, D.N., 1985, Spermine promotes the translocation of phosphatidate phosphohydrolase from the cytosol to the microsomal fraction of rat liver and it enhances the effects of oleate in this respect, FEBS, 179: 262.CrossRefGoogle Scholar
  19. Meers, P., Hong, K., Bentz, J., and Papahadjopoulos, D., 1986, Spermine as a modulator of membrane fusion: interactions with acidic phospholipids, Biochemistry, 25: 3109.PubMedCrossRefGoogle Scholar
  20. Mezzetti, G., Moruzzi, M.S., Capone, G., and Barbiroli, B., 1980, Polyamine binding by a cytoplasmic factor in the duodenal mucosa of new-born chick, Biochem. Biophys. Res. Commun., 97: 222.PubMedCrossRefGoogle Scholar
  21. Mezzetti, G., Moruzzi, M., Monti, M.G., Piccinini, G. and Barbiroli, B., 1985, Polyamine-sensitive protein kinase from chick intestinal mucosa, Mol. Cell. Biochem., 66: 175.PubMedCrossRefGoogle Scholar
  22. Mezzetti, G., Moruzzi, M., Piccinini, G., Monti, M.G., and Barbiroli, B., 1986, Modulation of cyclic nucleotide-independent protein kinase from ckich intestine by naturally occurring polyamines and mucopolysaccharides, Mol. Cell. Biochem., 70: 141.PubMedCrossRefGoogle Scholar
  23. Moruzzi, M., Barbiroli, B., Monti, M.G., Tadolini, B., Hakim, G., and Mezzetti, G., 1987, Inhibitory action of polyamines on protein kinase C association to membranes, Biochem. J., 247: 175.PubMedGoogle Scholar
  24. Nilsson, O.S., and Dallner, G., 1977, Transverse asymmetry of phospholipids in subcellular membranes of rat liver, Biochim. Biophys. Acta, 464: 453.PubMedCrossRefGoogle Scholar
  25. Nishizuka, Y., 1986, Studies and perspectives of protein kinase C., Science, 233: 305.PubMedCrossRefGoogle Scholar
  26. Ohnishi, S., and Ito, T., 1974, Calcium-induced phase separation in phophatidylserine-phosphatidylcoline membranes, Biochemistry, 13: 881.CrossRefGoogle Scholar
  27. Qi, D., Schatzman, R.C., Mazzei, G.J., Turner, R.S., Raynor, R.L., Liao, S., and Kuo, J.F., 1983, Polyamine inhibit phospholipid-sensitive and calmodulin-sensitive Ca2+-dependent protein kinases, Biochem. J., 213: 281.PubMedGoogle Scholar
  28. Rubin, C.S., and Rosen, O.M., 1975, Protein phosphorylation, Ann. Rev. Biochem., 44: 831.PubMedCrossRefGoogle Scholar
  29. Sarkadi, B., Szasz, I., and Gardos, G., 1980, Characteristics and regulation of active calcium transport in inside-out red cell membrane vesicles, Biochim. Biophys. Acta, 598: 326.PubMedCrossRefGoogle Scholar
  30. Scatchard, G., 1949, The attractions of proteins for small molecules and ions, Ann. N.Y. Acad. Sci., 51: 660.CrossRefGoogle Scholar
  31. Schuber, F., Hong, K., Düzgünes, N., and Papahadjopoulos, D., 1983, Polyamines as Modulators of membrane fusion: aggregation and fusion of liposomes, Biochemistry, 22: 6134.PubMedCrossRefGoogle Scholar
  32. Schwantke, N., Le Bouffant, F., Dorée, M., and Le Peuch, C.J., 1985, Protein Kinase C: properties and possible role in cellular division and differentiation, Biochimie, 67: 1103.PubMedCrossRefGoogle Scholar
  33. Tabor, C.W., and Tabor, H., 1984, Polyamines, Ann. Rev. Biochem., 53: 749.PubMedCrossRefGoogle Scholar
  34. Tadolini, B., Cabrini, L., Varani, E., and Sechi, A.M., 1985, Spermine binding and aggregation of vesicles of different phospholipid composition, Biogenic Amines, 3: 87.Google Scholar
  35. Thams, P., Capito, K., and Hedeskov, C.J., 1986, An inhibitory role for polyamines in protein kinase C activation and insulin secretion in mouse pancreatic islets, Biochem. J., 237: 131.PubMedGoogle Scholar
  36. Walsh, M.P., Valentine, K.A., Neai, P.K., Carruthers, C.A., and Hollenberg, M.D., 1984, Ca-dependent hydrophobic-interaction chromatography, Biochem. J., 224-117.Google Scholar
  37. Wolf, M., Cuatrecasas, P., and Sahyoun, N., 1985a, Interaction of protein kinase C with membranes is regulated by Ca, phorbol esters, and ATP, J. Biol. Chem., 260: 15718.PubMedGoogle Scholar
  38. Wolf, M., Le Vine III, H., May Jr., W.S., Cuatrecasas, P. and Sahyoun, N., 1985b, A model for intracellular translocation of protein kinase C involving synergism between Ca and phorbol esters, Nature, 317: 546.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Maria Stella Moruzzi
    • 1
  • Giorgio Piccinini
    • 1
  • Bruna Tadolini
    • 1
    • 2
  • Maria Giuseppina Monti
    • 1
  • Bruno Barbiroli
    • 1
    • 3
  • Gabriele Mezzetti
    • 1
  1. 1.Istituto di Chimica BiologicaUniversità di ModenaItaly
  2. 2.Dipartimento di BiochimicaUniversità di BolognaItaly
  3. 3.Cattedra di Biologia MolecolareUniversité di BolognaItaly

Personalised recommendations