Phosphatidylinositol Kinase, a Key Enzyme of Phosphatidylinositol Metabolism: Its Role in an Intracellular Second Messenger System

  • Zafiroula Georgoussi
  • Ludwig M. G. HeilmeyerJr.
Part of the NATO ASI Series book series (NSSA, volume 91)


It is now well established that many cell agonists, hormones or neurotransmitters called “first messengers” provoke intracellulary a concentration change of a “second messenger” like cyclic AMP, cyclic GMP or Ca2+ (for review: Dumont et al., 1981), (Fig. 1). An increase of these second messengers leads to saturation of specific receptor proteins which can be either regulatory proteins or domains of enzymes or in case of Ca2+, specific Ca2+ binding proteins, e. g. calmodulin.


Sarcoplasmic Reticulum Phosphatidic Acid Phosphatidic Acid Phosphatidylinositol Kinase Dependent Protein Kinase 
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.

Abbreviations used
















phosphatidic acid




cytidine diphosphate diacylglycerol


sarcoplasmic reticulum


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  1. Bell, R.L., Kennerly, D.A., Stanford, N. and Majerus, P.W., 1979, Diglyceride lipase: a pathway for arachidonate release from human platelets, Proc. Natl. Acad. Sci. USA, 76: 3238.PubMedCrossRefGoogle Scholar
  2. Berridge, M.J., 1981, Phosphatidylinositol hydrolysis: a multifunctional transducing mechanism, Molecular and Cellular Endocrinology, 24: 115.PubMedCrossRefGoogle Scholar
  3. Berridge, M.J., 1983, Rapid accumulation of inositol trisphosphate reveals that agonists hydrolyse polyphosphoinositides instead of phosphatidylinositol, Biochem. J., 212: 849.PubMedGoogle Scholar
  4. Berridge, M.J. and Irvine, R.F., 1984, in: “Cyclitols and Inositides”, Bleasdale, J., Eichberg, J. and Hauser, G., Humana Press.Google Scholar
  5. Berridge, M.J., 1984, Inositol trisphosphate and diacylglycerol as second messengers, Biochem. J., 220: 345.PubMedGoogle Scholar
  6. Buckley, J.T. and Hawthorne, J.N., 1972, Erythrocyte membrane polyphosphoinositide metabolism and the regulation of Ca2+ binding, J. Biol. Chem., 247: 7218.PubMedGoogle Scholar
  7. Cohen, P., 1973, The subunit structure of rabbit skeletal muscle phosphorylase kinase and the molecular basis of its activation reaction, Eur. J. Biochem., 34: 1.PubMedCrossRefGoogle Scholar
  8. Crabb, J.W. and Heilmeyer,L.M.G., Jr. 1984 a, Micropreparative protein purification by reversed-phase high-performance liquid chromatography, J. of Chromatography, 226: 129.CrossRefGoogle Scholar
  9. Crabb, J.W. and Heilmeyer, L.M.G., Jr. 1984 b, High performance liquid chromatography purification and structural characterization of the subunits of rabbit muscle phosphorylase kinase, J. Biol. Chem., 259: 6346.PubMedGoogle Scholar
  10. Dickneite, G., Jennissen, H.P. and Heilmeyer, L.M.G., Jr., 1978, Differentiation of two catalytic sites on phosphorylase kinase for phosphorylase b and troponin T phosphorylation, FEBS lett., 87: 297.PubMedCrossRefGoogle Scholar
  11. Dumont, J.E., Greengard, P. and Robinson, A.G., 1981, “Advances in Cyclic Nucleotide Research”, Raven Press, New York.Google Scholar
  12. Farese, R.V., 1983, The phosphatidate-phosphoinositide Cycle: An intracellular messenger system in the action of hormones and neurotransmitters, Metabolism, 32: 628.PubMedCrossRefGoogle Scholar
  13. Fischer, E.H., Alaba, I.O., Brautigan, D.L.,Malencik, D.A., Moeschler, H.I., Picton, C. and Procingwong, S., 1978, “Versatility of Proteins” (C.H. Li. ed), Academic Press, New York, 133.Google Scholar
  14. Gröschel-Stewart, U., Jennissen, H.P., Heilmeyer, L.M.G., Jr. and Varsanyi, M., 1978, Localization of Ca2+-dependent protein kinases in various tissues by the immunofluorescent technique, Int. J. Peptide Protein Res., 12: 177.CrossRefGoogle Scholar
  15. Hayakawa, T., Perkins, J.P. and Krebs, E.G., 1973, Studies on the subunit structure of rabbit skeletal muscle phosphorylase kinase, Biochemistry, 12: 574.PubMedCrossRefGoogle Scholar
  16. Hokin, M.R. and Hokin, L.E., 1958, Enzyme secretion and the incorporation of 32P into phospholipids of pancreas slices, J. Biol. Chem., 203: 967.Google Scholar
  17. Hokin, L.E. and Hokin, M.R., 1958, Phosphoinositides and protein secretion in pancreas slices, J. Biol. Chem., 233: 805.PubMedGoogle Scholar
  18. Hörl, W.H., Jennissen, H.P. and Heilmeyer, L.M.G., Jr., 1978, Evidence for the participation of a Ca2+ dependent protein kinase and a protein phosphatase in the regulation of the Ca2+ transport ATPase of the sarcoplasmic reticulum. I. Effect of inhibitors of the Ca2+ dependent protein kinase and protein phosphatase, Biochemistry, 17: 759.PubMedCrossRefGoogle Scholar
  19. Hörl, W.H. and Heilmeyer, L.M.G., Jr., 1978, Evidence for the participation of a Ca2+ dependent protein kinase and protein phosphatase in the regulation of the Ca2+ transport ATPase of the sarcoplasmic reticulum, II. Effect of phosphorylase kinase and phosphorylase phosphatase, Biochemistry, 17: 766.PubMedCrossRefGoogle Scholar
  20. Jennissen, H.P., Veh, R.W., Petersen, J.K.H. and Neubauer, H.P., 1979, Immunological studies of phosphorylase kinase on the subunit level, Hoppe Seyler’s Z. Physiol. Chem., 360: 293Google Scholar
  21. Kilimann, M.W. and Heilmeyer, L.M.G., Jr., 1982, Multiple Activities on phosphorylase kinase, 1. Characterization of three partial activities by their response to Cat+, Mg2+, Mn2+, pH and NH4C1 and effect of activation by phosphorylation and proteolysis, Biochemistry, 21: 1727.PubMedCrossRefGoogle Scholar
  22. Kilimann, M.W. and Heilmeyer, L.M.G., Jr. 1982, Multiple activities on phosphorylase kinase, 2. Different specificities towards the protein substrates, phosphorylase b, troponin and phosphorylase kinase, Biochemistry, 21: 1735.PubMedCrossRefGoogle Scholar
  23. Krebs, E.G., Love, D.S., Bratvold, G.E., Trayser, K.A., Meyer, W.L. and Fischer, E.H., 1964, Purification and properties of rabbit skeletal muscle phosphorylase b kinase, Biochemistry, 3: 1022.PubMedCrossRefGoogle Scholar
  24. Lapetina, E.G., Billah, M.M., Cuatrecasas, P., 1981, The initial action of thrombin on platelets. Conversion of phosphatidylinositol to phosphatidic acid preceding the production of arachidonic acid, J. Biol. Chem., 256: 5037.PubMedGoogle Scholar
  25. Lapetina, E.G., 1982, Regulation of arachidonic acid production: role of phospholipase C and A2, Trends Pharmacol. Sci., 3: 115.CrossRefGoogle Scholar
  26. Michell, R.H., Jafferji, S.S. and Jones, L.M., 1977, The possible involvement of phosphatidylinositol breakdown in the mechanism of stimulus-response coupling at receptors which control cell-surface calcium gates, Adv. Exp. Med., 83: 447.Google Scholar
  27. Michell, R.H., Kirk, C.J., 1981, Why is phosphatidylinositol degraded in response to stimulation of certain receptors? Trends Pharmacol. Sci., 2: 86.Google Scholar
  28. Michell, R.H., 1982, Inositol phospholipids and cell calcium, Cell Calcium, 3: 285.PubMedCrossRefGoogle Scholar
  29. Michell, R.H., 1982, Is phosphatidylinositol really out of the calcium gate? Nature, 296: 492.PubMedCrossRefGoogle Scholar
  30. Michell, R.H., 1983, Cal+ and protein kinase C: two synergistic cellular signals, Trends Biochem. Sci., 8: 263.CrossRefGoogle Scholar
  31. Nishizuka, Y., 1984, The role of protein kinase C in cell surface signal transduction and tumor promotion, Nature, 308: 693.PubMedCrossRefGoogle Scholar
  32. Penniston, J.T., 1982, Plasma Membrane Ca2+-Pumping ATPases, in: “Transport ATPases”, Carafoli, E. and Scarpa, A. ed., The New York Academy of Sciences, New York.Google Scholar
  33. Putney, J.W., Weiss, S.J., Van de Walle, C.M. and Haddes, R., 1980, Is phosphatidic acid a calcium ionophore under neurohumoral control, Nature, 284: 344.CrossRefGoogle Scholar
  34. Putney, J.W., 1981, Recent hypotheses regarding the phosphatidylinositol effect, Life Sciences, 29: 1183.PubMedCrossRefGoogle Scholar
  35. Reimann, E.M., Titani, K., Ericsson, L.H., Wade, R.D., Fischer, E.H., Walsh, K.A., 1984, Homology of the -subunit of phosphorylase b kinase with cAMP-dependet protein kinase, Biochemistry, in press.Google Scholar
  36. Skuster, J.R., Chan, J.K.F. and Graves, D.I., 1980, Isolation and properties of the catalytically active subunit of phosphorylase b kinase, J. Biol. Chem., 255: 2203.PubMedGoogle Scholar
  37. Sugimoto, Y., Whitman, M., Cantley, C.L. and Erikson, R.L., 1984, Evidence that the Rous sarcoma virus transforming gene product phosphorylates phosphatidylinositol and diacylglycerol, Prod. Natl. Acad. Sci., USA, 81: 2117.CrossRefGoogle Scholar
  38. Streb, H., Irvine, R.F., Berridge, M.J. and Schulz, I., 1983, Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4–5-trisphosphate, Nature, 306: 67.PubMedCrossRefGoogle Scholar
  39. Varsanyi, M., Gröschel-Stewart, U. and Heilmeyer, L.M.G., Jr., 1978, Characterization of a Ca2+-dependent protein kinase in skeletal muscle membranes of I-strain and wild-type mice, Eur. J. Biochem., 87: 331.PubMedCrossRefGoogle Scholar
  40. Varsanyi, M., and Heilmeyer, L.M.G., Jr., 1981, Phosphorylation of the 100.000 MR Ca2+ transport ATPase by Ca2+ or cyclic AMP dependent and independent protein kinases, FEBS Lett., 131: 223.PubMedCrossRefGoogle Scholar
  41. Varsanyi, M., Tölle, H.G., Heilmeyer, L.M.G., Jr., Dawson, R.M.C. and Irvine, R.F., 1983, Activation of sarcoplasmic reticular Ca2+ transport ATPase by phosphorylation of an associated phosphatidylinositol, The EMBO Journal, 2: 1543.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Zafiroula Georgoussi
    • 1
    • 2
  • Ludwig M. G. HeilmeyerJr.
    • 1
    • 2
  1. 1.The National Hellenic Research FoundationAthensGreece
  2. 2.Institut für Physiologische Chemie, Lehrstuhl 1Ruhr-Universität BochumBochumWest-Germany

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