The Kinase C Substrate Protein B-50 and Feedback Control of Synaptic Signal Transduction

  • W. H. Gispen
  • P. N. E. De Graan
  • A. B. Oestreicher
  • P. Schotman
  • L. H. Schrama
  • M. de Wit
  • B. M. Spruijt
Conference paper
Part of the NATO ASI Series book series (volume 6)

Abstract

Muscarinic receptor activation of rat hippocampus results in phosphodiesteratic cleavage of phosphatidylinositol 4,5-bisphos-phate (PIP2) yielding diacylglycerol (DG) and inositoltrisphospha-te (IP3). The latter is thought to mobilize calcium from intracellular stores, whereas DG activates protein kinase C. The predominant substrate protein for kinase C in the synaptic plasma membrane is protein B-50 (Mr 48 kDa, IEP 4.5). An increase in the degree of phosphorylation of B-50 is parallelled by an inhibition of phosphatidylinositol 4-phosphate (PIP) kinase, presumably rendering less PIP2 available for further receptor-mediated hydrolysis. Peptides derived from melanocortins are known to inhibit protein kinase C and therefore may counteract the negative feedback exerted by DG. As B-50 in the adult rat brain is predominantly localized in presynaptic terminals, this effect of melanocortins may underly a presynaptic modulation of neurotransmission. The potential physiological importance of such a modulation is adstructed by the role of protein kinase C in ACTH-induced grooming behavior in the rat and by the modulation by ACTH of muscarinic-activated hydrolysis of PIP2 in rat hippocampal slices.

Keywords

Cellulose Hydrolysis Magnesium Albumin Amide 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aloyo, V.J., Zwiers, H. & Gispen, W.H. (1982) B-50 protein kinase and kinase C in rat brain. Progr. Brain Res. 56, 303–315.CrossRefGoogle Scholar
  2. Aloyo, V.J., Zwiers, H. & Gispen, W.H. (1983) Phosphorylation of B-50 by calcium-activated, phospholipid-dependent protein kinase and B-50 protein kinase. J. Neurochem. 41, 649–653.PubMedCrossRefGoogle Scholar
  3. Berridge, M.J. & Irvine, R.F. (1984) Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 312, 315–321.PubMedCrossRefGoogle Scholar
  4. De Graan, P.N.E., Van Hooff, C.O.M., Tilly, B.C., Oestreicher, A.B., Schotman, P. & Gispen, W.H. (1985) Phosphoprotein B-50 in nerve growth cones from fetal rat brain. Neurosci. Lett. 61, 235–241.PubMedCrossRefGoogle Scholar
  5. De Graan, P.N.E., Oestreicher, A.B., Schrama, L.H. & Gispen, W.H. (1986) Phosphoprotein B-50: Localization and function. Progr. Brain Res. 69, in press.Google Scholar
  6. Dunn, A.J., Green, E.J. & Isaacson, R.L. (1979) Intracerebral adrenocorticotropic hormone mediates novelty-induced grooming in the rat. Science 203, 281–283.PubMedCrossRefGoogle Scholar
  7. Eichberg, J., De Graan, P.N.E., Schrama, L.H. & Gispen, W.H. (1986) Dioctanoylglycerol and phorbol diesters enhance phosphorylation of phosphoprotein B-50 in native synaptic plasma membranes. Biochem. Biophys. Res. Commun. 136, 1007–1012.PubMedCrossRefGoogle Scholar
  8. Gispen, W.H., Wiegant, V.M., Greven, H.M. & De Wied, D. (1975) The induction of excessive grooming in the rat by intraventricular application of peptides derived from ACTH. Structure-activity studies. Life Sci. 17, 645–652.PubMedCrossRefGoogle Scholar
  9. Gispen, W.H., Zwiers, H., Wiegant, V.M., Schotman, P. & Wilson, J.E. (1979) The behaviorally active neuropeptide ACTH as neurohormone and neuromodulator. The role of cyclic nucleotides and membrane phosphoproteins. Adv. Exp. Med. Biol. 116, 199–224.PubMedGoogle Scholar
  10. Gispen, W.H., Van Dongen, C.J., De Graan, P.N.E., Oestreicher, A.B. & Zwiers, H. (1985a) The role of phosphoprotein B-50 in phosphoinositide metabolism in brain synaptic plasma membranes. In: Inositol and Phosphoinositides (J.E. Bleasdale, G. Häuser & J. Eichberg, eds.), pp. 399–413, Humana Press, Dallas.CrossRefGoogle Scholar
  11. Gispen, W.H., Leunissen, J.L.M., Oestreicher, A.B., Verkleij, A.J. & Zwiers, H. (1985b) Presynaptic localization of B-50 phosphoprotein: the ACTH-sensitive protein kinase substrate involved in rat brain polyphosphoinositide metabolism. Brain Res. 328, 381–385.PubMedCrossRefGoogle Scholar
  12. Gispen, W.H., Schrama, L.H. & Eichberg, J. (1985c) Stimulation of protein kinase C reduces ACTH-induced excessive grooming. Eur. J. Pharmacol. 114, 399–400.PubMedCrossRefGoogle Scholar
  13. Gispen, W.H. & Zwiers, H. (1985) Behavioral and neurochemical effects of ACTH. In: Handbook of Neurochemistry (A. Lajtha, ed.), Vol. 8, pp. 375–413, Plenum Press, New York.Google Scholar
  14. Kristjansson, G.I., Zwiers, H., Oestreicher, A.B. & Gispen, W.H. (1982) Evidence that the synaptic phosphoprotein B-50 is localized exclusively in nerve tissue. J. Neurochem. 39, 371–378.PubMedCrossRefGoogle Scholar
  15. Labarca, R., Janowsky, A., Patel, J. and Paul, S.M. (1984) Phorbol esters inhibit agonist-induced 3H-inositol-l-phosphate accumulation in rat hippocampal slices. Biochem. Biophys. Res. Commun. 123, 703–709.PubMedCrossRefGoogle Scholar
  16. Michell, B. (1986) Profusion and confusion. Nature 319, 176–177.PubMedCrossRefGoogle Scholar
  17. Nishizuka, Y. (1984a) Turnover of inositol phospholipids and signal transduction. Science 225, 1365–1370.PubMedCrossRefGoogle Scholar
  18. Nishizuka, Y. (1984b) The role of protein kinase C in cell surface signal transduction and tumor promotion. Nature 308, 693–697.PubMedCrossRefGoogle Scholar
  19. Oestreicher, A.B., Zwiers, H., Schotman, P. & Gispen, W.H. (1981) Immunohistochemical localization of a phosphoprotein (B-50) isolated from rat brain synaptosomal plasma membranes. Brain Res. Bull. 6, 145–153.PubMedCrossRefGoogle Scholar
  20. Oestreicher, A.B., Zwiers, H., Gispen, W.H. & Roberts, S. (1982) Characterization of infant rat cerebral cortical membrane proteins phosphorylated in vivo; identification of the ACTH-sensi-tive phosphoprotein B-50. J. Neurochem. 39, 683–692.PubMedCrossRefGoogle Scholar
  21. Oestreicher, A.B., Van Dongen, C.J., Zwiers, H. & Gispen, W.H. (1983) Affinity-purified anti-B-50 protein antibody: interference with the function of the phosphoprotein B-50 in synaptic plasma membranes. J. Neurochem. 41, 331–340.PubMedCrossRefGoogle Scholar
  22. Oestreicher, A.B., Dekker, L.V. & Gispen, W.H. (1986) A radioimmunoassay for the phosphoprotein B-50: distribution in rat brain. J. Neurochem. 46, 1366–1369.PubMedCrossRefGoogle Scholar
  23. Oestreicher, A.B. & Gispen, W.H. (1986) Comparison of the immunocytochemical distribution of the phosphoprotein B-50 in the cerebellum and hippocampus of immature and adult rat. Brain Res. 375, 267–279.PubMedCrossRefGoogle Scholar
  24. Schrama, L.H., De Graan, P.N.E., Eichberg, J. & Gispen, W.H. (1986) Feedback control of the inositol phospholipid response in rat brain is sensitive to ACTH. Eur. J. Pharmacol. 121, 403–404.PubMedCrossRefGoogle Scholar
  25. Sörensen, R.G., Kleine, L.P. & Mahler, H.R. (1981) Presynaptic localization of phosphoprotein B-50. Brain Res. Bull. 7, 57–61.PubMedCrossRefGoogle Scholar
  26. Van Rooijen, L.A.A., Rossowska, M. & Bazan, R.G. (1985) Inhibition of phosphatidylinositol 4-phosphate kinase by its product phosphatidylinositol 4,5-bisphosphate. Biochem. Biophys. Res. Commun. 126, 150–155.PubMedCrossRefGoogle Scholar
  27. Watson, S.J., Richard III, C.W. & Barchas, J.D. (1978) Adrenocorticotropin in rat brain: immunocytochemical localization in cells and axons. Science 275, 226–228.Google Scholar
  28. Zwiers, H., Veldhuis, D., Schotman, P. & Gispen, W.H. (1976) ACTH, cyclic nucleotides and brain protein phosphorylation in vitro. Neurochem. Res. 1, 669–677.CrossRefGoogle Scholar
  29. Zwiers, H., Wiegant, V.M., Schotman, P. & Gispen, W.H. (1977) Intraventricular administered ACTH and changes in rat brain protein phosphorylation: a preliminary report. In: Mechanism, Regulation and Special Functions of Protein Synthesis in the Brain (S. Roberts, A. Lajtha and W.H. Gispen, eds.), pp. 267–272, Elsevier/North-Holland Biomedical Press, Amsterdam.Google Scholar
  30. Zwiers, H., Wiegant, V.M., Schotman, P. & Gispen, W.H. (1978) ACTH-induced inhibition of endogenous rat brain protein phosphorylation in vitro: structure-activity. Neurochem. Res. 3, 455–463.PubMedCrossRefGoogle Scholar
  31. Zwiers, H., Tonnaer, J., Wiegant, V.M., Schotman, P. & Gispen, W.H. (1979) ACTH-sensitive protein kinase from rat brain membranes. J. Neurochem. 33, 247–256.PubMedCrossRefGoogle Scholar
  32. Zwiers, H., Schotman, P. & Gispen, W.H. (1980) Purification and some characteristics of an ACTH-sensitive protein kinase and its substrate protein in rat brain membranes. J. Neurochem. 34, 1689–1699.PubMedCrossRefGoogle Scholar
  33. Zwiers, H., Verhaagen, J., Van Dongen, C.J., De Graan, P.N.E. & Gispen, W.H. (1985) Resolution of rat brain synaptic phosphoprotein B-50 into multiple forms by two-dimensional electrophoresis: evidence for multi-site phosphorylation. J. Neurochem. 44, 1083–1090.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • W. H. Gispen
    • 1
  • P. N. E. De Graan
    • 1
  • A. B. Oestreicher
    • 1
  • P. Schotman
    • 1
  • L. H. Schrama
    • 1
  • M. de Wit
    • 1
  • B. M. Spruijt
    • 1
  1. 1.Division of Molecular Neurobiology, Rudolf Magnus Institute for Pharmacology, Laboratory for Physiological Chemistry, and Institute of Molecular Biology and Medical BiotechnologyUniversity of UtrechtUtrechtThe Netherlands

Personalised recommendations