The Journal of Membrane Biology

, Volume 104, Issue 1, pp 21–34 | Cite as

Evidence implicating protein kinase C in exocytosis from electropermeabilized bovine chromaffin cells

  • D. E. Knight
  • D. Sugden
  • P. F. Baker
Articles
Received:
Revised:

Summary

The calcium sensitivity of exocytosis from electroper-meabilized chromaffin cells is increased by activators of protein kinase C, such as TPA and certain phorbol esters, diacylglycerols, and mezerein. A range of putative inhibitors of protein kinase C block both the phorbol ester-sensitive component of secretion and also the underlying insensitive component. These inhibitors are also shown to inhibit medulla protein kinase C activity in vitro. The extent of secretion is reduced when electropermeabilized cells are exposed to Ca2+ levels much in excess of 50 μm. The onset of inhibition is faster than the relatively slow rate of Ca-dependent exocytosis and is insensitive to inhibitors of proteolysis. Adrenal medulla protein kinase C activity is also irreversibly inhibited by high Ca2+ concentrations. Both the secretory response and the protein kinase C activity in vitro have similar nucleotide and cation specificities. Although these data do not definitely establish an involvement of protein kinase C in exocytosis, none argue against it.

Key Words

exocytosis secretion calcium protein kinase C adrenal medulla catecholamine 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Baker, P.F. 1986. Protein kinase C and exocytosis.Prog. Zool. 33:265–274Google Scholar
  2. Baker, P.F., Knight, D.E. 1978. Calcium dependent exocytosis in bovine adrenal medullary cells with leaky plasma membranes.Nature (London) 276:620–622Google Scholar
  3. Batty, I.R., Nahorski, S.R., Irvine, R.F. 1985. Rapid formation of inositol 1,3,4,5-tetrakisphosphate following muscarinic receptor stimulation of rat cerebral cortical slices.Biochem. J. 232:211–215Google Scholar
  4. Berridge, M.J., Irvine, R.F. 1984. Inositol trisphosphate, a novel second messenger in cellular signal transduction.Nature (London) 312:315–321Google Scholar
  5. Bittner, M.A., Holz, R.W., Neubig, R.R. 1986. Guanine nucleotide effects on catecholamine secretion from digitonin-permeabilized adrenal chromaffin cells.J. Biol. Chem. 261:10182–10188Google Scholar
  6. Blackwell, G.J., Flower, R.J. 1983. Inhibition of phospholipase.Brit. Met. Bull. 39:260–264Google Scholar
  7. Breckenridge, L.J., Almers, W. 1987. Final steps in exocytosis observed in a cell with giant secretory granules.Proc. Natl. Acad. Sci. USA 84:1945–1949Google Scholar
  8. Brocklehurst, K.W., Lee, G., Pollard, H.B. 1986. Rapid purification and properties of protein kinase C from bovine adrenal medulla.Biosci. Rep. 6:749–757Google Scholar
  9. Brocklehurst, K.W., Pollard, B.P. 1985. Enhancement of Ca2+ induced catecholamine release by the phorbol ester TPA in digitonin-permeabilised cultured bovine adrenal chromaffin cells.FEBS Lett. 183:107–110Google Scholar
  10. Castagna, M., Takai, Y., Kaibuchi, K., Sano, K., Kikkawa, U., Nishizuka, Y. 1982. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol ester.J. Biol. Chem. 257:7847–7851Google Scholar
  11. Cockroft, S., Gomperts, B.D. 1985. Role of guanine nucleotide binding proteins in the activation of polyphosphoinositide phosphodiesterase.Nature (London) 314:534–536Google Scholar
  12. Ebeling, J.G., Vandenbark, G.R., Kuhn, J.J., Ganong, B.R., Bell, R.M., Niedel, J.E. 1985. Diacylglycerols mimic phorboldiester induction of leukemic cell differentiation.Proc. Natl. Acad. Sci. USA 82:815–819Google Scholar
  13. Ferrari, S., Marchiori, F., Borin, G., Pinna, L.A. 1985. Distinct structural requirements of Ca2+/phospholipid-dependent protein kinase (protein kinase C) and cAMP-dependent protein kinase as evidenced by synthetic peptide substrates.FEBS Lett. 184:72–77Google Scholar
  14. Gopalakrishna, R., Barsky, S.H., Thomas, T.P., Anderson, W.B. 1986. Factors influencing chelator-stable, detergent-extractable phorbol diester-induced membrane association of protein kinase C.J. Biol. Chem. 261:16438–16445Google Scholar
  15. Haslam, R.J., Davidson, M.M.L. 1984. Receptor induced diacylglycerol formation in permeabilised platelets: Possible role for a GTP binding protein.J. Rec. Res. 4:605–629Google Scholar
  16. Hidaka, H., Inagaki, M., Kawamoto, S., Sasaki, Y. 1984. Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C.Biochemistry 23:5036–5041Google Scholar
  17. Hidaka, H., Yamaki, T., Naka, M., Tanaka, T., Hayashi, H., Kobayashi, R. 1980. Calcium-regulated modulator protein interacting agents inhibit smooth muscle calcium-stimulated protein kinase and ATPase.Mol. Pharmacol. 17:66–72Google Scholar
  18. Hokin, M.R., Hokin, L.E. 1953. Enzyme secretion and the incorporation of [32P] into phospholipids of pancreatic slices.J. Biol. Chem. 203:967–977Google Scholar
  19. Holz, R.W. 1986. The role of osmotic forces in exocytosis from adrenal chromaffin cells.Annu. Rev. Physiol. 48:175–189Google Scholar
  20. Holz, R.W., Senter, R.A. 1986. Effects of osmolarity and ionic strength on secretion from adrenal chromaffin cells permeabilised with digitonin.J. Neurochem. 46:1835–1842Google Scholar
  21. Hu, G.-Y., Hvalby, O., Walaas, S.I., Albert, K.A., Skjeflo, P., Andersen, P., Greengard, P. 1987. Protein kinase C injection into hippocampal pyramidal cells elicits features of long term potentiation.Nature (London) 328:426–429Google Scholar
  22. Ido, M., Kazuo, S., Kikkawa, U., Nishizuka, Y. 1987. Phosphorylation of the EGF receptor from A431 epidermoid carcinoma cells by three distinct types of protein kinase C.FEBS Lett. 219:215–218Google Scholar
  23. Jetten, A.M., Ganong, B.R., Vanderbark, G.R., Shirley, J.E., Bell, R.M. 1985. Role of protein kinase C in diacylglycerol-mediated induction of ornithine decarboxylase and reduction of epidermal growth factor binding.Proc. Natl. Acad. Sci. USA 82:1941–1948Google Scholar
  24. Kariya, K., Takai, Y. 1987. Distinct functions of down-regulation sensitivity and resistant types of protein kinase C in rabbit aortic smooth muscle cells.FEBS Lett. 219:119–124Google Scholar
  25. Katoh, N., Raynor, R.L., Wise, B.C., Schatzmann, R.C., Turner, R.S., Helfman, D.M., Fain, J.N., Kuo, J.-F. 1982. Inhibition by melittin of phospholipid-sensitive and calmodulin-sensitive Ca2+-dependent protein kinases.Biochem. J. 202:217–224Google Scholar
  26. Katoh, N., Wise, B.C., Wrenn, R.W., Kuo, J-F. 1981. Inhibition by adriamycin of calmodulin-sensitive and phospholipid-sensitive calcium-dependent phosphorylation of endogenous proteins from heart.Biochem. J. 198:199–205Google Scholar
  27. Kikkawa, U., Nishizuka, Y. 1986. The role of protein kinase C in transmembrane signalling.Annu. Rev. Cell. Biol. 2:149–178Google Scholar
  28. Kishimoto, A., Kajikawa, N., Shiota, M., Nishizuka, Y. 1983. Proteolytic activation of calcium-activated, phospholipid-dependent protein kinase by calcium neutral protease.J. Biol. Chem. 258:1156–1164Google Scholar
  29. Knight, D.E. 1986. Botulinum toxin types A, B, and D inhibit catecholamine secretion from bovine adrenal medullary cells.FEBS Lett. 207:222–226Google Scholar
  30. Knight, D.E., Baker, P.F. 1982. Calcium dependence of catecholamine release from bovine adrenal medullary cells after exposure to intense electric fields.J. Membrane Biol. 68:107–140Google Scholar
  31. Knight, D.E., Baker, P.F. 1983. The phorbol ester TPA increases the affinity of exocytosis for Ca in leaky adrenal medullary cells.FEBS Lett. 160:98–100Google Scholar
  32. Knight, D.E., Baker, P.F. 1985. Guanine nucleotides and Ca-dependent exocytosis: Studies on two adrenal preparations.FEBS Lett. 189:345–349Google Scholar
  33. Knight, D.E., Niggli, V., Scrutton, M.C. 1984. Thrombin and activators of protein kinase C modulated the secretory response of permeabilised human platelets induced by Ca2+.Eur. J. Biochem. 143:437–446Google Scholar
  34. Knight, D.E., Tonge, D.A., Baker, P.F. 1985. Inhibition of exocytosis in bovine adrenal medullary cells by botulinum toxin type D.Nature (London) 317:719–721Google Scholar
  35. Knopf, J.L., Lee, M.H., Sultzman, L.A., Kriz, R.W., Loomis, C.R., Hewick, R.M., Bell, R.M. 1986. Cloning and expression of multiple protein kinase C cDNAs.Cell 46:491–502Google Scholar
  36. Kraft, A.S., Anderson, W.B. 1983a. Characterisation of cytosolic calcium-activated phospholipid-dependent protein kinase activity in embryonal carcinoma cells.J. Biol. Chem. 258:9178–9183Google Scholar
  37. Kraft, A.S., Anderson, W.B. 1983b. Phorbol esters increase the amount of Ca, phospholipid-dependent protein kinase associated with plasma membrane.Nature (London) 301:621–623Google Scholar
  38. Lubben, T.T., Traugh, J.A. 1983. Cyclic nucleotide-independent protein kinases from rabbit reticulocytes: Purification and characterisation of protease-activated kinase II.J. Biol. Chem. 258:13992–13997Google Scholar
  39. Maraganore, J.M. 1987. Structural elements for protein-phospholipid interactions may be shared in protein kinase C and phospholipases A2.Trends Biochem. Sci. 12:176–177Google Scholar
  40. Matthies, H.J.G., Palfrey, H.C., Hirning, L.D., Miller, R.J. 1987. Down regulation of protein kinase C in neuronal cells: Effects on neurotransmitter release.J. Neurosci. 7:1198–1206Google Scholar
  41. Mazzei, G.J., Katoh, N., Kuo, J.F. 1982. Polymyxin B is a more selective inhibitor for phospholipid-sensitive Ca2+-dependent protein kinase than for calmodulin sensitive Ca2+-dependent protein kinase.Biochem. Biophys. Res. Commun. 109:1129–1133Google Scholar
  42. Mazzei, G.J., Schatzman, R.C., Turner, R.S., Vogler, W.R., Kuo, J.F. 1984. Phospholipid-sensitive Ca2+-dependent protein kinase inhibition by R-24571, a calmodulin antagonist.Biochem. Pharmacol. 33:125–130Google Scholar
  43. Merritt, J.E., Taylor, C.W., Rubin, R.P., Putney, J.W. 1986. Evidence suggesting that a novel guanine nucleotide regulatory protein couples receptors to phospholipase C in exocrine pancreas.Biochem. J. 236:337–343Google Scholar
  44. Miyake, R., Tanaka, Y., Tsuda, T., Kaibuchi, K., Kikkawa, U., et al. 1984. Activation of protein kinase C by non-phorbol tumor promoter mezerein.Biochem. Biophys. Res. Commun. 121:649–656Google Scholar
  45. Murray, A.W., Fournier, A., Hardy, S.J. 1987. Proteolytic activation of protein kinase C: A physiological reaction?TIBS 12:53–54Google Scholar
  46. Nishizuka, Y. 1980. Three multifunctional protein kinase systems in transmembrane control.In: Molecular Biology, Biochemistry and Biophysics. Vol. 32, pp. 113–135. F. Chapeville and A.-L. Haenni, editors. Springer-Verlag. HeidelbergGoogle Scholar
  47. Nishizuka, Y. 1984. The role of protein kinase C in cell surface signal transduction and tumor promotion.Nature (London) 308:693–698Google Scholar
  48. Rink, T.J., Sanchez, A., Hallam, T.J. 1983. Diacylglycerol and phorbol esters stimulate secretion without raising cytoplasmic free calcium in human platelets.Nature (London) 305:317–319Google Scholar
  49. Shapira, R., Silberberg, S.D., Ginsburg, S., Rahamimoff, R. 1987. Activation of protein kinase C augments evoked transmitter release.Nature (London) 325:58–60Google Scholar
  50. Slaga, T.J., Fischer, S.M., Weeks, C.E., Klein-Szanto, A.J.P., Reiners, J. 1982. Studies on the mechanisms involved in multistage carcinogenisis in mouse skin.J. Supramol. Struct. Cell. Biochem. 18:99–119Google Scholar
  51. Takai, Y., Kishimoto, A., Nishizuka, Y. 1982. Calcium and phospholipid turnover as transmembrane signaling for protein phosphorylation.In: Calcium and Cell Function. Vol. 2, pp. 386–412. W.Y. Cheung, editor. Academic, New YorkGoogle Scholar
  52. TerBush, D.R., Holz, R.W. 1986. Effects of phorbol esters, diglyceride, and cholinergic agonists on the subcellular distribution of protein kinase C in intact or digitonin-permeabilised adrenal chromaffin cells.J. Biol. Chem. 261:17099–17106Google Scholar
  53. Touqui, L., Rothhut, B., Shaw, A.M., Fradin, A., Vargraftig, B.B., Russo-Marie, F. 1986. Platelet activation—a role for a 40K anti-phospholipase A2 protein indistinguishable from lipocortin.Nature (London) 31:177–180Google Scholar
  54. Weinstein, I.B. 1981. Current concepts and controversies in chemical carcinogenesis.J. Supramol. Struct. Cell. Biochem. 17:99–120Google Scholar
  55. Whitaker, M.J., Zimmerberg, J. 1987. Inhibition of secretory granule discharge during exocytosis in sea urchin eggs by polymer solutions.J. Physiol. (London) 389:527–539Google Scholar
  56. Wrenn, R.W., Katoh, N., Schatzman, R.C., Kuo, J.F. 1981. Inhibition by phenothiazine antipsychotic drugs of calcium-dependent phosphorylation of cerebral cortex proteins regulated by phospholipid or calmodulin.Life Sci. 29:725–733Google Scholar

Copyright information

© Springer-Verlag New York Inc 1988

Authors and Affiliations

  • D. E. Knight
    • 1
  • D. Sugden
    • 1
  • P. F. Baker
    • 1
  1. 1.MRC Secretory Mechanism Group, Division of Biomedical SciencesKings CollegeLondonEngland

Personalised recommendations