Protein Kinase C in Neuronal Cell Growth and Differentiation

  • J. F. Kuo
Conference paper
Part of the NATO ASI Series book series (volume 43)


Protein kinase C (PKC) system is particularly predominant in nervous tissue compared to other tissues as indicated by a high level of the enzyme activity (Kuo et al., 1980) or amount (Girard et al., 1986; Yoshida et al., 1988) and by an abundant occurrence of its substrate proteins (Wrenn et al., 1980). It is likely, therefore, that PKC plays a pivotal role in neuronal function and regulation. In this chapter, I summarized some of our work on immunocytochemical localization of PKC and phosphorylation of endogenous proteins in brain and neuroblastoma cells as they are related to development and differentiation.


Purkinje Cell Neurite Outgrowth Myelin Basic Protein Experimental Allergic Encephalomyelitis Dependent Protein Kinase 
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  1. Akers RF, Lovinger DM, Colley PA, Linden DJ, Routenberg A (1986) Translocation of protein kinase C activity may mediate hippocampal long-term potentiation. Science 132: 587–589CrossRefGoogle Scholar
  2. Albert KA, Walaas SI, Wang JK-T, Greengard P (1986) Widespread occurrence of “87 kDa” protein, a major specific substrate for protein kinase C. Proc Natl Acad Sci USA 83: 2822–2826PubMedCrossRefGoogle Scholar
  3. Aloyo VJ, Zwiers H, and Gispen WH (1983) Phosphorylation of B-50 protein by calcium-activated phospholipid-dependent protein kinase and B-50 protein kinase. J Neurochem 41: 649–653PubMedCrossRefGoogle Scholar
  4. Altman J. (1972) Postnatal development of cerebellar cortex in rat. H. Phases in the maturation of Purkinje cells and the molecular layer. J Comp Neurol 145: 399–464PubMedCrossRefGoogle Scholar
  5. Blackshear PJ, Wen L, Glynn BP, Witters LA (1986) Protein kinase C-stimulated phosphorylation in vitro of a Mr 80,000 protein phosphorylated in response to phorbol esters and growth factors in intact fibroblasts. Distinction from protein kinase C and prominence in brain. J Biol Chem 261: 1459–1469PubMedGoogle Scholar
  6. Chou FC-H, Chou C-HJ, Fritz RB and Kibler RF (1980) Prevention of experimental allergic encephalomyelitis in Lewis rats with peptide 68–88 of guinea pig myelin basic protein. Ann Neurol 7: 336–339PubMedCrossRefGoogle Scholar
  7. Girard PR, Mazzei GJ, Kuo JF (1986) Immunoquantitation of Phospholipid/Ca2+-dependent protein kinase and its fragments. Tissue levels, subcellular distribution and ontogenetic changes in brain. J Biol Chem 261: 370–375PubMedGoogle Scholar
  8. Girard PR, Mazzei GJ, Wood JG, Kuo JF (1985) Polyclonal antibodies to phospholipid/Ca2+-dependent protein kinase and immunocytochemical localization of the enzyme in rat brain. Proc Natl Acad Sci USA 82: 3030–3034.PubMedCrossRefGoogle Scholar
  9. Girard PR, Wood JG, Freschi JE, Kuo JF (1988) Immunocytochemical localization of protein kinase C in developing brain tissue and in primary neuronal culture. Devel Biol 126: 98–107CrossRefGoogle Scholar
  10. Girard PR, Wood JG, Freschi JE, Kuo JF (1988) Immunocytochemical localization of protein kinase C in developing brain tissue and in primary neuronal culture. Devel Biol 126: 98–107CrossRefGoogle Scholar
  11. Hall FL, Fernyhough P, Ishii DN, Vulliet PR (1988) Suppression of nerve growth factor-directed neurite outgrowth in PC12 cells by sphingosine, an inhibitor of protein kinase C. J Biol Chem 263: 4460–4466PubMedGoogle Scholar
  12. Jacobson RD, Virag I, Skene JHP (1986) A protein associated with axon growth, GAP-43, is widely distributed and developmentally regulated in rat CNS. J Neurochem 6: 1843–1855Google Scholar
  13. Kiss Z, Deli E, Shoji M, Koeffler HP, Pettit GR, Bogler WR, Kuo JF (1987) Differential effects of various protein kinase C activators on protein phosphorylation in human acute myeloblastic leukemia cell line KG-1 and its phorbol ester-resistant subline KG-la. Cancer Res 47: 1302–1307PubMedGoogle Scholar
  14. Kuo JF, Andersson RGG, Wise BC, Mackerlova L, Salomonsson I, Brackett NL, Shoji M, Wrenn RW (1980). Calcium-dependent protein kinases: Widespread occurrence in various tissues and phyla of animal kingdom and comparison of the effects of phospholipid, calmodulin and trifluoperazine. Proc Natl Acad Sci USA 77: 7039–7043PubMedCrossRefGoogle Scholar
  15. Meiri KF, Pfenninger KH, Willard MB (1986) Growth associated protein, GAP-43, a polypeptide that is induced when neurons extend axons, is a component of growth cones and corresponds to pp46, a major polypeptide of a subcellular fraction enriched in growth cones. Proc Natl Acad Sci USA 83: 3537–3541PubMedCrossRefGoogle Scholar
  16. Ouimet CC, McGuinness TL, Greengard P (1984) Immunocytochemisal localization of calcium/calmodulindependent protein kinase II in rat brain. Proc Nat Acad Sci USA 81: 5604–5608PubMedCrossRefGoogle Scholar
  17. Rozengurt E, Rodriguez-Pena M, Smith KA (1983) Phorbol esters, phospholipase C, and growth factors rapidly stimulate the phosphorylation of a Mr 80,000 protein in intact quiescent 3T3 cells. Proc Natl Acad Sci USA 80: 7244–7248PubMedCrossRefGoogle Scholar
  18. Smith BM, Colburn NH (1988) Protein kinase C and its substrates in tumor promoter-sensitive and resistant cells. J Biol Chem 263: 6424–6431PubMedGoogle Scholar
  19. Spinell W, Sonnenfeld KH, Ishii DN (1982) Effects of phorbol ester tumor promoters and nerve growth factor on neurite outgrowth in cultured human neuroblastoma cells. Cancer Res 42: 5067–5073Google Scholar
  20. Turner RS, Chou C-HJ, Kibler RF, Kuo JF (1982) Basic protein in brain mye,4n is phosphorylated by endogenous phospholipidsensitive Ca -dependent protein kinase. J Neurochem 39: 1397–1404PubMedCrossRefGoogle Scholar
  21. Turner RS, Raynor RL, Mazzei GJ, Girard PR, Kup JF (1984) Developmental studies of phospholipid-sensitive Ca ±dependent protein kinase and its substrates and phophoprotein phosphatases in rat brain. Proc Natl Acad Sci USA 81: 3143–3147PubMedCrossRefGoogle Scholar
  22. Wise BC, Glass DB, Chou C-HJ, Raynor RL, Katoh N, Schtazman RC, Turner RS, Kibler RF, Kuo JF (1982) Phospholipid-sensitive Ca -dependent protein kinase from heart. II. Substrate specificity and inhibition by various agents. J Biol Chem 257: 8489–8495PubMedGoogle Scholar
  23. Wolfman A, Wingrove TG, Blackshear PJ, Macara IG (1987) Down-regulation of protein kinase C and of an endogenous 80kDa substrate in transformed fibroblasts. J Biol Chem 262: 16546–16552PubMedGoogle Scholar
  24. Wood JG, Girard PR, Mazzei GJ, Kuo JF (1986) Immunocytochemical localization of protein kinase C in identified neuronal compartments of rat brain. J Neurosci 6: 2571–2577PubMedGoogle Scholar
  25. Wrenn RW, Katoh N, Wise BC, Kuo JF (1980) Stimulation of phosphtidylserine and calmodulin of calcium-dependent phosphorylation of endogenous proteins from cerebral cortex. J Biol Chem 255: 12042–12046PubMedGoogle Scholar
  26. Yoshida Y, Huang FL, Nakabayashi H, Huang K-P (1988) Tissue distribution and developmental expression of protein kinase C isozymes. J Biol Chem 263: 9868–9873PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • J. F. Kuo
    • 1
  1. 1.Department of PharmacologyEmory University School of MedicineAtlantaUSA

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