Phosphorylase kinase phosphorylates a brain protein which is influenced by repetitive synaptic activation

Abstract

SYNAPTIC systems from mammalian brain can now be studied in situ using a brain slice preparation which displays most of the electrophysiological characteristics observed in intact preparations1,2. We have been particularly interested in analysis of long-term potentiation (LTP), a marked and quasi-permanent increase in synaptic efficacy which is found in the hippocampal formation following a brief (1 s) train of repetitive stimulation3–6. Previous work from this laboratory demonstrated a strong correlation between induction of such LTP and the apparent phosphorylation of a 40,000 molecular weight protein in synaptic plasma membranes (SPM)7,8. Both LTP and the stimulation-dependent changes in the 40,000-MW protein were dependent on calcium and this cation has also recently been shown (ref. 9 and unpublished observations) to enhance the endogenous phosphorylation of a protein with a molecular weight of 40,000. If potentiation and the phosphorylation of the 40,000-MW protein are related, with calcium being required for both, then it is possible that a calcium-dependent protein kinase might be an intermediary enzyme in the two processes. We have therefore investigated the effect of exogeneous phosphorylase kinase (PBK; EC 2.7.1.38), a calcium-sensitive enzyme found in brain10,11, on the phosphorylation of the 40,000-MW protein. Since several laboratories have demonstrated cyclic AMP-dependent phosphorylation of several SPM proteins12–15, it was also of interest to test for the possibility that this nucleotide might be involved in the phosphorylation of the 40,000-MW protein. We report here that PBK produces a marked and highly specific phosphorylation of the 40,000-MW protein that we have previously shown to be affected by high frequency potentiating stimulation.

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References

  1. 1

    Yamamoto, C. Expl Brain Res. 14, 423–435 (1972).

    CAS  Article  Google Scholar 

  2. 2

    Lynch, G., Smith, R., Browning, M. & Deadwyler, S. Adv. Neurol. 12, 297–313 (1975).

    CAS  PubMed  Google Scholar 

  3. 3

    Bliss, T. & Lømo, T. J. Physiol., Land. 232, 331–356 (1973).

    CAS  Article  Google Scholar 

  4. 4

    Douglas, R. & Goddard, G. Brain Res. 86, 205–215 (1975).

    CAS  Article  Google Scholar 

  5. 5

    Schwartzkroin, P. & Wester, R. Brain Res. 89, 107–119 (1975).

    CAS  Article  Google Scholar 

  6. 6

    Dunwiddie, T. & Lynch, G. J. Physiol., Lond. 276, 353–367 (1978).

    CAS  Article  Google Scholar 

  7. 7

    Browning, M., Dunwiddie, T., Gispen, W. & Lynch, G. Neurosci. Abstr. 3, 1341 (1977).

    Google Scholar 

  8. 8

    Browning, M., Dunwiddie, T., Bennett, W., Gispen, W. & Lynch, G. Science 203, 60–62 (1979).

    ADS  CAS  Article  Google Scholar 

  9. 9

    Hershkowitz, M. Biochim. biophys. Acta 542, 274–283 (1978).

    CAS  Article  Google Scholar 

  10. 10

    Brostrum, C., Hunkeler, F. & Krebs, E. J. biol. Chem. 246, 1961–1967 (1971).

    Google Scholar 

  11. 11

    Ozawa, E. J. Neurochem. 20, 1487–1488 (1973).

    CAS  Article  Google Scholar 

  12. 12

    Johnson, E., Ueda, T., Maeno, H. & Greengard, P. J. biol. Chem. 247, 5650–5652 (1972).

    CAS  PubMed  Google Scholar 

  13. 13

    Ueda, T., Maeno, H. & Greengard, P. J. biol. Chem. 248, 8295–8305 (1973).

    CAS  PubMed  Google Scholar 

  14. 14

    Routtenberg, A. & Erlich, Y. Brain Res. 92, 415–430 (1975).

    CAS  Article  Google Scholar 

  15. 15

    Dunkley, P., Holmes, H. & Rodnight, R. Biochem. J. 163, 369–378 (1977).

    CAS  Article  Google Scholar 

  16. 16

    Kelly, P. & Luttges, M. J. Neurochem. 24, 1077–1079 (1975).

    CAS  Article  Google Scholar 

  17. 17

    Daegelen-Proux, D., Pierres, M., Alexandre, Y. & Dreyfus, J. Biochim. biophys. Acta 452, 398–405 (1976).

    CAS  Article  Google Scholar 

  18. 18

    Perry, S. & Cole, H. Biochem. J. 141, 733–743 (1974).

    CAS  Article  Google Scholar 

  19. 19

    O'Farrell, P. J. biol. Chem. 250, 4007–4021 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20

    Baker, P., Meves, H. & Ridgway, E. J. Physiol., Lond. 216, 70P–71P (1971).

    CAS  PubMed  Google Scholar 

  21. 21

    Baker, P., Hodgkin, A. & Ridgway, E. J. Physiol., Lond. 218, 709–755 (1971).

    CAS  Article  Google Scholar 

  22. 22

    Llinas, R., Blinks, J. & Nicholson, C. Science 176, 1127–1129 (1972).

    ADS  CAS  Article  Google Scholar 

  23. 23

    Katz, B. & Miledi, R. J. Physiol., Lond. 207, 789–801 (1970).

    CAS  Article  Google Scholar 

  24. 24

    Landowne, D. & Ritchie, J. J. Physiol., Lond. 212, 503–517 (1971).

    CAS  Article  Google Scholar 

  25. 25

    Moffett, D. & Lamonna, J. Brain Res. 152, 365–368 (1978).

    CAS  Article  Google Scholar 

  26. 26

    Folbergrova, J. Brain Res. 135, 337–346 (1977).

    CAS  Article  Google Scholar 

  27. 27

    Edwards, C., Nahorski, S. & Rogers, K. J. Neurochem. 22, 565–572 (1974).

    CAS  Article  Google Scholar 

  28. 28

    Moir, A., Cole, H. & Perry, S. Biochem. J. 161, 371–382 (1977).

    CAS  Article  Google Scholar 

  29. 29

    England, P., Stull, J., Huang, T. & Krebs, E. Metabolic Interconversion of Enzymes 3, 175–184 (1973).

    Google Scholar 

  30. 30

    Hartshorne, D. & Dreizen, P. Cold Spring Harb. Symp. quant. Biol. 37, 225–234 (1972).

    Article  Google Scholar 

  31. 31

    Horl, W., Jennissen, D. & Heilmeyer, L. Biochemistry 17, 759–766 (1978).

    CAS  Article  Google Scholar 

  32. 32

    Horl, W. & Heilmeyer, L. Biochemistry 17, 766–772 (1978).

    CAS  Article  Google Scholar 

  33. 33

    Sulakhe, P. & St Louis, P. Biochem. J. 164, 457–459 (1977).

    CAS  Article  Google Scholar 

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BROWNING, M., BENNETT, W. & LYNCH, G. Phosphorylase kinase phosphorylates a brain protein which is influenced by repetitive synaptic activation. Nature 278, 273–275 (1979). https://doi.org/10.1038/278273a0

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