Regulation of Plasma Membrane Phospholipase A2 Activity by Phosphorylation/Dephosphorylation: Is Glucocorticoid Action Mediated by Induction of Protein Phosphatase?

  • U. Zor
  • N. Reiss
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Phospholipase A2 (PLA2) is a key enzyme for the liberation of arachidonic acid — the main substrate for eicosanoid production. Regulation of membrane PLA2 activity is a complicated issue, involving second and third messengers, including protein kinases. The main protein kinase responsible for stimulating PLA2 activity may be protein kinase C (PKC), while another serine kinase, cyclic AMP-dependent protein kinase (PKA) switches it off. Glucocorticoids (GC) also inhibit PLA2 activity, via a mechanism that involves induction of protein synthesis. Our hypothesis suggests that at least one of these proteins is a protein phosphatase which reduces the level of phosphorylated PLA2, thereby suppressing its activity.


Protein Phosphatase Okadaic Acid PLA2 Activity Include Protein Kinase Phosphoprotein Phosphatase 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    U. Zor, E. Her, T. Harell, G. Fischer, Z. Naor, P. Braquet, E. Ferber, and N. Reiss, Arachidonic acid release by basophilic leukemia cells and macrophages stimulated by Ca2+ ionophores, antigen and diacylglycerol: essential role for protein kinase C and prevention by glucocorticosteroids, Biochim. Biophys. Acta 1091: 385 (1991).PubMedCrossRefGoogle Scholar
  2. 2.
    U. Zor, T. Harell, J. Hermon, E. Her, and E. Ferber, Novel mechanisms of glucocorticoid actions in inhibition of phospholipase A2 activity: Suppression of elevated [Ca2+]i, PI-PLC and PKC activity induced by Ca2+ ionophore and antigen, in: “Leukotrienes and Prostanoids in Health and Disease. New Trends Lipid Mediators Res.,” U. Zor, Z. Naor, and A. Danon, eds., Karger, Basel, p. 272 (1989).Google Scholar
  3. 3.
    J. N. Fain, M. A. Wallace, and J. H. Wojcikiewicz, Evidence for involvement of guanine nucleotide-binding regulatory proteins in the activation of phospholipases by hormones, FASEB J. 2: 2569 (1988).PubMedGoogle Scholar
  4. U. Zor, E. Her, P. Braquet, E. Ferber, and N. Reiss, A novel mechanism of glucocorticôid (GC) action in suppression of phospholipase A2 (PLA2) activity stimulated by Ca2+ ionophore A23187: Induction of protein phosphatases, in:“Advances in Prostaglandin, Thromboxane and Leukotriene Research,” B. Samuelsson, P. Ramwell, J. Vane, et al.,ed., Raven Press, New York, p. 265 (1991).Google Scholar
  5. 5.
    D. R. Alexander, and D. A. Cantrell, Kinases and phosphatases in T-cell activation, Immunology Today 10: 200 (1989).PubMedCrossRefGoogle Scholar
  6. 6.
    P. Cohen, The structure and regulation of protein phosphatases, Annu. Rev. Biochem. 58: 453 (1989).PubMedCrossRefGoogle Scholar
  7. 7.
    D. R. Alexander, J. M. Hexham, D. A. Cantrell, J. Goris, S. C. Lucas, J. D. Graves, and M. J. Crumpton, The regulation of protein phosphorylation by protein kinase C and phosphoprotein phosphatases in human T lymphocyte activation, Adv. Prot. Phosphatases 5: 313 (1989).Google Scholar
  8. 8.
    P. Cohen, and P. T. W. Cohen, Protein phosphatases come of age, J. Biol. Chem. 264: 21435 (1989).PubMedGoogle Scholar
  9. 9.
    M. S. Cyert, and J. Thorner, Putting it on and taking it off: Phosphoprotein phosphatase involvement in cell cycle regulation, Cell 57: 891 (1989).PubMedCrossRefGoogle Scholar
  10. 10.
    Z. Ahmad, and A. M. Watanabe, Evidence for physiological regulation of protein phosphatases, Adv. Prot. Phosphatases 5: 355 (1989).Google Scholar
  11. 11.
    K. H. W. Lau, J. R. Farley, and D. J. Baylink, Phosphotyrosyl protein phosphatases, Biochem. J. 257: 23 (1989).PubMedGoogle Scholar
  12. 12.
    P. Dent, A. Lavoinne, S. Nakielny, F. B. Caudwell, P. Watt, and P. Cohen, The molecular mechanism by which insulin stimulates glycogen synthesis in mammalian skeletal muscle, Nature 348: 302 (1990).PubMedCrossRefGoogle Scholar
  13. 13.
    P. Cohen, C. F. B. Holmes, and Y. Tsukitani, Okadaic acid: a new probe for the study of cellular regulation, TIBS 15: 98 (1990).PubMedGoogle Scholar
  14. 14.
    S. Shenolikar, and A. C. Naim, Protein phosphatases: recent progress, in: “Advances in Second Messenger and Phosphoprotein Research,” P. Greengard, and G. A. Robison, ed., Raven Press, Ltd., New York, p. 1 (1991).Google Scholar
  15. 15.
    G. Litwack, and S. Singer, Subcellular actions of glucocorticoids, in: “Biochemical Actions of Hormones,” G. Litwack, ed., Academic Press, N.Y., New York, London, vol. Il, p. 113 (1972).Google Scholar
  16. 16.
    M. J. Weiss, D. E. C. Cole, K. Ray, M. P. Whyte, M. A. Lafferty, R. A. Mulivor, and H. Harris, A missense mutation in the human liver/bone/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia, Proc. Natl. Acad. Sci. USA 85: 7666 (1988).PubMedCrossRefGoogle Scholar
  17. 17.
    C. MacKintosh, K. A. Beattie, S. Klumpp, P. Cohen, and G. A. Codd, Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants, FEBS Lett. 264: 187 (1990).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • U. Zor
    • 1
  • N. Reiss
    • 1
  1. 1.Department of Hormone ResearchThe Weizmann Institute of ScienceRehovotIsrael

Personalised recommendations