Regulation of Plasma Membrane Phospholipase A2 Activity by Phosphorylation/Dephosphorylation: Is Glucocorticoid Action Mediated by Induction of Protein Phosphatase?
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.
KeywordsProtein Phosphatase Okadaic Acid PLA2 Activity Include Protein Kinase Phosphoprotein Phosphatase
Unable to display preview. Download preview PDF.
- 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.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
- 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
- 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
- 10.Z. Ahmad, and A. M. Watanabe, Evidence for physiological regulation of protein phosphatases, Adv. Prot. Phosphatases 5: 355 (1989).Google Scholar
- 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.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