Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1996 Oct 1;319(Pt 1):17–20. doi: 10.1042/bj3190017

Tumour necrosis factor-alpha-induced phosphorylation and activation of cytosolic phospholipase A2 are abrogated by an inhibitor of the p38 mitogen-activated protein kinase cascade in human neutrophils.

W H Waterman 1, T F Molski 1, C K Huang 1, J L Adams 1, R I Sha'afi 1
PMCID: PMC1217729  PMID: 8870643

Abstract

The role of the newly identified p38 mitogen-activated protein kinase (MAP kinase) in terminally differentiated cells, such as human neutrophils, is totally unknown. In order to examine the possible role of this MAP kinase in the phosphorylation and activation of cytoplasmic phospholipase A2 (cPLA2), we tested the effect of the recently synthesized inhibitor of p38 MAP kinase, SB 203580, on the phosphorylation and activation of both p38 MAP kinase and cPLA2. We found that while tumour necrosis factor-alpha (TNF-alpha)-stimulated tyrosine phosphorylation of p38 MAP kinase is affected only slightly by SB 203580, its stimulated kinase activity is greatly reduced in human neutrophils in suspension treated with this inhibitor. Furthermore, the TNF-alpha-stimulated phosphorylation and activation of cPLA2 are completely abolished in cells treated with SB 203580. Based on these data, it is reasonable to conclude that an SB 203580-sensitive kinase, or kinases and/or phosphatases, are involved in the phosphorylation and activation of cPLA2 in intact human neutrophils in suspension stimulated by TNF-alpha. The possible role of the p38 MAP kinase cascade in the phosphorylation and activation of cPLA2 is discussed.

Full Text

The Full Text of this article is available as a PDF (263.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bauldry S. A., Wooten R. E., Bass D. A. Activation of cytosolic phospholipase A2 in permeabilized human neutrophils. Biochim Biophys Acta. 1996 Jan 19;1299(2):223–234. doi: 10.1016/0005-2760(95)00207-3. [DOI] [PubMed] [Google Scholar]
  2. Börsch-Haubold A. G., Kramer R. M., Watson S. P. Cytosolic phospholipase A2 is phosphorylated in collagen- and thrombin-stimulated human platelets independent of protein kinase C and mitogen-activated protein kinase. J Biol Chem. 1995 Oct 27;270(43):25885–25892. doi: 10.1074/jbc.270.43.25885. [DOI] [PubMed] [Google Scholar]
  3. Channon J. Y., Leslie C. C. A calcium-dependent mechanism for associating a soluble arachidonoyl-hydrolyzing phospholipase A2 with membrane in the macrophage cell line RAW 264.7. J Biol Chem. 1990 Apr 5;265(10):5409–5413. [PubMed] [Google Scholar]
  4. Clark J. D., Lin L. L., Kriz R. W., Ramesha C. S., Sultzman L. A., Lin A. Y., Milona N., Knopf J. L. A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-dependent translocation domain with homology to PKC and GAP. Cell. 1991 Jun 14;65(6):1043–1051. doi: 10.1016/0092-8674(91)90556-e. [DOI] [PubMed] [Google Scholar]
  5. Cuenda A., Rouse J., Doza Y. N., Meier R., Cohen P., Gallagher T. F., Young P. R., Lee J. C. SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1. FEBS Lett. 1995 May 8;364(2):229–233. doi: 10.1016/0014-5793(95)00357-f. [DOI] [PubMed] [Google Scholar]
  6. English D., Andersen B. R. Single-step separation of red blood cells. Granulocytes and mononuclear leukocytes on discontinuous density gradients of Ficoll-Hypaque. J Immunol Methods. 1974 Aug;5(3):249–252. doi: 10.1016/0022-1759(74)90109-4. [DOI] [PubMed] [Google Scholar]
  7. Fouda S. I., Molski T. F., Ashour M. S., Sha'afi R. I. Effect of lipopolysaccharide on mitogen-activated protein kinases and cytosolic phospholipase A2. Biochem J. 1995 Jun 15;308(Pt 3):815–822. doi: 10.1042/bj3080815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goldberg H. J., Viegas M. M., Margolis B. L., Schlessinger J., Skorecki K. L. The tyrosine kinase activity of the epidermal-growth-factor receptor is necessary for phospholipase A2 activation. Biochem J. 1990 Apr 15;267(2):461–465. doi: 10.1042/bj2670461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gould G. W., Cuenda A., Thomson F. J., Cohen P. The activation of distinct mitogen-activated protein kinase cascades is required for the stimulation of 2-deoxyglucose uptake by interleukin-1 and insulin-like growth factor-1 in KB cells. Biochem J. 1995 Nov 1;311(Pt 3):735–738. doi: 10.1042/bj3110735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kramer R. M., Roberts E. F., Hyslop P. A., Utterback B. G., Hui K. Y., Jakubowski J. A. Differential activation of cytosolic phospholipase A2 (cPLA2) by thrombin and thrombin receptor agonist peptide in human platelets. Evidence for activation of cPLA2 independent of the mitogen-activated protein kinases ERK1/2. J Biol Chem. 1995 Jun 16;270(24):14816–14823. doi: 10.1074/jbc.270.24.14816. [DOI] [PubMed] [Google Scholar]
  11. Lin L. L., Lin A. Y., Knopf J. L. Cytosolic phospholipase A2 is coupled to hormonally regulated release of arachidonic acid. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6147–6151. doi: 10.1073/pnas.89.13.6147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lin L. L., Wartmann M., Lin A. Y., Knopf J. L., Seth A., Davis R. J. cPLA2 is phosphorylated and activated by MAP kinase. Cell. 1993 Jan 29;72(2):269–278. doi: 10.1016/0092-8674(93)90666-e. [DOI] [PubMed] [Google Scholar]
  13. Nahas N., Molski T. F., Fernandez G. A., Sha'afi R. I. Tyrosine phosphorylation and activation of a new mitogen-activated protein (MAP)-kinase cascade in human neutrophils stimulated with various agonists. Biochem J. 1996 Aug 15;318(Pt 1):247–253. doi: 10.1042/bj3180247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nahas N., Waterman W. H., Sha'afi R. I. Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes phosphorylation and an increase in the activity of cytosolic phospholipase A2 in human neutrophils. Biochem J. 1996 Jan 15;313(Pt 2):503–508. doi: 10.1042/bj3130503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Piomelli D. Arachidonic acid in cell signaling. Curr Opin Cell Biol. 1993 Apr;5(2):274–280. doi: 10.1016/0955-0674(93)90116-8. [DOI] [PubMed] [Google Scholar]
  16. Qiu Z. H., Leslie C. C. Protein kinase C-dependent and -independent pathways of mitogen-activated protein kinase activation in macrophages by stimuli that activate phospholipase A2. J Biol Chem. 1994 Jul 29;269(30):19480–19487. [PubMed] [Google Scholar]
  17. Raingeaud J., Gupta S., Rogers J. S., Dickens M., Han J., Ulevitch R. J., Davis R. J. Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J Biol Chem. 1995 Mar 31;270(13):7420–7426. doi: 10.1074/jbc.270.13.7420. [DOI] [PubMed] [Google Scholar]
  18. Smith W. L. The eicosanoids and their biochemical mechanisms of action. Biochem J. 1989 Apr 15;259(2):315–324. doi: 10.1042/bj2590315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Waterman W. H., Sha'afi R. I. A mitogen-activated protein kinase independent pathway involved in the phosphorylation and activation of cytosolic phospholipase A2 in human neutrophils stimulated with tumor necrosis factor-alpha. Biochem Biophys Res Commun. 1995 Apr 6;209(1):271–278. doi: 10.1006/bbrc.1995.1499. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES