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Cited by 219

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Cytosolic Phospholipase A2 Is Required for Macrophage Arachidonic Acid Release by Agonists That Do and Do Not Mobilize Calcium

Open access
Gijón, Miguel A., Spencer, Diane M., Siddiqi, Abdur R., Bonventre, Joseph V., Leslie, Christina C.·2000·Journal of Biological Chemistry

Abstract

The 85-kDa cytosolic phospholipase A(2) (cPLA(2)) mediates agonist-induced arachidonic acid release and eicosanoid production. Calcium and phosphorylation on Ser-505 by mitogen-activated protein kinases (MAPKs) regulate cPLA(2). Arachidonic acid release and eicosanoid production induced by stimuli that do (A23187, zymosan) or do not (phorbol myristate acetate (PMA), okadaic acid) mobilize calcium were quantitatively suppressed in cPLA(2)-deficient mouse peritoneal macrophages. The contribution of MAPKs to cPLA(2)-mediated arachidonic acid release was investigated. Both extracellular signal-regulated kinases (ERKs) and p38 contributed to cPLA(2) phosphorylation on Ser-505. However, although ERK inhibition did not affect A23187-induced arachidonic acid release, it suppressed zymosan-, PMA-, and okadaic acid-induced arachidonic acid release under conditions where phosphorylation of cPLA(2) on Ser-505 was unaffected. This indicates an additional regulatory mechanism for the ERK pathway. A role for transcriptional regulation is suggested by data showing that cycloheximide and actinomycin D inhibited arachidonic acid release induced by zymosan, PMA and, okadaic acid but not by A23187. Our results show that MAPK pathways contribute to arachidonic acid release in macrophages through alternative mechanisms in addition to their ability to phosphorylate cPLA(2) on Ser-505 and suggest a role for new protein synthesis.

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Metadata

Authors
Gijón, M. A., Spencer, D. M., Siddiqi, A. R., Bonventre, J. V., & Leslie, C. C.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2000-06
Volume
275
Issue
26
Pages
20146-20156
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2033072622
Cited by
219
References
3
FWCI
10.11
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Cytosolic Phospholipase A2 Is Required for Macrophage Arachidonic Acid Release by Agonists That Do and Do Not Mobilize Calcium. https://app.cochat.ai/papers/10.1074/jbc.m908941199
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Gijón, M. A., Spencer, D. M., Siddiqi, A. R., Bonventre, J. V., & Leslie, C. C. (2000). Cytosolic Phospholipase A2 Is Required for Macrophage Arachidonic Acid Release by Agonists That Do and Do Not Mobilize Calcium. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m908941199

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