While the role of the group IVA Ca2+-dependent cytosolic phospholipase A2α (cPLA2α) in arachidonic acid (AA) metabolism has been well documented, that of its paralogue, Ca2+-independent group IVC PLA2 (cPLA2γ), has remained uncertain. Here we show, using a transfection strategy, that cPLA2γ has the ability to increase the spontaneous and stimulus-induced release of cellular fatty acids. The AA released by cPLA2γ was metabolized further to prostaglandin E2 via cyclo-oxygenase-1 (COX-1) in the immediate response, and via COX-2 in the delayed response. Mutation of the putative catalytic-centre residue Ser82 abrogated the AA-releasing function of cPLA2γ both in vitro and in vivo. Confocal microscopy revealed that cPLA2γ was distributed in the perinuclear endoplasmic reticulum membranes. Mutating the C-terminal prenylation site of cPLA2γ abrogated its intracellular membrane localization and cellular AA-releasing function, without reducing its enzyme activity in vitro. Our results indicate that cPLA2γ is the second cPLA2 enzyme that contributes to cellular AA metabolism and phospholipid remodelling under appropriate conditions.
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June 2003
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Research Article|
June 15 2003
Arachidonate release and prostaglandin production by group IVC phospholipase A2 (cytosolic phospholipase A2gamma)
Makoto MURAKAMI;
Makoto MURAKAMI
1
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
1To whom correspondence should be addressed (e-mail mako@pharm.showa-u.ac.jp).
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Seiko MASUDA;
Seiko MASUDA
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
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Ichiro KUDO
Ichiro KUDO
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
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Publisher: Portland Press Ltd
Received:
January 06 2003
Revision Received:
February 26 2003
Accepted:
March 03 2003
Accepted Manuscript online:
March 03 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 372 (3): 695–702.
Article history
Received:
January 06 2003
Revision Received:
February 26 2003
Accepted:
March 03 2003
Accepted Manuscript online:
March 03 2003
Citation
Makoto MURAKAMI, Seiko MASUDA, Ichiro KUDO; Arachidonate release and prostaglandin production by group IVC phospholipase A2 (cytosolic phospholipase A2gamma). Biochem J 15 June 2003; 372 (3): 695–702. doi: https://doi.org/10.1042/bj20030061
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