Perinuclear localization of cytosolic phospholipase A2α is important but not obligatory for coupling with cyclooxygenases

FEBS Letters

Das, Sudipto²  Cho, Wonhwa²  Murakami, Makoto¹  Kim, Young-Jun²  Kudo, Ichiro¹ 

[1] Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan;Department of Chemistry, University of Illinois, Chicago, IL 60607, USA

关键词: Phospholipase A2;    Cyclooxygenase;    Arachidonic acid;    Prostaglandin;    C2 domain;    PLA2;    phospholipase A2;    cPLA2;    cytosolic phospholipase A2;    sPLA2;    secretory PLA2;    iPLA2;    Ca2+-independent PLA2;    COX;    cyclooxygenase;    5-LO;    5-lipoxygenase;    AA;    arachidonic acid;    PG;    prostaglandin;    LT;    leukotriene;    PKC;    protein kinase C;    EGFP;    enhanced green fluorescent protein;    IL-1;    interleukin-1;    FCS;    fetal calf serum;    WT;    wild-type;    HEK;    human embryonic kidney;    PC;    phosphatidylcholine;   

DOI  :  10.1016/S0014-5793(03)00596-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In response to Ca²⁺ signaling, cytosolic phospholipase A₂α (cPLA₂α) translocates from the cytosol to the perinuclear membrane, where downstream eicosanoid-synthetic enzymes, such as cyclooxygenase (COX), are localized. Although the spatiotemporal perinuclear colocalization of cPLA₂α and COXs has been proposed to be critical for their functional coupling leading to prostanoid production, definitive evidence for this paradigm has remained elusive. To circumstantiate this issue, we took advantage of a chimeric cPLA₂α mutant harboring the C2 domain of protein kinase Cα, which translocates to the plasma membrane following cell activation. Transfection analyses of the native or chimeric cPLA₂α in combination with COX-1 or COX-2 revealed that, even though the arachidonate-releasing capacities of native and mutant cPLA₂α were comparable, prostaglandin production by mutant cPLA₂α was markedly impaired as compared with that by native cPLA₂α. We thus conclude that the perinuclear localization of cPLA₂α is preferential, even if not obligatory, for efficient coupling with COXs.

【 授权许可】

Unknown