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. © 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
Murakami, M., Das, S., Kim, Y. J., Cho, W., & Kudo, I. (2003). Perinuclear localization of cytosolic phospholipase A2α is important but not obligatory for coupling with cyclooxygenases. FEBS Letters, 546(2–3), 251–256. https://doi.org/10.1016/S0014-5793(03)00596-9