| First Author | Lamour NF | Year | 2009 |
| Journal | J Biol Chem | Volume | 284 |
| Issue | 39 | Pages | 26897-907 |
| PubMed ID | 19632995 | Mgi Jnum | J:155510 |
| Mgi Id | MGI:4414627 | Doi | 10.1074/jbc.M109.001677 |
| Citation | Lamour NF, et al. (2009) Ceramide 1-phosphate is required for the translocation of group IVA cytosolic phospholipase A2 and prostaglandin synthesis. J Biol Chem 284(39):26897-907 |
| abstractText | Little is known about the regulation of eicosanoid synthesis proximal to the activation of cytosolic phospholipase A(2)alpha (cPLA(2)alpha), the initial rate-limiting step. The current view is that cPLA(2)alpha associates with intracellular/phosphatidylcholine-rich membranes strictly via hydrophobic interactions in response to an increase of intracellular calcium. In opposition to this accepted mechanism of two decades, ceramide 1-phosphate (C1P) has been shown to increase the membrane association of cPLA(2)alpha in vitro via a novel site in the cationic beta-groove of the C2 domain (Stahelin, R. V., Subramanian, P., Vora, M., Cho, W., and Chalfant, C. E. (2007) J. Biol. Chem. 282, 20467-204741). In this study we demonstrate that C1P is a proximal and required bioactive lipid for the translocation of cPLA(2)alpha to intracellular membranes in response to inflammatory agonists (e.g. calcium ionophore and ATP). Last, the absolute requirement of the C1P/cPLA(2)alpha interaction was demonstrated for the production of eicosanoids using murine embryonic fibroblasts (cPLA(2)alpha(-/-)) coupled to 'rescue' studies. Therefore, this study provides a paradigm shift in how cPLA(2)alpha is activated during inflammation. |
