Ceramide-1-phosphate promotes cell survival through activation of the phosphatidylinositol 3-kinase/protein kinase B pathway

In this report, we show for the first time that ceramide- 1-phosphate (C1P) stimulates the phosphatidylinositol 3-kinase (P13-K)/protein kinase B (PKB) pathway, which is a major mechanism whereby growth factors promote cell survival. Also, C1P induced licB phosphorylation, and enhanced the DNA binding activity of the transcription factor NF-kappa B. Apoptotic macrophages showed a marked reduction of Bcl-X-L levels, and this was prevented by C1P. These findings suggest that C1P blocks apoptosis, at least in part, by stimulating the P13-K/ PKB/ NF-kappa B pathway and maintaining the production of antiapoptotic Bcl-X-L.Based on these and our previous observations, we propose a working model for C1P in which inhibition of acid sphingomyelinase and the subsequent decrease in ceramide levels would allow cell signaling through stimulation of the P13-K/PKB pathway to promote cell survival. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.