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

Abstract

In this report, we show for the first time that ceramide‐1‐phosphate (C1P) stimulates the phosphatidylinositol 3‐kinase (PI3‐K)/protein kinase B (PKB) pathway, which is a major mechanism whereby growth factors promote cell survival. Also, C1P induced IκB phosphorylation, and enhanced the DNA binding activity of the transcription factor NF‐κB. 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 PI3‐K/PKB/ NF‐κB 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 PI3‐K/PKB pathway to promote cell survival.