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FEBS Lett. 2005 Jul 4;579(17):3744-50.

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

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Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of the Basque Country, P.O. Box 644, 48080 Bilbao, Spain.


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 IkappaB phosphorylation, and enhanced the DNA binding activity of the transcription factor NF-kappaB. 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-kappaB 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.

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