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

被引:133
作者
Gómez-Muñoz, A
Kong, JY
Parhar, K
Wang, SW
Gangoiti, P
González, M
Eivemark, S
Salh, B
Duronio, V
Steinbrecher, UP
机构
[1] Univ Basque Country, Fac Sci, Dept Biochem & Mol Biol, Bilbao 48080, Spain
[2] Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada
关键词
ceramide-1-phosphate; PI3-kinase; protein kinase B; NF-kappa B; sphingomyelinase; apoptosis;
D O I
10.1016/j.febslet.2005.05.067
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:3744 / 3750
页数:7
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