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Ceramide‐1‐phosphate promotes cell survival through activation of the phosphatidylinositol 3‐kinase/protein kinase B pathway
Author(s) -
Gómez-Muñoz Antonio,
Kong Jennifer Y.,
Parhar Kuljit,
Wang Shih Wei,
Gangoiti Patricia,
González Mónica,
Eivemark Sharlene,
Salh Bill,
Duronio Vincent,
Steinbrecher Urs P.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.05.067
Subject(s) - ceramide , phosphatidylinositol , kinase , microbiology and biotechnology , protein kinase b , lipid signaling , signal transduction , phosphorylation , biology , cell growth , protein kinase a , apoptosis , chemistry , biochemistry , enzyme
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.