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 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.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Gómez-Muñoz A,Kong JY,Parhar K,Wang SW,Gangoiti P,González M,Eivemark S,Salh B,Duronio V,Steinbrecher UPdoi
10.1016/j.febslet.2005.05.067keywords:
subject
Has Abstractpub_date
2005-07-04 00:00:00pages
3744-50issue
17eissn
0014-5793issn
1873-3468pii
S0014-5793(05)00693-9journal_volume
579pub_type
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