Inhibition of the anti-apoptotic PI(3)K/Akt/Bad pathway by stress
Open Access
- 1 July 1998
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 12 (13) , 1941-1946
- https://doi.org/10.1101/gad.12.13.1941
Abstract
The initiation of apoptosis often transpires in the presence of agents that regulate cell survival. This study evaluated the effects of stress-induced ceramide on the anti-apoptotic activity of the phosphoinositide-3 kinase [PI(3)K] pathway. PI(3)K activity is directly down-regulated by stress-induced ceramide in a dose-dependent manner with rapid kinetics and high specificity. Ceramide inhibition of PI(3)K is dependent on acid–sphingomyelinase. Down-regulation of PI(3)K by ceramide results in inhibition of the kinase Akt and decreased phosphorylation of the death effector Bad. Thus, ceramide levels could act as a general apoptotic rheostat controlling cell survival by regulating PI(3)K anti-apoptotic effector mechanisms.Keywords
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