Affiliation:
1. Department of Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607
Abstract
ABSTRACT
Growth factors signaling through the phosphoinositide 3-kinase/Akt pathway promote cell survival. The mechanism by which the serine/threonine kinase Akt prevents cell death remains unclear. We have previously shown that Akt inhibits the activity of DEVD-targeted caspases without changing the steady-state levels of Bcl-2 and Bcl-x
L
. Here we show that Akt inhibits apoptosis and the processing of procaspases to their active forms by delaying mitochondrial changes in a caspase-independent manner. Akt activation is sufficient to inhibit the release of cytochrome
c
from mitochondria and the alterations in the inner mitochondrial membrane potential. However, Akt cannot inhibit apoptosis induced by microinjection of cytochrome
c
. We also demonstrated that Akt inhibits apoptosis and cytochrome
c
release induced by several proapoptotic Bcl-2 family members. Taken together, our results show that Akt promotes cell survival by intervening in the apoptosis cascade before cytochrome
c
release and caspase activation via a mechanism that is distinct from Bad phosphorylation.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
490 articles.
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