Effects of ethanol on conformational changes of Akt studied by chemical cross-linking, mass spectrometry, and (18)O labeling.

ABSTRACT: Although PI3K/Akt signaling that regulates neuronal survival has been implicated in the deleterious effects of ethanol on the central nervous system, underlying molecular mechanisms have not been fully elucidated. Akt-membrane interaction is a prerequisite step for Akt activation since it induces interdomain conformational changes to an open conformer that allows Akt phosphorylation by upstream kinases. In this study, we investigated the effect of ethanol on Akt activation by quantitatively probing Akt conformation using chemical cross-linking, (18)O labeling and mass spectrometry. We found that ethanol at pharmacologically relevant concentrations (20 or 170 mM) directly interacts with Akt and alters the local pleckstrin homology domain configuration near the PIP(3)-binding site. We also f

SUBMITTER: Huang BX 

PROVIDER: S-EPMC3475205 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature