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Title: Microtubule dynamics regulates Akt signaling via dynactin p150
Authors: Hakryul Jo
Fabien Loison
Hongbo R. Luo
Yale University
Children's Hospital Boston
Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 1-Jan-2014
Citation: Cellular Signalling. Vol.26, No.8 (2014), 1707-1716
Abstract: Following activation at the plasma membrane, Akt is subsequently deactivated in the cytoplasm.Although activation and deactivation of Akt must sometimes be separated in order to elicit and control cellular responses, the exact details of the spatiotemporal organization of Akt signaling are incompletely understood. Here we show that microtubule dynamics specifically modulate the deactivation phase of Akt signaling. Localization of Akt to microtubules sustains its activity, while disruption of microtubules attenuates Akt signaling independent of its initial activation.Conversely, stabilization of microtubules elevates Akt signaling both in vitro and in muscle tissues in vivo. Localization of Akt to microtubules is mediated by the microtubule binding protein dynactin p150, which is shown to be a direct target of Akt. Finally, microtubule disruption-induced Akt deactivation contributes to delayed cell cycle progression and accelerated cell death. Taken together, we revealed that, after initiation, the overall intensity and duration of oncogenic Akt signaling are determined by microtubule dynamics, a mechanism that could be exploited for therapeutic purposes. © 2014 Elsevier Inc.
ISSN: 18733913
Appears in Collections:Scopus 2011-2015

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