Global redox proteome and phosphoproteome analysis reveals redox switch in Akt

Global redox proteome and phosphoproteome analysis reveals redox switch in Akt.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1038/s41467-019-13114-4
Journal or Publication Title: Nature Communications
Volume: 10
Number: 1
Date: 2019
Divisions: ACRF Centenary Cancer Research Centre
Depositing User: General Admin
Identification Number: 10.1038/s41467-019-13114-4
ISSN: 2041-1723
Date Deposited: 17 Dec 2020 03:56
Abstract:

Protein oxidation sits at the intersection of multiple signalling pathways, yet the magnitude and extent of crosstalk between oxidation and other post-translational modifications remains unclear. Here, we delineate global changes in adipocyte signalling networks following acute oxidative stress and reveal considerable crosstalk between cysteine oxidation and phosphorylation-based signalling. Oxidation of key regulatory kinases, including Akt, mTOR and AMPK influences the fidelity rather than their absolute activation state, highlighting an unappreciated interplay between these modifications. Mechanistic analysis of the redox regulation of Akt identified two cysteine residues in the pleckstrin homology domain (C60 and C77) to be reversibly oxidized. Oxidation at these sites affected Akt recruitment to the plasma membrane by stabilizing the PIP3 binding pocket. Our data provide insights into the interplay between oxidative stress-derived redox signalling and protein phosphorylation networks and serve as a resource for understanding the contribution of cellular oxidation to a range of diseases.

Creators:
Creators
Email
Su, Zhiduan
UNSPECIFIED
Burchfield, James G.
UNSPECIFIED
Yang, Pengyi
UNSPECIFIED
Humphrey, Sean J.
UNSPECIFIED
Yang, Guang
UNSPECIFIED
Francis, Deanne
UNSPECIFIED
Yasmin, Sabina
UNSPECIFIED
Shin, Sung-Young
UNSPECIFIED
Norris, Dougall M.
UNSPECIFIED
Kearney, Alison L.
UNSPECIFIED
Astore, Miro A.
UNSPECIFIED
Scavuzzo, Jonathan
UNSPECIFIED
Fisher-Wellman, Kelsey H.
UNSPECIFIED
Wang, Qiao-Ping
UNSPECIFIED
Parker, Benjamin L.
UNSPECIFIED
Neely, G. Gregory
UNSPECIFIED
Vafaee, Fatemeh
UNSPECIFIED
Chiu, Joyce
UNSPECIFIED
Yeo, Reichelle
UNSPECIFIED
Hogg, Philip J.
UNSPECIFIED
Fazakerley, Daniel J.
UNSPECIFIED
Nguyen, Lan K.
UNSPECIFIED
Kuyucak, Serdar
UNSPECIFIED
James, David E.
UNSPECIFIED
Last Modified: 17 Dec 2020 03:56
URI: https://eprints.centenary.org.au/id/eprint/128

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