Global redox proteome and phosphoproteome analysis reveals redox switch in Akt

Zhiduan Su, James G. Burchfield, Pengyi Yang, Sean J. Humphrey, Guang Yang, Deanne Francis, Sabina Yasmin, Sung-Young Shin, Dougall M. Norris, Alison L. Kearney, Miro A. Astore, Jonathan Scavuzzo, Kelsey H. Fisher-Wellman, Qiao-Ping Wang, Benjamin L. Parker, G. Gregory Neely, Fatemeh Vafaee, Joyce Chiu, Reichelle Yeo, Philip J. Hogg, Daniel J. Fazakerley, Lan K. Nguyen, Serdar Kuyucak and David E. James ()
Additional contact information
Zhiduan Su: The University of Sydney
James G. Burchfield: The University of Sydney
Pengyi Yang: The University of Sydney
Sean J. Humphrey: The University of Sydney
Guang Yang: The University of Sydney
Deanne Francis: The University of Sydney
Sabina Yasmin: The University of Sydney
Sung-Young Shin: Monash University
Dougall M. Norris: The University of Sydney
Alison L. Kearney: The University of Sydney
Miro A. Astore: The University of Sydney
Jonathan Scavuzzo: The University of Sydney
Kelsey H. Fisher-Wellman: East Carolina University
Qiao-Ping Wang: The University of Sydney
Benjamin L. Parker: The University of Sydney
G. Gregory Neely: The University of Sydney
Fatemeh Vafaee: The University of Sydney
Joyce Chiu: The Centenary Institute
Reichelle Yeo: The Centenary Institute
Philip J. Hogg: The Centenary Institute
Daniel J. Fazakerley: The University of Sydney
Lan K. Nguyen: Monash University
Serdar Kuyucak: The University of Sydney
David E. James: The University of Sydney

Nature Communications, 2019, vol. 10, issue 1, 1-18

Abstract: 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.

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13114-4

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DOI: 10.1038/s41467-019-13114-4

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