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

Authors :
Su Z
Burchfield JG
Yang P
Humphrey SJ
Yang G
Francis D
Yasmin S
Shin SY
Norris DM
Kearney AL
Astore MA
Scavuzzo J
Fisher-Wellman KH
Wang QP
Parker BL
Neely GG
Vafaee F
Chiu J
Yeo R
Hogg PJ
Fazakerley DJ
Nguyen LK
Kuyucak S
James DE
Source :
Nature communications [Nat Commun] 2019 Dec 02; Vol. 10 (1), pp. 5486. Date of Electronic Publication: 2019 Dec 02.
Publication Year :
2019

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 PIP <subscript>3</subscript> 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.

Details

Language :
English
ISSN :
2041-1723
Volume :
10
Issue :
1
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
31792197
Full Text :
https://doi.org/10.1038/s41467-019-13114-4