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Global redox proteome and phosphoproteome analysis reveals redox switch in Akt.
- 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.
- Subjects :
- Adipocytes metabolism
Animals
Cysteine genetics
Cysteine metabolism
Humans
Mice
Oxidation-Reduction
Oxidative Stress
Phosphoproteins chemistry
Phosphoproteins genetics
Phosphorylation
Protein Domains
Proteome chemistry
Proteome genetics
Proteome metabolism
Proteomics
Proto-Oncogene Proteins c-akt chemistry
Proto-Oncogene Proteins c-akt genetics
Signal Transduction
TOR Serine-Threonine Kinases genetics
TOR Serine-Threonine Kinases metabolism
Phosphoproteins metabolism
Proto-Oncogene Proteins c-akt metabolism
Subjects
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