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Global redox proteome and phosphoproteome analysis reveals redox switch in Akt

Author

Listed:
  • Zhiduan Su

    (The University of Sydney
    The University of Sydney)

  • James G. Burchfield

    (The University of Sydney
    The University of Sydney)

  • Pengyi Yang

    (The University of Sydney
    The University of Sydney)

  • Sean J. Humphrey

    (The University of Sydney
    The University of Sydney)

  • Guang Yang

    (The University of Sydney
    The University of Sydney)

  • Deanne Francis

    (The University of Sydney
    The University of Sydney)

  • Sabina Yasmin

    (The University of Sydney)

  • Sung-Young Shin

    (Monash University
    Monash University)

  • Dougall M. Norris

    (The University of Sydney
    The University of Sydney)

  • Alison L. Kearney

    (The University of Sydney
    The University of Sydney)

  • Miro A. Astore

    (The University of Sydney)

  • Jonathan Scavuzzo

    (The University of Sydney
    The University of Sydney)

  • Kelsey H. Fisher-Wellman

    (East Carolina University
    East Carolina University)

  • Qiao-Ping Wang

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Benjamin L. Parker

    (The University of Sydney
    The University of Sydney)

  • G. Gregory Neely

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

  • Fatemeh Vafaee

    (The University of Sydney
    The University of Sydney)

  • Joyce Chiu

    (The Centenary Institute
    The University of Sydney)

  • Reichelle Yeo

    (The Centenary Institute
    The University of Sydney)

  • Philip J. Hogg

    (The Centenary Institute
    The University of Sydney)

  • Daniel J. Fazakerley

    (The University of Sydney
    The University of Sydney)

  • Lan K. Nguyen

    (Monash University
    Monash University)

  • Serdar Kuyucak

    (The University of Sydney)

  • David E. James

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

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.

Suggested Citation

  • 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 Sc, 2019. "Global redox proteome and phosphoproteome analysis reveals redox switch in Akt," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13114-4
    DOI: 10.1038/s41467-019-13114-4
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    Citations

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    Cited by:

    1. Renan B. Ferreira & Ling Fu & Youngeun Jung & Jing Yang & Kate S. Carroll, 2022. "Reaction-based fluorogenic probes for detecting protein cysteine oxidation in living cells," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Wenping Zhou & Wenxue Li & Shisheng Wang & Barbora Salovska & Zhenyi Hu & Bo Tao & Yi Di & Ujwal Punyamurtula & Benjamin E. Turk & William C. Sessa & Yansheng Liu, 2023. "An optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Daniel J. Fazakerley & Julian van Gerwen & Kristen C. Cooke & Xiaowen Duan & Elise J. Needham & Alexis Díaz-Vegas & Søren Madsen & Dougall M. Norris & Amber S. Shun-Shion & James R. Krycer & James G. , 2023. "Phosphoproteomics reveals rewiring of the insulin signaling network and multi-nodal defects in insulin resistance," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Joan Pous & Blazej Baginski & Pau Martin-Malpartida & Lorena González & Margherita Scarpa & Eric Aragon & Lidia Ruiz & Rebeca A. Mees & Javier Iglesias-Fernández & Modesto Orozco & Angel R. Nebreda & , 2023. "Structural basis of a redox-dependent conformational switch that regulates the stress kinase p38α," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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