Personalized phosphoproteomics identifies functional signaling

Elise J Needham, Janne Rasmuss Hingst, Benjamin L Parker, Kaitlin R Morrison, Guang Yang, Johan Dejgaard Onslev, Jonas Møller Kristensen, Kurt Højlund, Naomi X Y Ling, Jonathan S Oakhill, Erik A. Richter, Bente Kiens, Janni Petersen, Christian Pehmøller, David E James*, Jørgen Wojtaszewski*, Sean J Humphrey*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

45 Citationer (Scopus)

Abstract

Protein phosphorylation dynamically integrates environmental and cellular information to control biological processes. Identifying functional phosphorylation amongst the thousands of phosphosites regulated by a perturbation at a global scale is a major challenge. Here we introduce 'personalized phosphoproteomics', a combination of experimental and computational analyses to link signaling with biological function by utilizing human phenotypic variance. We measure individual subject phosphoproteome responses to interventions with corresponding phenotypes measured in parallel. Applying this approach to investigate how exercise potentiates insulin signaling in human skeletal muscle, we identify both known and previously unidentified phosphosites on proteins involved in glucose metabolism. This includes a cooperative relationship between mTOR and AMPK whereby the former directly phosphorylates the latter on S377, for which we find a role in metabolic regulation. These results establish personalized phosphoproteomics as a general approach for investigating the signal transduction underlying complex biology.

OriginalsprogEngelsk
TidsskriftNature Biotechnology
Vol/bind40
Udgave nummer4
Sider (fra-til)576-584
Antal sider9
ISSN1087-0156
DOI
StatusUdgivet - 2022

Bibliografisk note

CURIS 2022 NEXS 110

© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.

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