Personalized phosphoproteomics identifies functional signaling

Journal article


Needham, Elise J., Hingst, Janne R., Parker, Benjamin L., Morrison, Kaitlin R., Yang, Guang, Onslev, Johan, Kristensen, Jonas M., Højlund, Kurt, Ling, Naomi, Oakhill, Jonathan X. Y., Richter, Erik A., Kiens, Bente, Petersen, Janni, Pehmøller, Christian, James, David E., Wojtaszewski, Jørgen F. P. and Humphrey, Sean J.. (2022). Personalized phosphoproteomics identifies functional signaling. Nature Biotechnology. 40(4), pp. 576-584. https://doi.org/10.1038/s41587-021-01099-9
AuthorsNeedham, Elise J., Hingst, Janne R., Parker, Benjamin L., Morrison, Kaitlin R., Yang, Guang, Onslev, Johan, Kristensen, Jonas M., Højlund, Kurt, Ling, Naomi, Oakhill, Jonathan X. Y., Richter, Erik A., Kiens, Bente, Petersen, Janni, Pehmøller, Christian, James, David E., Wojtaszewski, Jørgen F. P. and Humphrey, Sean J.
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.

Year2022
JournalNature Biotechnology
Journal citation40 (4), pp. 576-584
PublisherNature Publishing Group
ISSN1087-0156
Digital Object Identifier (DOI)https://doi.org/10.1038/s41587-021-01099-9
PubMed ID34857927
Scopus EID2-s2.0-85120620185
Page range576-584
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All rights reserved
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Controlled
Output statusPublished
Publication dates
Online02 Dec 2021
Publication process dates
Accepted16 Sep 2021
Deposited18 Oct 2023
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