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
Authors | 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. |
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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. |
Year | 2022 |
Journal | Nature Biotechnology |
Journal citation | 40 (4), pp. 576-584 |
Publisher | Nature Publishing Group |
ISSN | 1087-0156 |
Digital Object Identifier (DOI) | https://doi.org/10.1038/s41587-021-01099-9 |
PubMed ID | 34857927 |
Scopus EID | 2-s2.0-85120620185 |
Page range | 576-584 |
Publisher's version | License All rights reserved File Access Level Controlled |
Output status | Published |
Publication dates | |
Online | 02 Dec 2021 |
Publication process dates | |
Accepted | 16 Sep 2021 |
Deposited | 18 Oct 2023 |
https://acuresearchbank.acu.edu.au/item/8zw4z/personalized-phosphoproteomics-identifies-functional-signaling
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