Personalized phosphoproteomics identifies functional signaling
| Autor: | Jonathan S. Oakhill, Janne R. Hingst, Elise J. Needham, Kurt Højlund, Erik A. Richter, Bente Kiens, Jonas M. Kristensen, Sean J. Humphrey, Jørgen F. P. Wojtaszewski, Naomi X.Y. Ling, Guang Yang, Kaitlin R. Morrison, Christian Pehmøller, Janni Petersen, Benjamin L. Parker, David E. James, Johan Onslev |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
biology
Signal Transduction/physiology Biomedical Engineering Phosphoproteomics AMPK Bioengineering Computational biology Applied Microbiology and Biotechnology Phenotype Insulin receptor Phosphoproteins/genetics biology.protein Molecular Medicine Phosphorylation Protein phosphorylation Signal transduction Proteomics/methods PI3K/AKT/mTOR pathway Biotechnology Biological Phenomena |
| Zdroj: | Needham, E J, Hingst, J R, Parker, B L, Morrison, K R, Yang, G, Onslev, J, Kristensen, J M, Højlund, K, Ling, N X Y, Oakhill, J S, Richter, E A, Kiens, B, Petersen, J, Pehmøller, C, James, D E, Wojtaszewski, J F P & Humphrey, S J 2022, ' Personalized phosphoproteomics identifies functional signaling ', Nature Biotechnology, vol. 40, no. 4, pp. 576-584 . https://doi.org/10.1038/s41587-021-01099-9 |
| DOI: | 10.1038/s41587-021-01099-9 |
| Popis: | 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. Functionally relevant phosphorylation sites are detected by integrating phosphoproteomic and phenotypic data. |
| Databáze: | OpenAIRE |
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