The DOI matches its Crossref record; 49 of the 50 references it cites were found in a registry or an index.
Global Phosphoproteomic Analysis of Human Skeletal Muscle Reveals a Network of Exercise-Regulated Kinases and AMPK Substrates
Open accessAbstract
Exercise is essential in regulating energy metabolism and whole-body insulin sensitivity. To explore the exercise signaling network, we undertook a global analysis of protein phosphorylation in human skeletal muscle biopsies from untrained healthy males before and after a single high-intensity exercise bout, revealing 1,004 unique exercise-regulated phosphosites on 562 proteins. These included substrates of known exercise-regulated kinases (AMPK, PKA, CaMK, MAPK, mTOR), yet the majority of kinases and substrate phosphosites have not previously been implicated in exercise signaling. Given the importance of AMPK in exercise-regulated metabolism, we performed a targeted in vitro AMPK screen and employed machine learning to predict exercise-regulated AMPK substrates. We validated eight predicted AMPK substrates, including AKAP1, using targeted phosphoproteomics. Functional characterization revealed an undescribed role for AMPK-dependent phosphorylation of AKAP1 in mitochondrial respiration. These data expose the unexplored complexity of acute exercise signaling and provide insights into the role of AMPK in mitochondrial biochemistry.
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“Moreover, the phosphorylation of human BAG3 on Thr285 and Ser 289 decreases in response to endurance exercise (61).”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [61]
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Skyline: an open source document editor for creating and analyzing targeted proteomics experiments
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AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
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Exercise Metabolism and the Molecular Regulation of Skeletal Muscle Adaptation
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Metadata
- Authors
- Hoffman, N. J., Parker, B. L., Chaudhuri, R., Fisher-Wellman, K. H., Kleinert, M., Humphrey, S. J., Yang, P., Holliday, M., Trefely, S., Fazakerley, D. J., Stöckli, J., Burchfield, J. G., Jensen, T. E., Jothi, R., Kiens, B., Wojtaszewski, J. F. P., Richter, E. A., & James, D. E.
- Affiliations
- The University of Sydney (AU)
- University of Copenhagen (DK)
- Garvan Institute of Medical Research (AU)
- National Institutes of Health (US)
- Corresponding author
- James, David E.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 22
- Issue
- 5
- Pages
- 922-935
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4635038
- OpenAlex
- W1839260472
- Cited by
- 426
- References
- 50
- Citations by year
- 2026: 27 · 2025: 38 · 2024: 45 · 2023: 37 · 2022: 47 · 2021: 46 · 2020: 45 · 2019: 50 · 2018: 32 · 2017: 30 · 2016: 25 · 2015: 4
- FWCI
- 13.18
- Type
- journal article
- Language
- en
- Update notices
- erratum (2015-11-03)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- Funders
- Novo Nordisk Fonden (NNF15OC0015182, NNF14OC0012009, NNF14OC0012319)
- National Institutes of Health
- National Institute of Environmental Health Sciences (ZIAES102625)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Keywords
- skeletal muscle, protein phosphorylation, AKAP1, mitochondrial respiration, high-intensity exercise, phosphosites, kinase substrates, energy metabolism, insulin sensitivity, phosphoproteomics
- MeSH terms
- Machine Learning, Adult, Energy Metabolism, Humans, Male, Mitochondria, Phosphoproteins, Phosphorylation, Physical Conditioning, Animal, Substrate Specificity, Signal Transduction, Exercise, Muscle, Skeletal, A Kinase Anchor Proteins, AMP-Activated Protein Kinases
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