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Cell Metab. 2015 Nov 3;22(5):922-35. doi: 10.1016/j.cmet.2015.09.001. Epub 2015 Oct 1.

Global Phosphoproteomic Analysis of Human Skeletal Muscle Reveals a Network of Exercise-Regulated Kinases and AMPK Substrates.

Author information

1
Charles Perkins Centre, School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia.
2
Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
3
Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; University of Copenhagen, August Krogh Centre, Department of Nutrition, Exercise and Sports, Copenhagen 2100, Denmark.
4
Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; Systems Biology Section, Epigenetics & Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
5
University of Copenhagen, August Krogh Centre, Department of Nutrition, Exercise and Sports, Copenhagen 2100, Denmark.
6
Systems Biology Section, Epigenetics & Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
7
Charles Perkins Centre, School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia; School of Medicine, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: david.james@sydney.edu.au.

Erratum in

  • Cell Metab. 2015 Nov 3;22(5):948.

Abstract

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.

Comment in

PMID:
26437602
PMCID:
PMC4635038
DOI:
10.1016/j.cmet.2015.09.001
[Indexed for MEDLINE]
Free PMC Article

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