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Phosphoproteomics reveals conserved exercise-stimulated signaling and AMPK regulation of store-operated calcium entry
Nelson, Marin E. Parker, Benjamin L. Burchfield, James G. Hoffman, Nolan J. Needham, Elise J. Cooke, Kristen C. Naim, Timur Sylow, Lykke Ling, Naomi X. Y. Francis, Deanne
Nelson, Marin E.
Parker, Benjamin L.
Burchfield, James G.
Hoffman, Nolan J.
Needham, Elise J.
Cooke, Kristen C.
Naim, Timur
Sylow, Lykke
Ling, Naomi X. Y.
Francis, Deanne
Author
Abstract
Exercise stimulates cellular and physiological adaptations that are associated with widespread health benefits. To uncover conserved protein phosphorylation events underlying this adaptive response, we performed mass spectrometry‐based phosphoproteomic analyses of skeletal muscle from two widely used rodent models: treadmill running in mice and in situ muscle contraction in rats. We overlaid these phosphoproteomic signatures with cycling in humans to identify common cross‐species phosphosite responses, as well as unique model‐specific regulation. We identified > 22,000 phosphosites, revealing orthologous protein phosphorylation and overlapping signaling pathways regulated by exercise. This included two conserved phosphosites on stromal interaction molecule 1 (STIM1), which we validate as AMPK substrates. Furthermore, we demonstrate that AMPK‐mediated phosphorylation of STIM1 negatively regulates store‐operated calcium entry, and this is beneficial for exercise in Drosophila. This integrated cross‐species resource of exercise‐regulated signaling in human, mouse, and rat skeletal muscle has uncovered conserved networks and unraveled crosstalk between AMPK and intracellular calcium flux.
Keywords
AMPK, calcium, exercise, phosphorylation, STIM1
Date
2019
Type
Journal article
Journal
The EMBO Journal
Book
Volume
38
Issue
24
Page Range
1-20
Article Number
ACU Department
Centre for Exercise and Nutrition
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
License
File Access
Controlled