Phosphoproteomics reveals conserved exercise-stimulated signaling and AMPK regulation of store-operated calcium entry.
EMBO J
; 38(24): e102578, 2019 12 16.
Article
en En
| MEDLINE
| ID: mdl-31381180
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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Canales de Calcio
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Calcio
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Proteómica
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Proteínas Quinasas Activadas por AMP
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Molécula de Interacción Estromal 1
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
EMBO J
Año:
2019
Tipo del documento:
Article