Journal article

Phosphoproteomics reveals conserved exercise-stimulated signaling and AMPK regulation of store-operated calcium entry

Marin E Nelson, Benjamin L Parker, James G Burchfield, Nolan J Hoffman, Elise J Needham, Kristen C Cooke, Timur Naim, Lykke Sylow, Naomi XY Ling, Deanne Francis, Dougall M Norris, Rima Chaudhuri, Jonathan S Oakhill, Erik A Richter, Gordon S Lynch, Jacqueline Stockli, David E James

EMBO JOURNAL | WILEY | Published : 2019

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 i..

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Grants

Awarded by National Health and Medical Research Council (NHMRC)


Awarded by Danish Council for Independent Research/Medicine


Awarded by Novo Nordisk Foundation Excellence grant


Funding Acknowledgements

We are grateful to Fiona Colarossi for assistance with the animal ethics application and JOrgen Jensen for helpful discussions regarding skeletal muscle contraction models. We thank Dr. Anjana Rao (La Jolla Institute for Allergy and Immunology) for providing the STIM1 and ORAI1 plasmids. This work was supported by National Health and Medical Research Council (NHMRC) project grants GNT1120201 and GNT1086850 (D.E.J.), a grant from the Diabetes Australia Research Trust (D.E.J.), and a grant from the Danish Council for Independent Research/Medicine 6108-00203 (E.A.R.). D.E.J. is an NHMRC Senior Principal Research Fellow. B.L.P is supported by an NHMRC Early Career fellowship. Lykke Sylow is supported by a Novo Nordisk Foundation Excellence grant (32082). The contents of the published material are solely the responsibility of the individual authors and the Administering Institution and do not reflect the views of the NHMRC.