Phosphoproteomics of Acute Cell Stressors Targeting Exercise Signaling Networks Reveal Drug Interactions Regulating Protein Secretion
Elise J Needham, Sean J Humphrey, Kristen C Cooke, Daniel J Fazakerley, Xiaowen Duan, Benjamin L Parker, David E James
Cell Reports | CELL PRESS | Published : 2019
Exercise engages signaling networks to control the release of circulating factors beneficial to health. However, the nature of these networks remains undefined. Using high-throughput phosphoproteomics, we quantify 20,249 phosphorylation sites in skeletal muscle-like myotube cells and monitor their responses to a panel of cell stressors targeting aspects of exercise signaling in vivo. Integrating these in-depth phosphoproteomes with the phosphoproteome of acute aerobic exercise in human skeletal muscle suggests that co-administration of β-adrenergic and calcium agonists would activate complementary signaling relevant to this exercise context. The phosphoproteome of cells treated with this com..View full abstract
Awarded by NHMRC
We thank the members of the Metabolic Systems Biology group for constructive feedback and discussions and J. Cobcroft for funding support. This research was facilitated by access to Sydney Mass Spectrometry, a core research facility at the University of Sydney. Funding was provided through a grant from Diabetes Australia Research Program (D.E.J.) and an NHMRC project grant APP1122376 (B.L.P.). E.J.N. was supported by an Australian Government Research Training Program (RTP) Scholarship and the University of Sydney Val Street Scholarship. B.L.P. was an NHMRC Early Career fellow. S.J.H. is a Sydney University Postdoctoral Fellow, and D.E.J. is an NHMRC Senior Principal Research Fellow. The contents of the published material are solely the responsibility of the individual authors and do not reflect the view of NHMRC.