Back to Search
Start Over
Phosphoproteomics of Acute Cell Stressors Targeting Exercise Signaling Networks Reveal Drug Interactions Regulating Protein Secretion
- Source :
- Cell Reports, Vol 29, Iss 6, Pp 1524-1538.e6 (2019)
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- Summary: 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 combination reveals a surprising divergence in signaling from the individual treatments. Remarkably, only the combination treatment promotes multisite phosphorylation of SERBP1, a regulator of Serpine1 mRNA stability, a pro-fibrotic secreted protein. Secretome analysis reveals that the combined treatments decrease secretion of SERPINE1 and other deleterious factors. This study provides a framework for dissecting phosphorylation-based signaling relevant to acute exercise. : Needham et al. measure phosphoproteomes of acute cell stressors targeting different aspects of exercise signaling. This reveals treatment actions and creates a resource of treatments that regulate phosphosites regulated in acute aerobic exercise in human skeletal muscle. Combining isoproterenol and thapsigargin causes extensive interactions within the phosphoproteome and secretome. Keywords: phosphoproteomics, proteomics, exercise, myotubes, EasyPhos, signal transduction, mass spectrometry, berberine, AMPK, secretome
- Subjects :
- 0301 basic medicine
Proteome
Aripiprazole
Context (language use)
Biology
Proteomics
Mass Spectrometry
General Biochemistry, Genetics and Molecular Biology
Mice
03 medical and health sciences
0302 clinical medicine
AMP-Activated Protein Kinase Kinases
Stress, Physiological
Plasminogen Activator Inhibitor 1
Animals
Humans
Aerobic exercise
Drug Interactions
Secretion
Phosphorylation
Muscle, Skeletal
Exercise
lcsh:QH301-705.5
Myogenesis
Isoproterenol
Phosphoproteomics
RNA-Binding Proteins
Adrenergic beta-Agonists
Phosphoproteins
Rats
Cell biology
030104 developmental biology
lcsh:Biology (General)
Protein Translocation Systems
Thapsigargin
Calcium
Signal transduction
Protein Kinases
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 29
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....72e46591dab05b20de9c5336f8a7679d