PXD014322

PXD014322 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomic screening of exercise-like treatments reveals drug interactions regulating protein secretion
Description	Exercise triggers skeletal muscle signalling pathways that modulate the release of circulating factors to cause systemic health benefits. Understanding these mechanisms could lead to better strategies for treating cardiometabolic diseases. We previously showed that acute exercise induces >1000 changes in protein phosphorylation in human muscle. Here we employed a strategy to deconvolute this network by analysing phosphoproteomes of rat L6 myotubes treated with small molecules that mimic different aspects of exercise signalling. Bioinformatics suggested that combining β-adrenergic and calcium agonists would yield a phosphoproteome most closely resembling exercise. Experimental analysis supported this but also revealed a surprising divergence in signalling from that observed with either drug alone. Dual stimulation promoted multisite phosphorylation of SERBP1, a regulator of Serpine1 mRNA stability, a pro-thrombotic fibrotic secreted protein. Secretomic analysis of L6 myotubes treated with β-adrenergic and calcium agonists revealed a significant decrease in SERPINE1 secretion and other deleterious secretory factors. This provides a novel approach to dissect the beneficial effects of exercise and demonstrates an underappreciated effect of exercise to reduce the circulating levels of certain factors, providing new insights into exercise benefits and their therapeutic potential.
HostingRepository	PRIDE
AnnounceDate	2019-09-26
AnnouncementXML	Submission_2019-11-11_00:34:39.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Benjamin Parker
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-06-20 03:20:52	ID requested
1	2019-09-25 21:33:39	announced
⏵ 2	2019-11-11 00:34:41	announced	2019-11-11: Updated publication reference for PubMed record(s): 31693893.

Needham EJ, Humphrey SJ, Cooke KC, Fazakerley DJ, Duan X, Parker BL, James DE, Phosphoproteomics of Acute Cell Stressors Targeting Exercise Signaling Networks Reveal Drug Interactions Regulating Protein Secretion. Cell Rep, 29(6):1524-1538.e6(2019) [pubmed]

submitter keyword: phosphoproteomics, myotubes, exercise

Benjamin Parker
contact affiliation	the University of Sydney
contact email	benjamin.parker@sydney.edu.au
lab head
Benjamin Parker
contact affiliation	The University of Sydney
contact email	benjamin.parker@sydney.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014322
     1. Label: PRIDE project
     2. Name: Phosphoproteomic screening of exercise-like treatments reveals drug interactions regulating protein secretion