PXD032913-1

PXD032913 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomics reveals rewiring of the insulin signaling network and multi-nodal defects in insulin resistance
Description	Here we employed phosphoproteomics to delineate insulin signal transduction in adipocyte cells and adipose tissue. Across a range of insults triggering insulin resistance, we observed marked rewiring of the insulin signaling network. This included both attenuated insulin-responsive phosphorylation, and the emergence of phosphorylation uniquely insulin-regulated in insulin resistance. Identifying dysregulated phosphosites common to multiple insults revealed subnetworks containing novel regulators of insulin action, such as MARK2/3, and causal drivers of insulin resistance. The presence of several GSK3 substrates among these phosphosites led us to establish a pipeline for identifying context-specific kinase substrates. This revealed widespread dysregulation of GSK3 signaling. Pharmacological inhibition of GSK3 partially reversed insulin resistance in cells and tissue explants. These data highlight that insulin resistance is multi-nodal signaling defect that includes dysregulated GSK3 activity.
HostingRepository	PRIDE
AnnounceDate	2023-02-17
AnnouncementXML	Submission_2023-02-17_09:45:38.029.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	SeanHumphrey
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF; Orbitrap Exploris 480; Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-02 11:42:32	ID requested
⏵ 1	2023-02-17 09:45:38	announced
2	2023-11-14 08:55:36	announced	2023-11-14: Updated project metadata.

submitter keyword: post-translational modification, adipocyte, mass spectrometry, fat, phosphoproteomics, GSK3, tissue, proteomics, adipose, signal transduction, phosphorylation, insulin signalling,insulin resistance

SeanHumphrey
contact affiliation	The University of Sydney, Australia
contact email	sean.j.humphrey@gmail.com
lab head
SeanHumphrey
contact affiliation	Murdoch Children's Research Institute
contact email	sean.j.humphrey@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD032913
     1. Label: PRIDE project
     2. Name: Phosphoproteomics reveals rewiring of the insulin signaling network and multi-nodal defects in insulin resistance