PXD012671

PXD012671 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomics reveals the GSK3-PDX1 axis as a key pathogenic signaling node in diabetic islets
Description	Progressive decline of pancreatic beta cell function is central to the pathogenesis of type 2 diabetes. Protein phosphorylation regulates glucose-stimulated insulin secretion from beta cells, but how signaling networks are remodeled in diabetic islets in vivo remains unknown. Using high-sensitivity mass spectrometry-based proteomics we quantified 6,500 proteins and 13,000 phosphopeptides in islets of obese diabetic mice and matched controls, revealing drastic remodeling of key kinase hubs and signaling pathways. Integration with a literature-derived signaling network implicated GSK3 kinase in the control of the beta cell-specific transcription factor PDX1. Deep phosphoproteomic analysis of human islets chronically treated with high glucose demonstrated a conserved glucotoxicity-dependent role of GSK3 kinase in regulating insulin secretion. Remarkably, the ability of beta cells to secrete insulin in response to glucose was rescued almost completely by pharmacological inhibition of GSK3. Thus, our resource enables investigation of mechanisms and drug targets in type 2 diabetes.
HostingRepository	PRIDE
AnnounceDate	2019-03-15
AnnouncementXML	Submission_2019-04-03_07:35:17.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Natalie Krahmer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-12 03:40:04	ID requested
1	2019-03-15 09:29:00	announced
⏵ 2	2019-04-03 07:35:19	announced	Updated publication reference for PubMed record(s): 30879985.

Sacco F, Seelig A, Humphrey SJ, Krahmer N, Volta F, Reggio A, Marchetti P, Gerdes J, Mann M, Phosphoproteomics Reveals the GSK3-PDX1 Axis as a Key Pathogenic Signaling Node in Diabetic Islets. Cell Metab, 29(6):1422-1432.e3(2019) [pubmed]

submitter keyword: Diabetes, Islets, mass spectrometry, proteomics, phosphoproteomics, signalling networks, PDX1, GSK3, insulin secretion

Matthias Mann
contact affiliation	Max-Planck Institute of Biochemistry
contact email	mmann@biochem.mpg.de
lab head
Natalie Krahmer
contact affiliation	Max Planck of Biochemistry
contact email	krahmer@biochem.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/03/PXD012671

PRIDE project URI

• PRIDE
  1. PXD012671
     1. Label: PRIDE project
     2. Name: Phosphoproteomics reveals the GSK3-PDX1 axis as a key pathogenic signaling node in diabetic islets