PXD015733

PXD015733 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Quantitative In Vivo Proteomics of Metformin Response in Liver Reveals AMPK-Dependent and -Independent Signaling Networks
Description	Metformin is the front-line treatment for type 2 diabetes worldwide. It acts via effects on glucose and lipid metabolism in metabolic tissues, leading to enhanced insulin sensitivity. Despite significant effort, the molecular basis for metformin response remains poorly understood, with a limited number of specific biochemical pathways studied to date. To broaden our understanding of hepatic metformin response, we combine phospho-protein enrichment in tissue from genetically engineered mice with a quantitative proteomics platform to enable the discovery and quantification of basophilic kinase substrates in-vivo. We define proteins that binding to 14-3-3 are acutely regulated by metformin treatment and/or loss of the serine/threonine kinase, LKB1. Inducible binding of 250 proteins following metformin treatment is observed, 44% LKB1-dependent. Beyond AMPK, metformin activates Protein Kinase D and MAPKAPK2 in an LKB1-independent manner, revealing additional kinases that may mediate aspects of metformin response. Deeper analysis uncovered substrates of AMPK in endocytosis and calcium homeostasis.
HostingRepository	MassIVE
AnnounceDate	2020-01-08
AnnouncementXML	Submission_2020-01-08_18:28:00.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Salvador Martínez de Bartolomé
SpeciesList	scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationList	Carbamidomethyl
Instrument	LTQ Orbitrap Elite; LTQ Orbitrap Velos

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2019-10-07 15:23:28	ID requested
⏵ 1	2020-01-08 18:28:01	announced

Publication List

Stein BD, Calzolari D, Hellberg K, Hu YS, He L, Hung CM, Toyama EQ, Ross DS, Lillemeier BF, Cantley LC, Yates JR, Shaw RJ, Vivo Proteomics of Metformin Response in Liver Reveals AMPK-Dependent and -Independent Signaling Networks. Cell Rep, 29(10):3331-3348.e7(2019) [pubmed]

Stein BD, Calzolari D, Hellberg K, Hu YS, He L, Hung CM, Toyama EQ, Ross DS, Lillemeier BF, Cantley LC, Yates JR, Shaw RJ, Vivo Proteomics of Metformin Response in Liver Reveals AMPK-Dependent and -Independent Signaling Networks. Cell Rep, 29(10):3331-3348.e7(2019) [pubmed]

Keyword List

submitter keyword: metformin, diabetes, cancer, aging, AMPK, LKB1, liver, kinase, 14-3-3, SILAM, proteomics, PKD, MK2, STIM1, STIM2, calcium

submitter keyword: metformin, diabetes, cancer, aging, AMPK, LKB1, liver, kinase, 14-3-3, SILAM, proteomics, PKD, MK2, STIM1, STIM2, calcium

Contact List

John R. Yates III
contact affiliation	The Scripps Research Institute
contact email	jyates@scripps.edu
lab head
Salvador Martínez de Bartolomé
contact affiliation	The Scripps Research Institute
contact email	salvador@scripps.edu
dataset submitter

Full Dataset Link List

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MassIVE dataset URI

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://massive.ucsd.edu/MSV000084429/