PXD001032

PXD001032 is an original dataset announced via ProteomeXchange.

Title	SIK2 phosphorylation in response to glucagon or insulin in murine hepatocytes
Description	The phosphorylation state of human HA-tagged-SIK2, adenovirally introduced in murine hepatocytes (C57/BL/6 strain) was analysed in unstimulated and in response to glucagon- or insulin- treated conditions. Background:- LKB1 is a master kinase that regulates metabolism and growth through AMPK and 12 other closely-related kinases. Liver-specific ablation of LKB1 causes increased glucose production in hepatocytes in vitro and hyperglycaemia in fasting mice in vivo. The salt-inducible kinases (SIK1, 2 and 3), members of the AMPK-related kinase family, play a key role as gluconeogenic suppressor downstream of LKB1 in the liver. A selective SIK inhibitor (HG-9-91-01) promotes dephosphorylation of transcriptional co-activators CRTC2/3 resulting in enhanced gluconeogenic gene expression and glucose production in hepatocytes, an effect that is abolished when an HG-9-91-01-insensitive-mutant-SIK is introduced or LKB1 is ablated. Although SIK2 was proposed as a key regulator of insulin-mediated suppression of gluconeogenesis, we provide genetic evidence that liver-specific ablation of SIK2 alone has no effect on gluconeogenesis and insulin does not modulate SIK2 phosphorylation/activity. Collectively, we demonstrate that the LKB1-SIK pathway functions as a key gluconeogenic gatekeeper in the liver.
HostingRepository	PRIDE
AnnounceDate	2014-10-23
AnnouncementXML	Submission_2014-10-23_03:56:10.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Campbell
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap; Q TRAP

Revision	Datetime	Status	ChangeLog Entry
0	2014-06-04 00:25:48	ID requested
1	2014-08-08 06:03:43	announced
⏵ 2	2014-10-23 03:56:12	announced	Updated project metadata.

Patel K, Foretz M, Marion A, Campbell DG, Gourlay R, Boudaba N, Tournier E, Titchenell P, Peggie M, Deak M, Wan M, Kaestner KH, G, ö, ransson O, Viollet B, Gray NS, Birnbaum MJ, Sutherland C, Sakamoto K, The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver. Nat Commun, 5():4535(2014) [pubmed]

curator keyword: Biomedical, Biological

submitter keyword: SIK2, hepatocytes, AMPK, AMPK-related kinase, LKB1, insulin, glucagon, hepatic glucose production, cAMP, CREB, CRTC2

Kei Sakamoto
contact affiliation	Head of Diabetes Nestlé Institute of Health Sciences SA Campus EPFL Quartier de l'innovation, bâtiment G 1015 Lausanne (Switzerland)
contact email	Kei.Sakamoto@rd.nestle.com
lab head
David Campbell
contact affiliation	Dundee University, UK
contact email	d.g.campbell@dundee.ac.uk
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/2014/08/PXD001032

PRIDE project URI

• PRIDE
  1. PXD001032
     1. Label: PRIDE project
     2. Name: SIK2 phosphorylation in response to glucagon or insulin in murine hepatocytes