PXD010212

PXD010212 is an original dataset announced via ProteomeXchange.

Title	Proteomic and phosphoproteomic analysis of PKCe KO
Description	Activation of protein kinase C epsilon (PKCε) in the liver has been widely associated with hepatic insulin resistance. PKCε is proposed to inhibit insulin signalling through phosphorylation of the insulin receptor. We have tested this directly by breeding PKCε floxed mice with mice expressing Cre recombinase under the control of the cytomegalovirus, albumin or adiponectin promoters to generate global, liver- and adipose tissue-specific PKCε knockout (KO) mice. Global deletion of PKCε recapitulated the benefits for diet-induced glucose intolerance that we previously described using conventional PKCε KO mice. However, we did not detect PKCε-dependent alterations in hepatic insulin receptor phosphorylation. Furthermore, liver-specific KO mice were not protected against diet-induced glucose intolerance or insulin resistance determined by euglycemic clamp. In contrast, adipose tissue-specific KO mice exhibited improved glucose tolerance and mildly increased hepatic triglyceride storage, but no change in liver insulin sensitivity. Phosphoproteomic analysis of insulin signalling in PKCε KO adipocytes revealed no defect in the canonical INSR/AKT/mTOR pathways. However, PKCε KO resulted in changes in phosphorylation of several proteins associated with the endosome and cell junctions suggesting regulation in secretory pathways and a potential role of PKCε in endocrine function. Indeed, RNA-seq analysis revealed adipose-tissue PKCε-dependent changes in the hepatic expression of several genes linked to glucose homeostasis and hepatic lipid metabolism. The primary effect of PKCε on glucose homeostasis is therefore not exerted directly in the liver as currently assumed. However, PKCε in adipose tissue modulates glucose tolerance and is involved in crosstalk with the liver that affects gene expression and lipid accumulation.
HostingRepository	PRIDE
AnnounceDate	2018-10-04
AnnouncementXML	Submission_2018-10-04_08:55:35.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Benjamin Parker
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-06-25 03:28:57	ID requested
⏵ 1	2018-10-04 08:55:36	announced

Dataset with its publication pending

curator keyword: Biological

submitter keyword: PKCepsilon, adipocyte

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. PXD010212
     1. Label: PRIDE project
     2. Name: Proteomic and phosphoproteomic analysis of PKCe KO