PXD015245

PXD015245 is an original dataset announced via ProteomeXchange.

Title	Time-resolved Phosphoproteomic Analysis Elucidates Hepatic 11,12-Epoxyeicosatrienoic Acid Signaling Pathways
Description	Epoxyeicosatrienoic acids (EETs) are potent lipid mediators with well-established effects in vascular tissues. Recent studies indicated an emerging role of these eicosanoids in metabolic diseases and the EET signaling pathway was shown to be involved in hepatic insulin sensitivity. However, compared to vascular tissues, there is only limited knowledge about the underlying signaling pathways in the liver. Therefore, we employed an LC-MS/MS-based time-resolved phosphoproteomics approach to characterize 11,12-EET-mediated signaling events in the liver cell line Hepa 1-6. 11,12-EET treatment resulted in the time-dependent regulation of phosphopeptides involved in processes as yet unknown to be affected by EETs, including RNA processing, splicing and translation regulation. Pathway analysis combined with western blot-based validation revealed enhanced AKT/mTOR/p70S6K signaling as demonstrated by increased acute phosphorylation of AKT (Ser473) and p70S6K (Thr389). In addition, 11,12-EET treatment led to differential regulation of phosphopeptides including important mediators of the DNA damage response and we observed a prolonged induction of the etoposide-induced DNA damage marker ??H2AX in response to 11,12-EET. In summary, our findings extend current knowledge of 11,12-EET signaling events and emphasize the importance of the AKT/mTOR/p70S6K pathway in hepatic 11,12-EET signaling. Based on the results presented in this study, we furthermore propose a novel role of EET signaling in the regulation of the DNA damage response.
HostingRepository	PRIDE
AnnounceDate	2019-11-27
AnnouncementXML	Submission_2019-11-27_06:52:36.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marco Rahm
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2019-08-30 04:09:31	ID requested
1	2019-11-06 02:06:55	announced
⏵ 2	2019-11-27 06:52:37	announced	2019-11-27: Updated project metadata.

Rahm M, Merl-Pham J, Adamski J, Hauck SM, Time-resolved phosphoproteomic analysis elucidates hepatic 11,12-Epoxyeicosatrienoic acid signaling pathways. Prostaglandins Other Lipid Mediat, 146():106387(2020) [pubmed]

curator keyword: Biological

submitter keyword: Lipid Signaling, AKT/mTOR/p70S6K pathway, Eicosanoids, LC-MS/MS, TiO2

Stefanie M. Hauck
contact affiliation	Research Unit Protein Science, Helmholtz Zentrum M??nchen, German Research Center for Environmental Health GmbH, Ingolst??dter Landstra??e 1, D-85764 Neuherberg, Germany
contact email	hauck@helmholtz-muenchen.de
lab head
Marco Rahm
contact affiliation	Helmholtz Zentrum M??nchen
contact email	rahm.helmholtz@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD015245
     1. Label: PRIDE project
     2. Name: Time-resolved Phosphoproteomic Analysis Elucidates Hepatic 11,12-Epoxyeicosatrienoic Acid Signaling Pathways