PXD034183 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Phosphorylation of RXRa mediates the effect of JNK to suppress hepatic FGF21 expression and promote metabolic syndrome |
Description | The cJun NH2-terminal kinase (JNK) signaling pathway in the liver promotes systemic changes in metabolism by regulating PPARa-dependent expression of the hepatokine FGF21. Hepatocyte-specific gene ablation studies demonstrated that the Mapk9 gene (encodes JNK2) plays a key mechanistic role. Mutually exclusive inclusion of exons 7a and 7b yields expression of the isoforms JNK2a and JNK2b. Here we demonstrate that Fgf21 gene expression and metabolic regulation is primarily regulated by the JNK2a isoform. To identify relevant substrates of JNK2a, we performed a quantitative phosphoproteomic study of livers isolated from control mice, mice with JNK-deficiency in hepatocytes, and mice that express only JNK2a or JNK2b in hepatocytes. We identified the JNK substrate RXRa as a protein that exhibited JNK2a-promoted phosphorylation in vivo. RXRa functions as a heterodimeric partner of PPARa and may therefore mediate the effects of JNK2a signaling on Fgf21 expression. To test this hypothesis, we established mice with hepatocyte-specific expression of wild-type or mutated RXRa proteins. We found that the RXRa phosphorylation site Ser260 was required for suppression of Fgf21 gene expression. Collectively, these data establish a JNK-mediated signaling pathway that regulates hepatic Fgf21 expression. |
HostingRepository | PRIDE |
AnnounceDate | 2022-10-12 |
AnnouncementXML | Submission_2022-10-12_08:11:00.897.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | MartaIsasa |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | phosphorylated residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-05-29 13:51:28 | ID requested | |
⏵ 1 | 2022-10-12 08:11:01 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: metabolism, FGF21, RXR,JNK, liver, phosphorylation |
Contact List
Roger J.Davis |
contact affiliation | Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. |
contact email | Roger.Davis@umassmed.edu |
lab head | |
MartaIsasa |
contact affiliation | Odyssey Therapeutics |
contact email | isasa.marta@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD034183
- Label: PRIDE project
- Name: Phosphorylation of RXRa mediates the effect of JNK to suppress hepatic FGF21 expression and promote metabolic syndrome