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PXD005659

PXD005659 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleQuantitative liver proteomics identifies FGF19 targets that couple metabolism and proliferation
DescriptionFibroblast growth factor 19 (FGF19) is a gut-derived peptide hormone that is produced following activation of Farnesoid X Receptor (FXR). FGF19 is secreted and signals to the liver, where it contributes to the homeostasis of bile acid (BA), lipid and carbohydrate metabolism. FGF19 is a promising therapeutic target in metabolic syndrome and cholestatic diseases, but enthusiasm for its use has been tempered by FGF19-mediated induction of proliferation and hepatocellular carcinoma. To inform future rational design of FGF19-variants, we have conducted temporal quantitative proteomic and gene expression analyses to identify FGF19-targets related to metabolism and proliferation. Mice were fasted for 16 hours, and injected with human FGF19 (1 mg/kg body weight) or vehicle. Liver protein extracts (containing 'light' lysine) were mixed 1:1 with a spike-in protein extract from 13C6-lysine metabolically labelled mouse liver (containing 'heavy' lysine) and analysed by LC-MS/MS. Our analyses provide a resource of FGF19 target proteins in the liver. 189 proteins were upregulated (≥ 1.5 folds) and 73 proteins were downregulated (≤ -1.5 folds) by FGF19. FGF19 treatment decreased the expression of proteins involved in fatty acid (FA) synthesis, i.e. Fabp5, Scd1, and Acsl3 and increased the expression of Acox1, involved in FA oxidation. As expected, FGF19 increased the expression of proteins known to drive proliferation (i.e. Tgfbi, Vcam1, Anxa2 and Hdlbp). Importantly, many of the FGF19 targets (i.e. Pdk4, Apoa4, Fas and Stat3) have a dual function in both metabolism and cell proliferation. Therefore, our findings challenge the development of FGF19-variants that uncouple full metabolic benefit from mitogenic potential.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:34:36.112.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHarmjan Vos
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListdeaminated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion ETD
Dataset History
RevisionDatetimeStatusChangeLog Entry
02017-01-05 01:44:26ID requested
12017-02-15 11:20:34announced
22024-10-22 04:34:43announced2024-10-22: Updated project metadata.
Publication List
Massafra V, Milona A, Vos HR, Burgering BM, van Mil SW, Quantitative liver proteomics identifies FGF19 targets that couple metabolism and proliferation. PLoS One, 12(2):e0171185(2017) [pubmed]
10.1371/journal.pone.0171185;
Keyword List
curator keyword: Biological, Biomedical
submitter keyword: FGF19
growth factor
FXR
liver
proteomics
metabolism
proliferation
TGF
Contact List
Saskia W.C. van Mil
contact affiliationCenter for Molecular Medicine, UMC Utrecht, Utrecht, The Netherlands
contact emailS.W.C.vanMil@umcutrecht.nl
lab head
Harmjan Vos
contact affiliationUniversity Medical Center Utrecht Dept. Molecular Cancer Research
contact emailh.r.vos-3@umcutrecht.nl
dataset submitter
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Dataset FTP location
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PRIDE project URI
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