PXD056827 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Regulation of Leucine-Rich Repeat Kinase 2 by inflammation and IL-4 |
Description | Mutations in Leucine-Rich Repeat protein Kinase 2 (LRRK2) are associated with Parkinson's Disease (PD) and Crohn's Disease (CD), but the regulation of LRRK2 during inflammation remains relatively unexplored. Here we developed a flow cytometry-based assay to assess LRRK2 activity in individual cells and created an EGFP-Lrrk2-knock-in reporter mouse to analyse cell-specific LRRK2 expression. Using these tools, we catalogued LRRK2 levels and activity in splenic and intestinal immune cells. Inflammation increased LRRK2 expression and activity in B-cells, immature neutrophils and immature monocytes, but decreased these in dendritic cells and eosinophils. In mature neutrophils, inflammation stimulated activity but reduced LRRK2 expression. A kinase-activating PD-associated LRRK2-R1441C mutation exacerbated inflammation-induced activation of LRRK2 specifically in monocytes and macrophages without affecting LRRK2 levels. Finally, we identified IL-4 as a novel factor that upregulated LRRK2 expression and activity in B-cells,replicating inflammatory effects observed in vivo. Our findings provide valuable new insights into the regulation of the LRRK2 pathway in immune cells, crucial for understanding LRRK2 and its therapeutic potential in inflammatory diseases such as CD. |
HostingRepository | PRIDE |
AnnounceDate | 2025-03-04 |
AnnouncementXML | Submission_2025-03-04_14:28:21.870.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Andrew Howden |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-10-15 14:38:44 | ID requested | |
⏵ 1 | 2025-03-04 14:28:22 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: inflammation,LRRK2, IL4 |
Contact List
Dr Mahima Swamy |
contact affiliation | MRC PPU School of Life Sciences University of Dundee Dundee UK, DD1 5EH |
contact email | m.swamy@dundee.ac.uk |
lab head | |
Andrew Howden |
contact affiliation | University of Dundee |
contact email | a.howden@dundee.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD056827
- Label: PRIDE project
- Name: Regulation of Leucine-Rich Repeat Kinase 2 by inflammation and IL-4