PXD025319 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Redox regulation of PTPN22 affects the severity of T cell dependent autoimmune inflammation |
Description | PTPN22, a modifier of T cell receptor signaling, and reactive oxygen species are major players in the regulation of chronic autoimmune diseases. As with all protein tyrosine phosphatases the activity of PTPN22 is redox regulated, but if or how such regulation can modulate inflammatory pathways in vivo is not known. To determine this, we created a mouse with a cysteine-to-serine mutation at position 129 in PTPN22 (C129S), a residue proposed to alter the redox regulatory properties of PTPN22 by forming a disulfide with the catalytic C227 residue. The C129S mutant mouse showed a stronger T cell-dependent inflammatory response due to enhanced TCR signaling and activation of T cells. Activity assays with purified proteins suggest that the functional results can be explained by an increased sensitivity to oxidation of the C129S mutated PTPN22 protein. We also observed that the disulfide of native PTPN22 can be directly reduced by the thioredoxin system, while the C129S mutant lacking this disulfide was less amenable to reductive reactivation. In conclusion, we show in the mouse that the non-catalytic C129 residue of PTPN22 modulates its redox regulatory properties, and that oxidation-prone PTPN22 leads to increased severity in the development of T cell-dependent autoimmunity. |
HostingRepository | PRIDE |
AnnounceDate | 2022-03-23 |
AnnouncementXML | Submission_2022-03-23_07:40:10.573.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Amir Ata Saei |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-04-12 07:59:25 | ID requested | |
⏵ 1 | 2022-03-23 07:40:10 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Autoimmunity, PTPN22, reactive oxygen species, lymphocyte signaling |
Contact List
Prof. Roman. A. Zubarev |
contact affiliation | Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden |
contact email | Roman.zubarev@ki.se |
lab head | |
Amir Ata Saei |
contact affiliation | Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden |
contact email | amirata.saei.dibavar@ki.se |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD025319
- Label: PRIDE project
- Name: Redox regulation of PTPN22 affects the severity of T cell dependent autoimmune inflammation