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PXD071978-1

PXD071978 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleRAS P21 Protein Activator 3 constrains Type I Immunity by limiting HCK kinase-mediated STAT4 phosphorylation
DescriptionType I immunity, mediated by IFN-γ, is essential for combating intracellular pathogens but also drives inflammatory diseases. While the IL-12-STAT4 pathway that promotes IFN-γ production is well-established, the intrinsic negative regulators remain poorly defined. We identify RASA3 as a critical negative regulator whose expression is downregulated during Th1 cell differentiation. Its T cell-specific ablation amplified Th1/Tc1 responses, enhancing clearance of Listeria monocytogenes but exacerbating allergic contact dermatitis. Mechanistically, RASA3 constrains IFN-γ production by repressing the translation of the hematopoietic cell kinase (HCK) via ribosomal protein RPL36A. We further identify HCK as a novel direct kinase for STAT4, which binds to and phosphorylates it at Tyr693 residue. Additionally, the RASA3-HCK axis is conserved in human Th1 cells. Our work establishes RASA3 as a fundamental brake on type I immunity and a previously unrecognized role for HCK in STAT4 phosphorylation, presenting new potential targets for modulating Th1/Tc1-driven immune responses.
HostingRepositoryiProX
AnnounceDate2025-12-12
AnnouncementXMLSubmission_2026-07-06_02:02:49.138.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJiayu Song
SpeciesList scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-12-14 18:58:22ID requested
12026-07-06 02:02:49announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: RASA3, HCK, STAT4, RPL36A
Contact List
Bing Wu
contact affiliationWuhan University
contact emailbingwu@whu.edu.cn
lab head
Jiayu Song
contact affiliationWuhan University
contact email18326151404@139.com
dataset submitter
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