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PXD014621

PXD014621 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleUnique-region phosphorylation targets LynA for rapid degradation, tuning its expression and signaling in myeloid cells
DescriptionThe activity of Src-family kinases (SFKs), which phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs), is a critical factor regulating myeloid-cell activation. In a previous paper (Freedman et al., 2015) we showed that the SFK LynA is uniquely susceptible to rapid ubiquitin-mediated degradation in macrophages, functioning as a rheostat regulating signaling. We now report the mechanism by which LynA is preferentially targeted for degradation and how cell specificity is built into the LynA rheostat. Using genetic, biochemical, and quantitative phosphopeptide analyses, we found that the E3 ubiquitin ligase c-Cbl preferentially targets LynA via a phosphorylated tyrosine (Y32) in its unique region. This distinct mode of c-Cbl recognition depresses steady-state expression of LynA in macrophages. Mast cells, however, express little c-Cbl and have correspondingly high LynA. Upon activation, mast-cell LynA is not rapidly degraded, and SFK-mediated signaling is amplified relative to macrophages. Cell-specific c-Cbl expression therefore builds cell specificity into the LynA checkpoint.
HostingRepositoryPanoramaPublic
AnnounceDate2019-07-15
AnnouncementXMLSubmission_2019-07-15_11:37:10.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterTanya Freedman
SpeciesList scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationListPhospho; Label:13C(5)15N(1)
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-07-15 11:32:17ID requested
12019-07-15 11:37:11announced
Publication List
Brian BF, Jolicoeur AS, Guerrero CR, Nunez MG, Sychev ZE, Hegre SA, Sætrom P, Habib N, Drake JM, Schwertfeger KL, Freedman TS, Unique-region phosphorylation targets LynA for rapid degradation, tuning its expression and signaling in myeloid cells. Elife, 8():(2019) [pubmed]
Keyword List
submitter keyword: SFK LYN A, Degadation, macrophage, Kinase, phosphoprotein
Contact List
Tanya Freedman
contact affiliationUniversity of MInnesota- Twin Cities
contact emailtfreedma@umn.edu
lab head
Tanya Freedman
contact affiliationUniversity of MInnesota- Twin Cities
contact emailtfreedma@umn.edu
dataset submitter
Full Dataset Link List
Panorama Public dataset URI