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PXD014621

DataSet Summary

  • HostingRepository: PanoramaPublic
  • AnnounceDate: 2019-07-15
  • AnnouncementXML: Submission_2019-07-15_11:37:10.xml
  • DigitalObjectIdentifier:
  • ReviewLevel: Peer-reviewed dataset
  • DatasetOrigin: Original data
  • RepositorySupport: Supported dataset by repository
  • PrimarySubmitter: Tanya Freedman
  • Title: Unique-region phosphorylation targets LynA for rapid degradation, tuning its expression and signaling in myeloid cells
  • Description: The 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.
  • SpeciesList: scientific name: Mus musculus; NCBI TaxID: 10090;
  • ModificationList: Phospho; Label:13C(5)15N(1)
  • Instrument: Orbitrap Fusion

Dataset History

VersionDatetimeStatusChangeLog Entry
02019-07-15 11:32:17ID requested
12019-07-15 11:37:11announced

Publication List

  1. 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

  1. submitter keyword: SFK LYN A, Degadation, macrophage, Kinase, phosphoprotein

Contact List

    Tanya Freedman
    • contact affiliation: University of MInnesota- Twin Cities
    • contact email: tfreedma@umn.edu
    • lab head:
    Tanya Freedman
    • contact affiliation: University of MInnesota- Twin Cities
    • contact email: tfreedma@umn.edu
    • dataset submitter:

Full Dataset Link List

  1. Panorama Public dataset URI

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