PXD014621

PXD014621 is an original dataset announced via ProteomeXchange.

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.
HostingRepository	PanoramaPublic
AnnounceDate	2019-07-15
AnnouncementXML	Submission_2019-07-15_11:37:10.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Tanya Freedman
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	Phospho; Label:13C(5)15N(1)
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-15 11:32:17	ID requested
⏵ 1	2019-07-15 11:37:11	announced

Brian BF, Jolicoeur AS, Guerrero CR, Nunez MG, Sychev ZE, Hegre SA, S, æ, trom 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]

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

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

Panorama Public dataset URI