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dc.contributor.authorBrian, Ben F
dc.contributor.authorJolicoeur, Adrienne S
dc.contributor.authorGuerrero, Candace R.
dc.contributor.authorNunez, Myra G
dc.contributor.authorSychev, Zoi E
dc.contributor.authorHegre, Siv Anita
dc.contributor.authorSætrom, Pål
dc.contributor.authorHabib, Nagy
dc.contributor.authorDrake, Justin M
dc.contributor.authorSchwertfeger, Kathryn L
dc.contributor.authorFreedman, Tanya S.
dc.date.accessioned2020-02-19T08:12:14Z
dc.date.available2020-02-19T08:12:14Z
dc.date.created2019-10-25T14:45:30Z
dc.date.issued2019
dc.identifier.issn2050-084X
dc.identifier.urihttp://hdl.handle.net/11250/2642445
dc.description.abstractThe activity of Src-family kinases (SFKs), which phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs), is a critical factor regulating myeloid-cell activation. We reported previously that the SFK LynA is uniquely susceptible to rapid ubiquitin-mediated degradation in macrophages, functioning as a rheostat regulating signaling (Freedman et al., 2015). 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 derived from mice. 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 thus builds cell specificity into the LynA checkpoint.nb_NO
dc.language.isoengnb_NO
dc.publishereLife Sciences Publicationsnb_NO
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleUnique-region phosphorylation targets LynA for rapid degradation, tuning its expression and signaling in myeloid cellsnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionpublishedVersionnb_NO
dc.source.volume8nb_NO
dc.source.journaleLIFEnb_NO
dc.identifier.doi10.7554/eLife.46043
dc.identifier.cristin1740672
dc.relation.projectNorges forskningsråd: 230338nb_NO
dc.description.localcodeCopyright Brian et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.nb_NO
cristin.unitcode194,65,15,0
cristin.unitcode194,63,10,0
cristin.unitnameInstitutt for klinisk og molekylær medisin
cristin.unitnameInstitutt for datateknologi og informatikk
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2


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