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Phosphorylation of iRhom2 Controls Stimulated Proteolytic Shedding by the Metalloprotease ADAM17/TACE

2017Journal article Open access
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dc.contributor.authorCavadas, Miguel
dc.contributor.authorOikonomidi, Ioanna
dc.contributor.authorGaspar, Catarina J.
dc.contributor.authorBurbridge, Emma
dc.contributor.authorBadenes, Marina
dc.contributor.authorFélix, Inês
dc.contributor.authorBolado, Alfonso
dc.contributor.authorHu, Tianyi
dc.contributor.authorBileck, Andrea
dc.contributor.authorGerner, Christopher
dc.contributor.authorDomingos, Pedro M.
dc.contributor.authorvon Kriegsheim, Alex
dc.contributor.authorAdrain, Colin
dc.date.accessioned2019-12-09T23:16:57Z
dc.date.available2019-12-09T23:16:57Z
dc.date.issued2017
dc.description.abstractCell surface metalloproteases coordinate signaling during development, tissue homeostasis, and disease. TACE (TNF-α-converting enzyme), is responsible for cleavage ("shedding") of membrane-tethered signaling molecules, including the cytokine TNF, and activating ligands of the EGFR. The trafficking of TACE within the secretory pathway requires its binding to iRhom2, which mediates the exit of TACE from the endoplasmic reticulum. An important, but mechanistically unclear, feature of TACE biology is its ability to be stimulated rapidly on the cell surface by numerous inflammatory and growth-promoting agents. Here, we report a role for iRhom2 in TACE stimulation on the cell surface. TACE shedding stimuli trigger MAP kinase-dependent phosphorylation of iRhom2 N-terminal cytoplasmic tail. This recruits 14-3-3 proteins, enforcing the dissociation of TACE from complexes with iRhom2, promoting the cleavage of TACE substrates. Our data reveal that iRhom2 controls multiple aspects of TACE biology, including stimulated shedding on the cell surface.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.celrep.2017.09.074pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/911
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationWorldwide Cancer Research (14-1289)pt_PT
dc.relationMarie Curie Career Integration Grant (project no. 618769)pt_PT
dc.relationFCT grants SFRH/BCC/52507/2014pt_PT
dc.relationFCT grants PTDC/BEX-BCM/3015/ 2014pt_PT
dc.relationCOST (BM1406)pt_PT
dc.relationFCT grants LISBOA-01-0145-FEDER- 007660, FCT-ANR/NEU-NMC/0006/2013, PTDC/NEU-NMC/2459/2014, and IF/00697/2014.pt_PT
dc.relationFCT grant SFRH/ BPD/117216/2016pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subject14-3-3 Proteinspt_PT
dc.subjectADAM17 Proteinpt_PT
dc.subjectAnimalspt_PT
dc.subjectCarrier Proteinspt_PT
dc.subjectCell Membranept_PT
dc.subjectEndoplasmic Reticulumpt_PT
dc.subjectHEK293 Cellspt_PT
dc.subjectHumanspt_PT
dc.subjectMice, Knockoutpt_PT
dc.subjectMitogen-Activated Protein Kinasespt_PT
dc.subjectPhosphorylationpt_PT
dc.subjectPhosphoserinept_PT
dc.subjectSignal Transductionpt_PT
dc.subjectSubstrate Specificitypt_PT
dc.subjectToll-Like Receptorspt_PT
dc.subjectProteolysispt_PT
dc.titlePhosphorylation of iRhom2 Controls Stimulated Proteolytic Shedding by the Metalloprotease ADAM17/TACEpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage757pt_PT
oaire.citation.issue3pt_PT
oaire.citation.startPage745pt_PT
oaire.citation.titleCell Reportspt_PT
oaire.citation.volume21pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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