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dc.contributor.authorBOWIE, ANDREWen
dc.date.accessioned2015-12-14T12:57:59Z
dc.date.available2015-12-14T12:57:59Z
dc.date.issued2014en
dc.date.submitted2014en
dc.identifier.citationVerstak B, Stack J, Ve T, Mangan M, Hjerrild K, Jeon J, Stahl R, Latz E, Gay N, Kobe B, Bowie AG, Mansell A, The TLR signaling adaptor TRAM interacts with TRAF6 to mediate activation of the inflammatory response by TLR4., Journal of leukocyte biology, 96, 3, 2014, 427-36en
dc.identifier.issn0741-5400en
dc.identifier.otherYen
dc.descriptionPUBLISHEDen
dc.description.abstractTLRs act as sentinels in professional immune cells to detect and initiate the innate immune response to pathogen challenge. TLR4 is a widely expressed TLR, responsible for initiating potent immune responses to LPS. TRAM acts to bridge TLR4 with TRIF, orchestrating the inflammatory response to pathogen challenge. We have identified a putative TRAF6-binding motif in TRAM that could mediate a novel signaling function for TRAM in TLR4 signaling. TRAM and TRAF6 association was confirmed by immunoprecipitation of endogenous, ectopically expressed and recombinant proteins, which was ablated upon mutation of a key Glu residue in TRAM (TRAM E183A). TRAF6 and TRAM were observed colocalizing using confocal microscopy following ectopic expression in cells and the ability of TRAM and TRAM E183A to activate luciferase-linked reporter assays was determined in HEK293 and TRAF6-deficient cells. Importantly, TRAM-deficient macrophages reconstituted with TRAM E183A display significantly reduced inflammatory TNF-α, IL-6, and RANTES protein production compared with WT TRAM. These results demonstrate a novel role for TRAM in TLR4-mediated signaling in regulating inflammatory responses via its interaction with TRAF6, distinct from its role as a bridging adaptor between TLR4 and TRIF.en
dc.format.extent427-36en
dc.relation.ispartofseriesJournal of leukocyte biologyen
dc.relation.ispartofseries96en
dc.relation.ispartofseries3en
dc.rightsYen
dc.subjectToll-like receptorsen
dc.subjectinnate immunityen
dc.subjectinflammationen
dc.subjectsignal transductionen
dc.titleThe TLR signaling adaptor TRAM interacts with TRAF6 to mediate activation of the inflammatory response by TLR4.en
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/agbowieen
dc.identifier.rssinternalid107606en
dc.identifier.doihttp://dx.doi.org/10.1189/jlb.2A0913-487Ren
dc.rights.ecaccessrightsopenAccess
dc.identifier.urihttp://hdl.handle.net/2262/75318


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