| http://purl.uniprot.org/citations/25385819 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25385819 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25385819 | http://www.w3.org/2000/01/rdf-schema#comment | "Detection of microbes by TLRs on the plasma membrane leads to the induction of proinflammatory cytokines such as TNF-α, via activation of NF-κB. Alternatively, activation of endosomal TLRs leads to the induction of type I IFNs via IFN regulatory factors (IRFs). TLR4 signaling from the plasma membrane to NF-κB via the Toll/IL-1R (TIR) adaptor protein MyD88 requires the TIR sorting adaptor Mal, whereas endosomal TLR4 signaling to IRF3 via the TIR domain-containing adaptor-inducing IFN-β (TRIF) requires the TRIF-related adaptor molecule (TRAM). Similar to TLR4 homodimers, TLR2 heterodimers can also induce both proinflammatory cytokines and type I IFNs. TLR2 plasma membrane signaling to NF-κB is known to require MyD88 and Mal, whereas endosomal IRF activation by TLR2 requires MyD88. However, it was unclear whether TLR2 requires a sorting adaptor for endosomal signaling, like TLR4 does. In this study, we show that TLR2-dependent IRF7 activation at the endosome is both Mal- and TRAM-dependent, and that TRAM is required for the TLR2-dependent movement of MyD88 to endosomes following ligand engagement. TRAM interacted with both TLR2 and MyD88, suggesting that TRAM can act as a bridging adapter between these two molecules. Furthermore, infection of macrophages lacking TRAM with herpes viruses or the bacterium Staphylococcus aureus led to impaired induction of type I IFN, indicating a role for TRAM in TLR2-dependent responses to human pathogens. Our work reveals that TRAM acts as a sorting adaptor not only for TLR4, but also for TLR2, to facilitate signaling to IRF7 at the endosome, which explains how TLR2 is capable of causing type I IFN induction."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.1401605"xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.1401605"xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/author | "Bowie A.G."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/author | "Bowie A.G."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/author | "Paludan S.R."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/author | "Paludan S.R."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/author | "Reinert L.S."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/author | "Reinert L.S."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/author | "Doyle S.L."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/author | "Doyle S.L."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/author | "McLoughlin R.M."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/author | "McLoughlin R.M."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/author | "Connolly D.J."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/author | "Connolly D.J."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/author | "Stack J."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/author | "Stack J."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/author | "O'Keeffe K.M."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/author | "O'Keeffe K.M."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/name | "J. Immunol."xsd:string |
| http://purl.uniprot.org/citations/25385819 | http://purl.uniprot.org/core/name | "J. Immunol."xsd:string |