| First Author | Meylan E | Year | 2004 |
| Journal | Nat Immunol | Volume | 5 |
| Issue | 5 | Pages | 503-7 |
| PubMed ID | 15064760 | Mgi Jnum | J:89807 |
| Mgi Id | MGI:3041663 | Doi | 10.1038/ni1061 |
| Citation | Meylan E, et al. (2004) RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat Immunol 5(5):503-7 |
| abstractText | Stimulation of Toll-like receptors (TLRs) initiates potent innate immune responses through Toll-interleukin 1 receptor (TIR) domain-containing adaptors such as MyD88 and Trif. Analysis of Trif-deficient mice has shown that TLR3-dependent activation of the transcription factor NF-kappa B by the TLR3 ligand double-stranded RNA is Trif dependent. Here we investigated the 'downstream' signaling events that regulate TLR3-dependent Trif-induced NF-kappa B activation. Trif recruited the kinases receptor interacting protein (RIP)-1 and RIP3 through its RIP homotypic interaction motif. In the absence of RIP1, TLR3-mediated signals activating NF-kappa B, but not the kinase JNK or interferon-beta, were abolished, suggesting that RIP1 mediates Trif-induced NF-kappa B activation. In contrast, the presence of RIP3 negatively regulated the Trif-RIP1-induced NF-kappa B pathway. Therefore, in contrast to other TLRs, which use interleukin 1 receptor-associated kinase (IRAK) proteins to activate NF-kappa B, TLR 3-induced NF-kappa B activation is dependent on RIP kinases. |
