| First Author | Kagan JC | Year | 2008 |
| Journal | Nat Immunol | Volume | 9 |
| Issue | 4 | Pages | 361-8 |
| PubMed ID | 18297073 | Mgi Jnum | J:133314 |
| Mgi Id | MGI:3778252 | Doi | 10.1038/ni1569 |
| Citation | Kagan JC, et al. (2008) TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta. Nat Immunol 9(4):361-8 |
| abstractText | Toll-like receptor 4 (TLR4) induces two distinct signaling pathways controlled by the TIRAP-MyD88 and TRAM-TRIF pairs of adaptor proteins, which elicit the production of proinflammatory cytokines and type I interferons, respectively. How TLR4 coordinates the activation of these two pathways is unknown. Here we show that TLR4 activated these two signaling pathways sequentially in a process organized around endocytosis of the TLR4 complex. We propose that TLR4 first induces TIRAP-MyD88 signaling at the plasma membrane and is then endocytosed and activates TRAM-TRIF signaling from early endosomes. Our data emphasize a unifying theme in innate immune recognition whereby all type I interferon-inducing receptors signal from an intracellular location. |
