TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta.
Nat Immunol
; 9(4): 361-8, 2008 Apr.
Article
em En
| MEDLINE
| ID: mdl-18297073
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Membrana Transportadoras
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Glicoproteínas de Membrana
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Transdução de Sinais
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Interferon beta
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Endocitose
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Receptor 4 Toll-Like
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article