Trif-related adapter molecule is phosphorylated by PKC{epsilon} during Toll-like receptor 4 signaling.
Proc Natl Acad Sci U S A
; 103(24): 9196-201, 2006 Jun 13.
Article
em En
| MEDLINE
| ID: mdl-16757566
ABSTRACT
PKCepsilon has been shown to play a key role in the effect of the Gram-negative bacterial product LPS; however, the target for PKCepsilon in LPS signaling is unknown. LPS signaling is mediated by Toll-like receptor 4, which uses four adapter proteins, MyD88, MyD88 adapter-like (Mal), Toll/IL-1R domain-containing adapter inducing IFN-beta (Trif), and Trif-related adapter molecule (TRAM). Here we show that TRAM is transiently phosphorylated by PKCepsilon on serine-16 in an LPS-dependent manner. Activation of IFN regulatory factor 3 and induction of the chemokine RANTES, which are both TRAM-dependent, were attenuated in PKCepsilon-deficient cells. TRAMS16A is inactive when overexpressed and is attenuated in its ability to reconstitute signaling in TRAM-deficient cells. We have therefore uncovered a key process in Toll-like receptor 4 signaling, identifying TRAM as the target for PKCepsilon.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Receptores de Interleucina
/
Proteínas Adaptadoras de Transdução de Sinal
/
Proteína Quinase C-épsilon
/
Receptor 4 Toll-Like
/
Isoenzimas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2006
Tipo de documento:
Article