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LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF.
Fitzgerald, Katherine A; Rowe, Daniel C; Barnes, Betsy J; Caffrey, Daniel R; Visintin, Alberto; Latz, Eicke; Monks, Brian; Pitha, Paula M; Golenbock, Douglas T.
Afiliação
  • Fitzgerald KA; Division of Infectious Disease and Immunology, Department of Medicine, The University of Massachusetts Medical School, Worcester, MA 01605, USA.
J Exp Med ; 198(7): 1043-55, 2003 Oct 06.
Article em En | MEDLINE | ID: mdl-14517278
ABSTRACT
Toll-IL-1-resistance (TIR) domain-containing adaptor-inducing IFN-beta (TRIF)-related adaptor molecule (TRAM) is the fourth TIR domain-containing adaptor protein to be described that participates in Toll receptor signaling. Like TRIF, TRAM activates interferon regulatory factor (IRF)-3, IRF-7, and NF-kappaB-dependent signaling pathways. Toll-like receptor (TLR)3 and 4 activate these pathways to induce IFN-alpha/beta, regulated on activation, normal T cell expressed and secreted (RANTES), and gamma interferon-inducible protein 10 (IP-10) expression independently of the adaptor protein myeloid differentiation factor 88 (MyD88). Dominant negative and siRNA studies performed here demonstrate that TRIF functions downstream of both the TLR3 (dsRNA) and TLR4 (LPS) signaling pathways, whereas the function of TRAM is restricted to the TLR4 pathway. TRAM interacts with TRIF, MyD88 adaptor-like protein (Mal)/TIRAP, and TLR4 but not with TLR3. These studies suggest that TRIF and TRAM both function in LPS-TLR4 signaling to regulate the MyD88-independent pathway during the innate immune response to LPS.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Glicoproteínas de Membrana / Transdução de Sinais / Lipopolissacarídeos / NF-kappa B / Receptores de Superfície Celular / Proteínas Adaptadoras de Transporte Vesicular / Proteínas de Ligação a DNA Limite: Animals / Humans Idioma: En Revista: J Exp Med Ano de publicação: 2003 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Glicoproteínas de Membrana / Transdução de Sinais / Lipopolissacarídeos / NF-kappa B / Receptores de Superfície Celular / Proteínas Adaptadoras de Transporte Vesicular / Proteínas de Ligação a DNA Limite: Animals / Humans Idioma: En Revista: J Exp Med Ano de publicação: 2003 Tipo de documento: Article País de afiliação: Estados Unidos