Involvement of TIRAP/MAL in signaling for the activation of interferon regulatory factor 3 by lipopolysaccharide

FEBS Letters

Fukuhara, Yukiko¹  Yoneyama, Mitsutoshi¹  Fujita, Takashi¹  Iwamura, Tomokatsu¹  Suhara, Wakako¹  Yamaguchi, Kazumi¹  Amano, Fumio²  Shinobu, Noriaki¹ 

[1] Department of Tumor Cell Biology, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan;Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan

关键词: Lipopolysaccharide;    Toll-like receptor;    Interferon;    Interferon regulatory factor;    TIR domain-containing adapter protein;    MyD88 adapter like;    IFN;    interferon;    IRF;    IFN regulatory factor;    ISRE;    IFN-stimulated response element;    EMSA;    electrophoretic mobility shift assay;    TIR;    Toll-interleukin 1 receptor;    TIRAP/MAL;    TIR domain-containing adapter protein/MyD88 adapter like;    dsRNA;    double-stranded RNA;    LPS;    lipopolysaccharide;    TLR;    Toll-like receptor;    IKK;    IκB kinase;    CBP;    CREB binding protein;    TPCK;    N-tosyl-L-phenylalanine chloromethyl ketone;    TLCK;    Nα-p-tosyl-L-lysine chloromethyl ketone;    PAGE;    polyacrylamide gel electrophoresis;   

DOI  :  10.1016/S0014-5793(02)02636-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Infections of bacteria and viruses induce host defense reactions known as innate responses that include the production of cytokines and chemokines. The production of type I interferon (IFN) is known to be induced by viral double-stranded (ds) RNA or bacterial lipopolysaccharide (LPS). Although important functions for the transcription factors NF-κB and interferon regulatory factor-3 (IRF-3) are indicated, the molecular signals leading to the activation of IFN genes have yet to be elucidated. We provide several lines of evidence that LPS and dsRNA trigger distinct intracellular signals upstream. Notably, our investigation revealed a critical function for TIRAP/MAL, a signaling adapter for Toll-like receptor (TLR) 4, in LPS-induced but not dsRNA-induced activation of IRF-3. These results highlight cross-talk between TLR-mediated and virus/dsRNA-induced signals resulting in activation of the IFN system.

【 授权许可】

Unknown