| Autor: |
Iwamura, Tomokatsu, Yoneyama, Mitsutoshi, Yamaguchi, Kazumi, Suhara, Wakako, Mori, Wakana, Shiota, Kazutaka, Okabe, Yasutaka, Namiki, Hideo, Fujita, Takashi |
| Předmět: |
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| Zdroj: |
Genes to Cells; Apr2001, Vol. 6 Issue 4, p375, 14p |
| Abstrakt: |
Backgrounds: Infection by virus or treatment with double-stranded RNA (dsRNA) results in the activation of transcription factors including IRF-3, IRF-7 and a pleiotropic regulator NF-κB by specific phosphorylation. These factors are important in triggering a cascade of antiviral responses. A protein kinase that is yet to be identified is responsible for the activation of these factors and plays a key role in the responses. Results: The signal cascade was analysed using sensitive assays for the activation of IRF-3 and NF-κB, and various inhibitors. We found that the activation of IRF-3 and NF-κB by dsRNA or virus involves a process that is sensitive to Geldanamycin. Although the induction of NF-κB by dsRNA/virus and TNF-α involves common downstream pathways including IKK activation, the upstream, Geldanamycin-sensitive process was unique to the dsRNA/virus-induced signal. By an in vitro assay using cell extract, we found an inducible protein kinase activity with physiological specificity of IRF-3 phosphorylation. Furthermore, the same extract specifically phosphorylated IRF-7 in a similar manner. Conclusions: Double-stranded RNA or virus triggers a specific signal cascade that results in the activation of the IRF-3/-7 kinase we detected, which corresponds to the long-sought signalling machinery that is responsible for triggering the early phase of innate response. The signal branches to a common NF-κB activation cascade, thus resulting in the activation of a set of critical transcription factors for the response. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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