کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2832854 | 1163849 | 2008 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Differential regulation of IKKα-mediated activation of IRF3/7 by NIK Differential regulation of IKKα-mediated activation of IRF3/7 by NIK](/preview/png/2832854.png)
Type I interferons (IFNs) are critical mediators of the innate immune system to defend viral infection. Interferon regulatory factor (IRF) 3 and IRF7 are transcription factors that play critical roles in type I IFN production in response to viral infection. It has been shown that the protein kinase I kappaB kinase alpha (IKKα) is critically involved in IRF7 activation and IFN-α production in Toll-like receptor 7/9 (TLR7/9) signaling cascades. However, overexpression of IKKα does not activate the IFN-α promoters. Here we show that the protein kinase nuclear factor kappaB-inducing kinase (NIK) confers IKKα the ability to activate IRF3/7. Previous studies have shown that NIK phosphorylates IKKα at Ser-176 and Ser-180 residues, and mutation of each of the two residues to glutamate, which mimics its phosphorylation, caused constitutive activation of NF-κB. However, mutation of the two serine residues has differential effects on IKKα-mediated activation of IRF3/7. While IKKα(S176E) constitutively activates IRF3/7, IKKα(S180E) losses its ability to activate IRF3/7. These findings suggest that IKKα-mediated activation of NF-κB and IRF3/7 are differentially regulated by NIK, and NIK plays an important role in TLR7/9-mediated IFN-α production.
Journal: Molecular Immunology - Volume 45, Issue 7, April 2008, Pages 1926–1934