Deficient cytokine signaling in mouse embryo fibroblasts with a targeted deletion in the PKR gene: Role of IRF-1 and NF-kappa B
Deficient cytokine signaling in mouse embryo fibroblasts with a targeted deletion in the PKR gene: Role of IRF-1 and NF-kappa B
复制标题
DOI：
10.1093/emboj/16.2.406
复制
发表时间：
1997-01-15
期刊：
影响因子：
11.4
通讯作者：
Williams, BRG
中科院分区：
文献类型：
--
作者：
Kumar, A;Yang, YL;Williams, BRG
干扰素诱导的双链RNA(DsRNA)激活的丝氨酸/苏氨酸蛋白激酶(PKR)在干扰素的抗病毒和抗增殖效应中发挥作用，PKR磷酸化起始因子eIF2α，从而抑制蛋白质合成，还通过磷酸化核因子-kappa B的抑制物ikappa B而激活转录因子核因子-kappa B(NF-kappa B)。在来自PKR(o/o)小鼠的胚胎成纤维细胞中，干扰素调节因子1(IRF-1)或鸟苷酸结合蛋白(GBP)启动子-报告构建体对干扰素-γ或PIC无反应，但可通过与PKR共转染恢复反应，缺乏反应性可归因于IRF-1和/或核因子-kappaB对干扰素-γ或DIC的反应减弱。因此，PKR作为依赖于转录因子IRF-1和NF-kappa B的干扰素刺激基因的信号转导。
The interferon (IFN)-indueed double-stranded RNA (dsRNA)-activated Ser/Thr protein kinase (PKR) plays a role in the antiviral and antiproliferative effects of IFN, PKR phosphorylates initiation factor eIF2 alpha, thereby inhibiting protein synthesis, and also activates the transcription factor, nuclear factor-kappa B (NF-kappa B), by phosphorylating the inhibitor of NF-kappa B, I kappa B. Mice devoid of functional PKR (Pkr(o/o)) derived by targeted gene disruption exhibit a diminished response to IFN-gamma and poly(rI:rC) (pIC). In embryo fibroblasts derived from Pkr(o/o) mice, interferon regulatory factor 1 (IRF-1) or guanylate binding protein (Gbp) promoter-reporter constructs were unresponsive to IFN-gamma or pIC but response could be restored by co-transfection with PKR, The lack of responsiveness could be attributed to a diminished activation of IRF-1 and/or NF-kappa B in response to IFN-gamma or DIC. Thus, PKR acts as a signal transducer for IFN-stimulated genes dependent on the transcription Factors IRF-1 and NF-kappa B.