RNA-dependent protein kinase PKR is required for activation of NF-κB by IFN-γ in a STAT1-independent pathway
RNA-dependent protein kinase PKR is required for activation of NF-κB by IFN-γ in a STAT1-independent pathway
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DOI：
10.4049/jimmunol.166.10.6170
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发表时间：
2001-05-15
影响因子：
4.4
通讯作者：
Williams, BRG
中科院分区：
文献类型：
--
作者：
Deb, A;Haque, SJ;Williams, BRG
ifn诱导的dsrna激活蛋白激酶PKR通过磷酸化真核起始因子-2 α来调节蛋白质合成。它还作为转录因子NF-kappaB、IFN调节因子-1和激活转录因子-2的信号换能器。ifn - γ是一种多效细胞因子，通过激活Janus激酶- stat信号通路引发基因表达。ifn - γ可以与tnf - α协同激活许多细胞系中的NF-kappaB。本研究表明，ifn - γ可以通过Janus激酶-1介导但不依赖于stat1的机制激活NF-kappaB。ifn - γ激活NF-kappaB与IKB β的降解kappa有关。ifn - γ反应可以通过2',5'-寡核苷酸连接的反义嵌合体阻断PKR mRNA。在pkn缺失的细胞中，IFN没有激活NF-kappaB，这表明IFN- γ信号传导到NF-kappaB需要PKR。
The IFN-inducible dsRNA-activated protein kinase PKR regulates protein synthesis through phosphorylation of eukaryotic initiation factor-2 alpha. It also acts as a signal transducer for transcription factors NF-kappaB, IFN regulatory factor-1, and activating transcription factor-2. IFN-gamma, a pleiotropic cytokine, elicits gene expression by activating the Janus kinase-STAT signaling pathway. IFN-gamma can synergize with TNF-alpha to activate NF-kappaB in a number of cell lines. Here we show that IFN-gamma alone can activate NF-kappaB, by a Janus kinase-1-mediated, but Stat1-independent, mechanism. NF-kappaB activation by IFN-gamma is associated with degradation kappa of IKB beta. The IFN-gamma response can be blocked by 2',5'-oligoadenylate-linked antisense chimeras against PKR mRNA. There was no activation of NF-kappaB by IFN in PKR-null cells, indicating that PKR is required for IFN-gamma signaling to NF-kappaB.