DOUBLE-STRANDED RNA-DEPENDENT PROTEIN-KINASE ACTIVATES TRANSCRIPTION FACTOR NF-KAPPA-B BY PHOSPHORYLATING I-KAPPA-B
DOUBLE-STRANDED RNA-DEPENDENT PROTEIN-KINASE ACTIVATES TRANSCRIPTION FACTOR NF-KAPPA-B BY PHOSPHORYLATING I-KAPPA-B
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DOI：
10.1073/pnas.91.14.6288
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发表时间：
1994-07-05
影响因子：
11.1
通讯作者：
WILLIAMS, BRG
中科院分区：
文献类型：
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作者：
KUMAR, A;HAQUE, J;WILLIAMS, BRG
病毒或双链RNA （dsRNA）诱导干扰素（IFN）基因需要在IFN基因启动子的应答性DNA元件上组装一组复杂的转录因子。调控ifn - β基因转录的必要因子之一是核因子NF-kappa B，其激活由dsRNA触发。先前有研究表明，dsRNA激活的p68蛋白激酶（PKR）可能作为一种诱导受体，通过磷酸化I κ B抑制剂将信号从dsRNA转导到NF-kappa B。我们在体外提供了直接证据，PKR可以磷酸化I κ B α (MAD-3)并激活NF-kappa B DNA结合活性。我们进一步表明，dsRNA诱导了一种不寻常的I κ b - α磷酸化形式。在体内，一个跨显性突变体PKR的表达能够扰乱dsrna介导的信号通路，表明该激酶在ifn - β基因诱导中起作用。
The induction of interferon (IFN) genes by viruses or double-stranded RNA (dsRNA) requires the assembly of a complex set of transcription factors on responsive DNA elements of IFN gene promoters. One of the factors necessary for regulating IFN-beta gene transcription is nuclear factor NF-kappa B, the activation of which is triggered by dsRNA. It has previously been suggested that the dsRNA-activated p68 protein kinase (PKR) may act as an inducer-receptor, transducing the signal from dsRNA to NF-kappa B through phosphorylation of the inhibitor I kappa B. We present direct evidence that PKR can phosphorylate I kappa B-alpha (MAD-3) and activate NF-kappa B DNA binding activity in vitro. We further show that dsRNA induces an unusual phosphorylated form of I kappa B-alpha. The expression of a transdominant mutant PKR is able to perturb the dsRNA-mediated signaling pathway in vivo, suggesting a role for this kinase in IFN-beta gene induction.