DOUBLE-STRANDED RNA-DEPENDENT PROTEIN-KINASE ACTIVATES TRANSCRIPTION FACTOR NF-KAPPA-B BY PHOSPHORYLATING I-KAPPA-B

被引:520
作者
KUMAR, A
HAQUE, J
LACOSTE, J
HISCOTT, J
WILLIAMS, BRG
机构
[1] CLEVELAND CLIN FDN,DEPT CANC BIOL,CLEVELAND,OH 44195
[2] SIR MORTIMER B DAVIS JEWISH HOSP,LADY DAVIS INST MED RES,MONTREAL H3T 1E2,PQ,CANADA
[3] UNIV TORONTO,DEPT MOLEC & MED GENET,TORONTO M5S 1A8,ON,CANADA
关键词
D O I
10.1073/pnas.91.14.6288
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:6288 / 6292
页数:5
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