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Physical association between STAT1 and the interferon‐inducible protein kinase PKR and implications for interferon and double‐stranded RNA signaling pathways
Author(s) -
Wong Andrew HoiTao,
Tam Nancy Wai Ning,
Yang YiLi,
Cuddihy Andrew R.,
Li Suiyang,
Kirchhoff Sabine,
Hauser Hansjörg,
Decker Thomas,
Koromilas Antonis E.
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.6.1291
Subject(s) - biology , protein kinase r , interferon , eif 2 kinase , virology , signal transduction , rna , stat1 , protein kinase a , kinase , genetics , mitogen activated protein kinase kinase , gene , cyclin dependent kinase 2
The interferon‐inducible double‐stranded RNA protein kinase PKR controls protein synthesis through the phosphorylation of eukaryotic translation initiation factor (eIF)‐2. In addition to its demonstrated role in translational control, several reports have suggested a transcriptional role for PKR. Here we report that PKR is involved in IFN‐ and dsRNA‐signaling pathways by modulating the function of the signal transducer and activator of transcription STAT1. We also show that PKR associates with STAT1 in mouse and human cells. The association is not a kinase–substrate interaction since STAT1 phosphorylation is not modified by PKR in vitro or in vivo . In addition, the formation of the PKR–STAT1 complex is not dependent upon the enzymatic activity of PKR but does require the dsRNA‐binding domain of PKR. Moreover, there is a concomitant decrease in PKR–STAT1 interaction and increase in STAT1 DNA binding in response to IFNs or dsRNA. These findings suggest that PKR plays an important role in IFN and dsRNA‐signaling pathways by modulating the transcriptional function of STAT1.