Open AccessDouble-stranded RNA-dependent protein kinase activates transcription factor NF-kappa B by phosphorylating I kappa B.
Author(s) -
Aseem Kumar,
Jaharul Haque,
Judith Lacoste,
John Hiscott,
Bryan R.G. Williams
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.14.6288
Subject(s) - protein kinase r , biology , rna silencing , microbiology and biotechnology , transcription factor , transcription (linguistics) , phosphorylation , nfkb1 , protein kinase a , rna , gene , mitogen activated protein kinase kinase , biochemistry , rna interference , linguistics , philosophy
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.