Double stranded RNA-dependent protein kinase

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Page G, Rioux Bilan A, Ingrand S, Lafay-Chebassier C, Pain S, Perault Pochat MC, Bouras C, Bayer T, Hugon J (2006) Activated double-stranded RNA-dependent protein kinase and neuronal death in models of Alzheimer s disease. Neuroscience 139 1343-1354... 

Xu Z, WUliams BRG (2000) The B56a regulatory subunit of protein phosphatase 2 A is a target for regulation by double-stranded RNA-dependent protein kinase PKR. Mol CeU Biol 20 5285-5299... 

Morimoto, H. et al., Okadaic acid induces apoptosis through double-stranded RNA-dependent protein kinase/eukaryotic initiation factor-2a pathway in human osteoblastic MG63 cells, J. Biochem., 136, 433, 2004. 

Johnson PA, MacLean C, Marsden HS, Dalziel RG, Everett RD (1986) The product of gene USll of herpes simplex virus type 1 is expressed as a true late gene. J Gen Virol 67 871 883 Kerr IM, Brown RE (1978) pppA2 p5 A2 p5 A an inhibitor of protein synthesis synthesized with an enzyme fraction from interferon-treated cells. Proc Natl Acad Sci USA 75 256 260 Khabar KS, Dhalla M, Siddiqui Y, Zhou A, Al-Ahdal MN, Der SD, Silverman RH. Williams BR (2000) Effect of deficiency of the double-stranded RNA-dependent protein kinase, PKR, on antiviral resistance in the presence or absence of ribonuclease L HSV-1 replication is particularly sensitive to deficiency of the major IFN-mediated enzymes [In Process Citation]. J Interferon Cytokine Res 20 653-659... 

Kumar A, Haque J, Lacoste J, Hiscott J, Williams BR (1994) Double-stranded RNA-dependent protein kinase activates transcription factor NF-k B by phosphorylating I kappa B. Proc Natl Acad Sci USA 91 6288-6292... 

Desbarats J, Wade T, Wade WF, Newell MK (1999) Dichotomy between naive and memory CD4( + ) T cell responses to Fas engagement. Proc Natl Acad Sci USA 96 8104-8109 Dimitrov T, Krajcsi P, Hermiston TW, Tollefson AE, Hannink M, Wold WS (1997) Adenovirus E3-10.4K/14.5K protein complex inhibits tumor necrosis factor-induced translocation of cytosolic phospholipase A2 to membranes. J Virol 71 2830-2837 Donze O, Dostie J, Sonenberg N (1999) Regulatable expression of the interferon-induced double-stranded RNA dependent protein kinase PKR induces apoptosis and Fas receptor expression. Virology 256 322-329... 

Ito T, Yang M, May WS. RAX, a cellular aaivator for double-stranded RNA-dependent protein kinase during stress signaling. J Biol Chem 1999 274(22) 15427-15432. 

Romano PR, Zhang F, Tan SL et al. Inhibition of double-stranded RNA-dependent protein kinase PKR by vaccinia virus E3 role of complex formation and the E3 N-terminal domain. Mol Cell Biol 1998 18(12) 7304-7316. 

Yang LFR YL, Pavlovic J, Aguzzi A et al. Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase. EMBO J 1995 14(24) 6095-6106. 

Double-stranded (ds) RNA-dependent protein kinase (PKR) was the first PRR shown to rect ise a product of viral replication, namely dsRNA. PKR is induced by IFN and in a critical host antiviral defence mechanism and as such it is both a PRR and an IFN eflFeaor protein. The discovery of PKR explained the observation that in cells pretreated with IFN, the translation ofviral mRNAs were blocked. - PKR is activated in response to viral, cellular or synthetic dsRNA of 30... 

Fig. 1.56. Control of eIF-2 by phosphorylation. Phosphorylated eIF-2 GDP binds strongly to eIF-2B without nucleotide exchange occurring. Initiation of protein biosynthesis is not possible in this case.In reticulocytes, eIF-2 is subject to phosphorylation by the heme-regulated eIF-2-kinase (HRI). The activity of the dimeric HRI is regulated via the heme concentration. Another protein kinase that can phosphorylate and regulate eIF-2 is the RNA-dependent eIF2a-kinase (PKR). The latter is induced by interferons and activated by double stranded RNA.

Wu, S. and R.J. Kaufman, Double-stranded (ds) RNA binding and not dimerization correlates with the activation of the dsRNA-dependent protein kinase (PKR). J Biol Chem, 1996.271(3) p. 1756-63. 

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