RNA-dependent protein kinase PKR is required for activation of NF-kappa B by IFN-gamma in a STAT1-independent pathway.
作者： Amitabha Deb , S. Jaharul Haque , Trine Mogensen , Robert H. Silverman , Bryan R. G. Williams
DOI: 10.4049/JIMMUNOL.166.10.6170
关键词:
摘要: The IFN-inducible dsRNA-activated protein kinase PKR regulates synthesis through phosphorylation of eukaryotic initiation factor-2alpha. It also acts as a signal transducer for transcription factors NF-kappaB, IFN regulatory factor-1, and activating factor-2. IFN-gamma, pleiotropic cytokine, elicits gene expression by the Janus kinase-STAT signaling pathway. IFN-gamma can synergize with TNF-alpha to activate NF-kappaB in number cell lines. Here we show that alone kinase-1-mediated, but Stat1-independent, mechanism. activation is associated degradation IkappaB beta. response be blocked 2',5'-oligoadenylate-linked antisense chimeras against mRNA. There was no PKR-null cells, indicating required NF-kappaB.
jimmunol.org 参考文章(46)
S. D. Der, Y.-L. Yang, C. Weissmann, B. R. G. Williams, A double-stranded RNA-activated protein kinase-dependent pathway mediating stress-induced apoptosis Proceedings of the National Academy of Sciences of the United States of America. ,vol. 94, pp. 3279- 3283 ,(1997) , 10.1073/PNAS.94.7.3279
Albert S. Baldwin, THE NF-κB AND IκB PROTEINS: New Discoveries and Insights Annual Review of Immunology. ,vol. 14, pp. 649- 681 ,(1996) , 10.1146/ANNUREV.IMMUNOL.14.1.649
B. R. G. Williams, Role of the double-stranded RNA-activated protein kinase (PKR) in cell regulation Biochemical Society Transactions. ,vol. 25, pp. 509- 513 ,(1997) , 10.1042/BST0250509
A. S. Neish, Prokaryotic Regulation of Epithelial Responses by Inhibition of Ikappa B-alpha Ubiquitination Science. ,vol. 289, pp. 1560- 1563 ,(2000) , 10.1126/SCIENCE.289.5484.1560
Y. L. Yang, L. F. Reis, J. Pavlovic, A. Aguzzi, R. Schäfer, A. Kumar, B. R. Williams, M. Aguet, C. Weissmann, Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase. The EMBO Journal. ,vol. 14, pp. 6095- 6106 ,(1995) , 10.1002/J.1460-2075.1995.TB00300.X
PAUL D. DREW, GUIDO FRANZOSO, KEVIN G. BECKER, VINCENT BOURS, LOUISE M. CARLSON, ULRICH SIEBENLIST, KEIKO OZATO, NF kappa B and interferon regulatory factor 1 physically interact and synergistically induce major histocompatibility class I gene expression. Journal of Interferon and Cytokine Research. ,vol. 15, pp. 1037- 1045 ,(1995) , 10.1089/JIR.1995.15.1037
Robert H. Silverman, Beihua Dong, Ratan K. Maitra, Mark R. Player, Paul F. Torrence, Selective RNA cleavage by isolated RNase L activated with 2-5A antisense chimeric oligonucleotides. Methods in Enzymology. ,vol. 313, pp. 522- 533 ,(2000) , 10.1016/S0076-6879(00)13033-2
H Harada, E Takahashi, S Itoh, K Harada, T A Hori, T Taniguchi, Structure and regulation of the human interferon regulatory factor 1 (IRF-1) and IRF-2 genes: implications for a gene network in the interferon system. Molecular and Cellular Biology. ,vol. 14, pp. 1500- 1509 ,(1994) , 10.1128/MCB.14.2.1500
A. Kumar, J. Haque, J. Lacoste, J. Hiscott, B. R. Williams, Double-stranded RNA-dependent protein kinase activates transcription factor NF-kappa B by phosphorylating I kappa B Proceedings of the National Academy of Sciences of the United States of America. ,vol. 91, pp. 6288- 6292 ,(1994) , 10.1073/PNAS.91.14.6288
Rekha C Patel, Ganes C Sen, PACT, a protein activator of the interferon‐induced protein kinase, PKR The EMBO Journal. ,vol. 17, pp. 4379- 4390 ,(1998) , 10.1093/EMBOJ/17.15.4379