Activation of the I kappa B alpha kinase (IKK) complex by double-stranded RNA-binding defective and catalytic inactive mutants of the interferon-inducible protein kinase PKR

Oncogene
T IshiiA E Koromilas

Abstract

The interferon (IFN)-inducible double stranded (ds) RNA-activated protein kinase PKR plays an important role in protein synthesis by modulating the phosphorylation of the alpha-subunit of eukaryotic initiation fact 2 (eIF-2 alpha). In addition to translational control, PKR has been implicated in several signaling pathways leading to gene transcription. For example, PKR induces I kappa B alpha kinase (IKK) activity and I kappa B alpha phosphorylation leading to the induction of NF-kappa B-mediated gene transcription. Recent findings suggested that NF-kappa B activation by PKR does not require the catalytic activity of the kinase. Here, we provide novel evidence that induction of IKK and NF-kappa B activities proceeds independently of the dsRNA-binding properties of PKR and also verify the kinase-free role of PKR in this process. We also show that the effects of PKR mutants on IKK and NF-kappa B activation are independent of cell transformation but are dependent on the amount of the mutant PKR proteins expressed in cells. These data strongly support an indirect role of PKR in I kappa B alpha phosphorylation by modulating IKK activity through pathways that do not utilize the enzymatic and dsRNA-binding properties of PKR.

References

Jun 27, 1992·Lancet·A S BansalB Mandal
Dec 1, 1992·Genes & Development·S R Green, M B Mathews
Sep 11, 1990·Nucleic Acids Research·S Mizushima, S Nagata
Jan 1, 1991·Annual Review of Biochemistry·J W Hershey
May 1, 1989·Research in Immunology·M W KieranA Israel
Mar 1, 1994·The British Journal of Ophthalmology·P HiscottZ Gregor
Feb 1, 1995·Trends in Microbiology·M G Katze
Nov 15, 1995·Genes & Development·I M VermaS Miyamoto
Jan 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·E F MeursA G Hovanessian
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·S MiyamotoI M Verma
Jul 5, 1994·Proceedings of the National Academy of Sciences of the United States of America·A KumarB R Williams
May 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·T E DeverA G Hinnebusch
Jul 2, 1993·Cell·H BüelerC Weissmann
May 12, 1994·Nature·J M KyriakisJ R Woodgett
Jan 1, 1996·Annual Review of Immunology·A S Baldwin
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·S D DerB R Williams
Jun 2, 1997·The EMBO Journal·G J SchoutenA Zantema
Jun 1, 1997·Postgraduate Medical Journal·M ZakiA Nour el Din
Apr 1, 1997·Seminars in Cancer Biology·I Luque, C Gélinas
Oct 23, 1997·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·M J Clemens, A Elia
Nov 5, 1997·British Dental Journal·J L WilliamsJ C Lowry
Aug 5, 1998·Proceedings of the National Academy of Sciences of the United States of America·M Karin, M Delhase
Oct 6, 1998·Annual Review of Biochemistry·G R StarkR D Schreiber

❮ Previous
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Citations

Feb 19, 2009·Molecular and Cellular Biochemistry·Csaba F László, Shiyong Wu
Apr 23, 2013·Nature Chemical Biology·Erik C HettDeborah T Hung
Jan 22, 2004·Viral Immunology·Sarah A Steer, John A Corbett
Apr 18, 2013·International Journal of Oncology·Tatsuji HanejiHiroyuki Morimoto
May 15, 2010·Future Oncology·Zineb Mounir, Antonis E Koromilas
Mar 17, 2010·Journal of Cellular Physiology·William L BlalockLucio Cocco
Jan 22, 2005·Seminars in Cell & Developmental Biology·Christopher G Proud
Oct 1, 2005·Virus Research·Laura H V G GilRuben O Donis
Mar 8, 2012·Growth Factors·Serge Y Fuchs
Dec 31, 2003·Virology·Donalyn ScheunerRandal J Kaufman
Dec 26, 2001·Science's STKE : Signal Transduction Knowledge Environment·B R Williams
Jan 11, 2007·The Journal of Biological Chemistry·Helen L Eley, Michael J Tisdale
Jan 24, 2019·Annual Review of Immunology·Sun Hur
Aug 11, 2007·American Journal of Respiratory Cell and Molecular Biology·Maciej CabanskiJürgen Lohmeyer
Mar 1, 2003·The Journal of Biological Chemistry·Leonard B MaggiJohn A Corbett
Oct 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rudolf HaaseKlaus Ruckdeschel
Sep 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sita AggarwalBharat B Aggarwal
Jul 5, 2017·Acta Biochimica Et Biophysica Sinica·Haizhou WangChengyu Hu
Nov 13, 2018·Communications Biology·Koji OkamotoJeffrey B Kopp
Jul 10, 2019·Experimental and Therapeutic Medicine·Man ZhangDa-Qing Chen
Apr 12, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Juris A GrasisConstantine D Tsoukas
Jan 9, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sarah A SteerJohn A Corbett
Jan 3, 2021·The FEBS Journal·Evelyn ChukwurahMaria Hatzoglou
Jun 24, 2021·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Thomas KehrerLisa Miorin
Jun 9, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Manuela PiazziWilliam Blalock
Sep 17, 2004·Genes & Development·Matthew S Hayden, Sankar Ghosh

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