Ribosome targeting of PKR is mediated by two double-stranded RNA-binding domains and facilitates in vivo phosphorylation of eukaryotic initiation factor-2.

The Journal of Biological Chemistry
S ZhuR C Wek

Abstract

Protein kinase PKR is activated in mammalian cells during viral infection, leading to phosphorylation of the alpha subunit of eukaryotic initiation factor-2 (eIF-2alpha) and inhibition of protein synthesis. This antiviral response is thought to be mediated by association of double-stranded RNA (ds-RNA), a by-product of viral replication, with two ds-RNA-binding domains (DRBDs) located in the amino terminus of PKR. Recent studies have observed that expression of mammalian PKR in yeast leads to a slow growth phenotype due to hyperphosphorylation of eIF-2alpha. In this report, we observed that while DRBD sequences are required for PKR to function in the yeast model system, these sequences are not required for in vitro phosphorylation of eIF-2alpha. To explain this apparent contradiction, we proposed that these sequences are required to target the kinase to the translation machinery. Using sucrose gradient sedimentation, we found that wild-type PKR was associated with ribosomes, specifically with 40 S particles. Deletions or residue substitutions in the DRBD sequences blocked kinase interaction with ribosomes. These results indicate that in addition to mediating ds-RNA control of PKR, the DRBD sequences facilitate PKR association w...Continue Reading

References

Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·D C Thomis, C E Samuel
Nov 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·M SchwemmleM Bachmann
Jun 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·G S FengB R Williams
Dec 1, 1992·Genes & Development·S R Green, M B Mathews
Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·D St JohnstonM Jantsch
Jun 1, 1992·Microbiological Reviews·W C Merrick
Jun 1, 1992·Molecular Microbiology·H Yoon, T F Donahue
Jan 1, 1991·Annual Review of Biochemistry·J W Hershey
Jan 1, 1989·Annual Review of Biochemistry·P Cohen
Apr 1, 1989·Molecular and Cellular Biology·M Kostura, M B Mathews
Jan 2, 1989·European Journal of Biochemistry·J GalabruA G Hovanessian
Sep 15, 1987·European Journal of Biochemistry·A G Hovanessian, J Galabru
Aug 29, 1995·Proceedings of the National Academy of Sciences of the United States of America·R C PatelG C Sen
Oct 10, 1995·Proceedings of the National Academy of Sciences of the United States of America·G P CosentinoN Sonenberg
Jan 1, 1995·Annual Review of Biochemistry·D E Draper
Jun 1, 1995·Trends in Biochemical Sciences·R C Prince, G N George
Jun 1, 1995·Trends in Biochemical Sciences·C G Proud
Jan 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·E F MeursA G Hovanessian
Jan 1, 1995·Molecular and Cellular Biology·S R GreenM B Mathews
Nov 1, 1994·Trends in Biochemical Sciences·R C Wek
Jul 5, 1994·Proceedings of the National Academy of Sciences of the United States of America·A KumarB R Williams
Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·S B LeeM Esteban
May 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·T E DeverA G Hinnebusch
May 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·G N BarberM G Katze

❮ Previous
Next ❯

Citations

Jun 17, 1999·FEMS Microbiology Reviews·A W Nicholson
Apr 27, 1999·The International Journal of Biochemistry & Cell Biology·R JagusG N Barber
Jul 27, 2006·Biochemistry·Peter A LemaireJames L Cole
Apr 25, 2001·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·T IwamuraT Fujita
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
May 27, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Hee Kyong Bae, James J Pestka
Jun 7, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Maoxiang Li, James J Pestka
Jul 5, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jennifer S GrayJames J Pestka
Feb 26, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Heekyong BaeJames J Pestka
Sep 22, 2006·Journal of Virology·Morgan HakkiAdam P Geballe
Dec 13, 2006·Microbiology and Molecular Biology Reviews : MMBR·M A GarcíaM Esteban
Jun 6, 2000·Microbiology and Molecular Biology Reviews : MMBR·M GaleM G Katze
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·F AngensteinI J Weiler
Jan 1, 2013·Toxicology Letters·Chanemougasoundharam Arunachalam, Fiona M Doohan
Dec 23, 2009·Progress in Biophysics and Molecular Biology·Krupa DeshmukhNarayanaswamy Srinivasan
Apr 25, 2007·Biochimie·M A GarcíaM Esteban
Jun 30, 2000·Molecular Genetics and Metabolism·Y H XuG A Grabowski
Apr 25, 2006·Biochemical and Biophysical Research Communications·Massimo SquatritoGiulio F Draetta
Mar 5, 2013·Toxicon : Official Journal of the International Society on Toxinology·Kerrie L MayNilgun E Tumer
Jan 15, 2013·Virulence·Muhammad Munir, Mikael Berg
Dec 7, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ewelina GolecBen C King
Mar 18, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Hui-Ren ZhouJames J Pestka
Jan 20, 2001·The Journal of Biological Chemistry·P P RuvoloW S May

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