The regulation of the protein kinase PKR by RNA - PubMed

Review

The regulation of the protein kinase PKR by RNA

H D Robertson et al. Biochimie. 1996.

Free article

Abstract

A model is presented for the regulation of the double-stranded RNA (dsRNA)-activated mammalian protein kinase PKR, which is involved in protein synthesis inhibition and the antiviral response in cells. A series of previous findings abut PKROs behavior are reviewed, including its effects on translation; the activation of its protein kinase activity; binding sites for PKR on RNA; PKROs protein domains, which include two double-stranded RNA binding motifs (dsRBMs); and the likelihood of PKR dimer formation. The model which emerges to account for many of these observations includes the suggestion that PKR dimers form which are stabilized and rearranged upon binding to dsRNA regions 60 bp or longer. The hypothesis includes protein conformational changes within each member of a PKR dimer bound to dsRNA which re-position an inhibitory polypeptide domain and thus allow kinase activation. Also considered are ways in which PKR interacts with imperfectly duplexed, highly structured RNA molecules.

Similar articles

• Double-stranded (ds) RNA binding and not dimerization correlates with the activation of the dsRNA-dependent protein kinase (PKR).

  Wu S, Kaufman RJ. Wu S, et al. J Biol Chem. 1996 Jan 19;271(3):1756-63. doi: 10.1074/jbc.271.3.1756. J Biol Chem. 1996. PMID: 8576179

• A model for the double-stranded RNA (dsRNA)-dependent dimerization and activation of the dsRNA-activated protein kinase PKR.

  Wu S, Kaufman RJ. Wu S, et al. J Biol Chem. 1997 Jan 10;272(2):1291-6. doi: 10.1074/jbc.272.2.1291. J Biol Chem. 1997. PMID: 8995434

• Activation of the double-stranded RNA (dsRNA)-activated human protein kinase in vivo in the absence of its dsRNA binding domain.

  Lee SB, Green SR, Mathews MB, Esteban M. Lee SB, et al. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10551-5. doi: 10.1073/pnas.91.22.10551. Proc Natl Acad Sci U S A. 1994. PMID: 7937992 Free PMC article.

• Activation of PKR: an open and shut case?

  Cole JL. Cole JL. Trends Biochem Sci. 2007 Feb;32(2):57-62. doi: 10.1016/j.tibs.2006.12.003. Epub 2006 Dec 29. Trends Biochem Sci. 2007. PMID: 17196820 Free PMC article. Review.

• PKR: a new name and new roles.

  Proud CG. Proud CG. Trends Biochem Sci. 1995 Jun;20(6):241-6. doi: 10.1016/s0968-0004(00)89025-8. Trends Biochem Sci. 1995. PMID: 7631421 Review.

Cited by

• Direct participation of Sam68, the 68-kilodalton Src-associated protein in mitosis, in the CRM1-mediated Rev nuclear export pathway.

  Li J, Liu Y, Kim BO, He JJ. Li J, et al. J Virol. 2002 Aug;76(16):8374-82. doi: 10.1128/jvi.76.16.8374-8382.2002. J Virol. 2002. PMID: 12134041 Free PMC article.

• A left-handed RNA double helix bound by the Z alpha domain of the RNA-editing enzyme ADAR1.

  Placido D, Brown BA 2nd, Lowenhaupt K, Rich A, Athanasiadis A. Placido D, et al. Structure. 2007 Apr;15(4):395-404. doi: 10.1016/j.str.2007.03.001. Structure. 2007. PMID: 17437712 Free PMC article.

• Resistance of human hepatitis delta virus RNAs to dicer activity.

  Chang J, Provost P, Taylor JM. Chang J, et al. J Virol. 2003 Nov;77(22):11910-7. doi: 10.1128/jvi.77.22.11910-11917.2003. J Virol. 2003. PMID: 14581527 Free PMC article.

• Viral double-stranded RNAs from vaccinia virus early or intermediate gene transcripts possess PKR activating function, resulting in NF-kappaB activation, when the K1 protein is absent or mutated.

  Willis KL, Langland JO, Shisler JL. Willis KL, et al. J Biol Chem. 2011 Mar 11;286(10):7765-7778. doi: 10.1074/jbc.M110.194704. Epub 2010 Dec 23. J Biol Chem. 2011. PMID: 21183678 Free PMC article.

• The adenovirus VA RNA-derived miRNAs are not essential for lytic virus growth in tissue culture cells.

  Kamel W, Segerman B, Öberg D, Punga T, Akusjärvi G. Kamel W, et al. Nucleic Acids Res. 2013 May;41(9):4802-12. doi: 10.1093/nar/gkt172. Epub 2013 Mar 21. Nucleic Acids Res. 2013. PMID: 23525465 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database