Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1998 Aug 3;17(15):4379–4390. doi: 10.1093/emboj/17.15.4379

PACT, a protein activator of the interferon-induced protein kinase, PKR.

R C Patel 1, G C Sen 1
PMCID: PMC1170771  PMID: 9687506

Abstract

PKR, a latent protein kinase, mediates the antiviral actions of interferon. It is also involved in cellular signal transduction, apoptosis, growth regulation and differentiation. Although in virus-infected cells, viral double-stranded (ds) RNA can serve as a PKR activator, cellular activators have remained obscure. Here, we report the cloning of PACT, a cellular protein activator of PKR. PACT heterodimerized with PKR and activated it in vitro in the absence of dsRNA. In mammalian cells, overexpression of PACT caused PKR activation and, in yeast, co-expression of PACT enhanced the anti-growth effect of PKR. Thus, PACT has the hallmarks of a direct activator of PKR.

Full Text

The Full Text of this article is available as a PDF (434.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barber G. N., Tomita J., Garfinkel M. S., Meurs E., Hovanessian A., Katze M. G. Detection of protein kinase homologues and viral RNA-binding domains utilizing polyclonal antiserum prepared against a baculovirus-expressed ds RNA-activated 68,000-Da protein kinase. Virology. 1992 Dec;191(2):670–679. doi: 10.1016/0042-6822(92)90242-h. [DOI] [PubMed] [Google Scholar]
  2. Benkirane M., Neuveut C., Chun R. F., Smith S. M., Samuel C. E., Gatignol A., Jeang K. T. Oncogenic potential of TAR RNA binding protein TRBP and its regulatory interaction with RNA-dependent protein kinase PKR. EMBO J. 1997 Feb 3;16(3):611–624. doi: 10.1093/emboj/16.3.611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bushman J. L., Foiani M., Cigan A. M., Paddon C. J., Hinnebusch A. G. Guanine nucleotide exchange factor for eukaryotic translation initiation factor 2 in Saccharomyces cerevisiae: interactions between the essential subunits GCD2, GCD6, and GCD7 and the regulatory subunit GCN3. Mol Cell Biol. 1993 Aug;13(8):4618–4631. doi: 10.1128/mcb.13.8.4618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carpick B. W., Graziano V., Schneider D., Maitra R. K., Lee X., Williams B. R. Characterization of the solution complex between the interferon-induced, double-stranded RNA-activated protein kinase and HIV-I trans-activating region RNA. J Biol Chem. 1997 Apr 4;272(14):9510–9516. doi: 10.1074/jbc.272.14.9510. [DOI] [PubMed] [Google Scholar]
  5. Chong K. L., Feng L., Schappert K., Meurs E., Donahue T. F., Friesen J. D., Hovanessian A. G., Williams B. R. Human p68 kinase exhibits growth suppression in yeast and homology to the translational regulator GCN2. EMBO J. 1992 Apr;11(4):1553–1562. doi: 10.1002/j.1460-2075.1992.tb05200.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Clemens M. J., Elia A. The double-stranded RNA-dependent protein kinase PKR: structure and function. J Interferon Cytokine Res. 1997 Sep;17(9):503–524. doi: 10.1089/jir.1997.17.503. [DOI] [PubMed] [Google Scholar]
  8. Clemens M. J., Laing K. G., Jeffrey I. W., Schofield A., Sharp T. V., Elia A., Matys V., James M. C., Tilleray V. J. Regulation of the interferon-inducible eIF-2 alpha protein kinase by small RNAs. Biochimie. 1994;76(8):770–778. doi: 10.1016/0300-9084(94)90081-7. [DOI] [PubMed] [Google Scholar]
  9. Colthurst D. R., Campbell D. G., Proud C. G. Structure and regulation of eukaryotic initiation factor eIF-2. Sequence of the site in the alpha subunit phosphorylated by the haem-controlled repressor and by the double-stranded RNA-activated inhibitor. Eur J Biochem. 1987 Jul 15;166(2):357–363. doi: 10.1111/j.1432-1033.1987.tb13523.x. [DOI] [PubMed] [Google Scholar]
  10. Cosentino G. P., Venkatesan S., Serluca F. C., Green S. R., Mathews M. B., Sonenberg N. Double-stranded-RNA-dependent protein kinase and TAR RNA-binding protein form homo- and heterodimers in vivo. Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9445–9449. doi: 10.1073/pnas.92.21.9445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Davies M. V., Furtado M., Hershey J. W., Thimmappaya B., Kaufman R. J. Complementation of adenovirus virus-associated RNA I gene deletion by expression of a mutant eukaryotic translation initiation factor. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9163–9167. doi: 10.1073/pnas.86.23.9163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Der S. D., Yang Y. L., Weissmann C., Williams B. R. A double-stranded RNA-activated protein kinase-dependent pathway mediating stress-induced apoptosis. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3279–3283. doi: 10.1073/pnas.94.7.3279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dever T. E., Chen J. J., Barber G. N., Cigan A. M., Feng L., Donahue T. F., London I. M., Katze M. G., Hinnebusch A. G. Mammalian eukaryotic initiation factor 2 alpha kinases functionally substitute for GCN2 protein kinase in the GCN4 translational control mechanism of yeast. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4616–4620. doi: 10.1073/pnas.90.10.4616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Feng G. S., Chong K., Kumar A., Williams B. R. Identification of double-stranded RNA-binding domains in the interferon-induced double-stranded RNA-activated p68 kinase. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5447–5451. doi: 10.1073/pnas.89.12.5447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Galabru J., Hovanessian A. Autophosphorylation of the protein kinase dependent on double-stranded RNA. J Biol Chem. 1987 Nov 15;262(32):15538–15544. [PubMed] [Google Scholar]
  16. Gatignol A., Buckler-White A., Berkhout B., Jeang K. T. Characterization of a human TAR RNA-binding protein that activates the HIV-1 LTR. Science. 1991 Mar 29;251(5001):1597–1600. doi: 10.1126/science.2011739. [DOI] [PubMed] [Google Scholar]
  17. Green S. R., Manche L., Mathews M. B. Two functionally distinct RNA-binding motifs in the regulatory domain of the protein kinase DAI. Mol Cell Biol. 1995 Jan;15(1):358–364. doi: 10.1128/mcb.15.1.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Green S. R., Mathews M. B. Two RNA-binding motifs in the double-stranded RNA-activated protein kinase, DAI. Genes Dev. 1992 Dec;6(12B):2478–2490. doi: 10.1101/gad.6.12b.2478. [DOI] [PubMed] [Google Scholar]
  19. Hershey J. W. Protein phosphorylation controls translation rates. J Biol Chem. 1989 Dec 15;264(35):20823–20826. [PubMed] [Google Scholar]
  20. Hershey J. W. Translational control in mammalian cells. Annu Rev Biochem. 1991;60:717–755. doi: 10.1146/annurev.bi.60.070191.003441. [DOI] [PubMed] [Google Scholar]
  21. Hinnebusch A. G. Gene-specific translational control of the yeast GCN4 gene by phosphorylation of eukaryotic initiation factor 2. Mol Microbiol. 1993 Oct;10(2):215–223. doi: 10.1111/j.1365-2958.1993.tb01947.x. [DOI] [PubMed] [Google Scholar]
  22. Hovanessian A. G., Galabru J. The double-stranded RNA-dependent protein kinase is also activated by heparin. Eur J Biochem. 1987 Sep 15;167(3):467–473. doi: 10.1111/j.1432-1033.1987.tb13360.x. [DOI] [PubMed] [Google Scholar]
  23. Hovanessian A. G. The double stranded RNA-activated protein kinase induced by interferon: dsRNA-PK. J Interferon Res. 1989 Dec;9(6):641–647. doi: 10.1089/jir.1989.9.641. [DOI] [PubMed] [Google Scholar]
  24. Ito T., Jagus R., May W. S. Interleukin 3 stimulates protein synthesis by regulating double-stranded RNA-dependent protein kinase. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7455–7459. doi: 10.1073/pnas.91.16.7455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Judware R., Petryshyn R. Mechanism of action of a cellular inhibitor of the dsRNA-dependent protein kinase from 3T3-F442A cells. J Biol Chem. 1992 Oct 25;267(30):21685–21690. [PubMed] [Google Scholar]
  26. Judware R., Petryshyn R. Partial characterization of a cellular factor that regulates the double-stranded RNA-dependent eIF-2 alpha kinase in 3T3-F442A fibroblasts. Mol Cell Biol. 1991 Jun;11(6):3259–3267. doi: 10.1128/mcb.11.6.3259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Katze M. G. The war against the interferon-induced dsRNA-activated protein kinase: can viruses win? J Interferon Res. 1992 Aug;12(4):241–248. doi: 10.1089/jir.1992.12.241. [DOI] [PubMed] [Google Scholar]
  28. Katze M. G., Wambach M., Wong M. L., Garfinkel M., Meurs E., Chong K., Williams B. R., Hovanessian A. G., Barber G. N. Functional expression and RNA binding analysis of the interferon-induced, double-stranded RNA-activated, 68,000-Mr protein kinase in a cell-free system. Mol Cell Biol. 1991 Nov;11(11):5497–5505. doi: 10.1128/mcb.11.11.5497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kaufman R. J., Davies M. V., Pathak V. K., Hershey J. W. The phosphorylation state of eucaryotic initiation factor 2 alters translational efficiency of specific mRNAs. Mol Cell Biol. 1989 Mar;9(3):946–958. doi: 10.1128/mcb.9.3.946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kaufman R. J., Murtha P. Translational control mediated by eucaryotic initiation factor-2 is restricted to specific mRNAs in transfected cells. Mol Cell Biol. 1987 Apr;7(4):1568–1571. doi: 10.1128/mcb.7.4.1568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kessler S. P., Rowe T. M., Blendy J. A., Erickson R. P., Sen G. C. A cyclic AMP response element in the angiotensin-converting enzyme gene and the transcription factor CREM are required for transcription of the mRNA for the testicular isozyme. J Biol Chem. 1998 Apr 17;273(16):9971–9975. doi: 10.1074/jbc.273.16.9971. [DOI] [PubMed] [Google Scholar]
  32. Kibler K. V., Shors T., Perkins K. B., Zeman C. C., Banaszak M. P., Biesterfeldt J., Langland J. O., Jacobs B. L. Double-stranded RNA is a trigger for apoptosis in vaccinia virus-infected cells. J Virol. 1997 Mar;71(3):1992–2003. doi: 10.1128/jvi.71.3.1992-2003.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Koromilas A. E., Roy S., Barber G. N., Katze M. G., Sonenberg N. Malignant transformation by a mutant of the IFN-inducible dsRNA-dependent protein kinase. Science. 1992 Sep 18;257(5077):1685–1689. doi: 10.1126/science.1382315. [DOI] [PubMed] [Google Scholar]
  34. Kumar A., Yang Y. L., Flati V., Der S., Kadereit S., Deb A., Haque J., Reis L., Weissmann C., Williams B. R. Deficient cytokine signaling in mouse embryo fibroblasts with a targeted deletion in the PKR gene: role of IRF-1 and NF-kappaB. EMBO J. 1997 Jan 15;16(2):406–416. doi: 10.1093/emboj/16.2.406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Lee K., Fajardo M. A., Braun R. E. A testis cytoplasmic RNA-binding protein that has the properties of a translational repressor. Mol Cell Biol. 1996 Jun;16(6):3023–3034. doi: 10.1128/mcb.16.6.3023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Lee S. B., Esteban M. The interferon-induced double-stranded RNA-activated protein kinase induces apoptosis. Virology. 1994 Mar;199(2):491–496. doi: 10.1006/viro.1994.1151. [DOI] [PubMed] [Google Scholar]
  37. Lee S. B., Green S. R., Mathews M. B., Esteban M. Activation of the double-stranded RNA (dsRNA)-activated human protein kinase in vivo in the absence of its dsRNA binding domain. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10551–10555. doi: 10.1073/pnas.91.22.10551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Lengyel P. Tumor-suppressor genes: news about the interferon connection. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5893–5895. doi: 10.1073/pnas.90.13.5893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Leonard G. T., Sen G. C. Restoration of interferon responses of adenovirus E1A-expressing HT1080 cell lines by overexpression of p48 protein. J Virol. 1997 Jul;71(7):5095–5101. doi: 10.1128/jvi.71.7.5095-5101.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Maran A., Maitra R. K., Kumar A., Dong B., Xiao W., Li G., Williams B. R., Torrence P. F., Silverman R. H. Blockage of NF-kappa B signaling by selective ablation of an mRNA target by 2-5A antisense chimeras. Science. 1994 Aug 5;265(5173):789–792. doi: 10.1126/science.7914032. [DOI] [PubMed] [Google Scholar]
  41. Marié I., Blanco J., Rebouillat D., Hovanessian A. G. 69-kDa and 100-kDa isoforms of interferon-induced (2'-5')oligoadenylate synthetase exhibit differential catalytic parameters. Eur J Biochem. 1997 Sep 1;248(2):558–566. doi: 10.1111/j.1432-1033.1997.t01-1-00558.x. [DOI] [PubMed] [Google Scholar]
  42. McCormack S. J., Ortega L. G., Doohan J. P., Samuel C. E. Mechanism of interferon action motif I of the interferon-induced, RNA-dependent protein kinase (PKR) is sufficient to mediate RNA-binding activity. Virology. 1994 Jan;198(1):92–99. doi: 10.1006/viro.1994.1011. [DOI] [PubMed] [Google Scholar]
  43. McCormack S. J., Thomis D. C., Samuel C. E. Mechanism of interferon action: identification of a RNA binding domain within the N-terminal region of the human RNA-dependent P1/eIF-2 alpha protein kinase. Virology. 1992 May;188(1):47–56. doi: 10.1016/0042-6822(92)90733-6. [DOI] [PubMed] [Google Scholar]
  44. McMillan N. A., Carpick B. W., Hollis B., Toone W. M., Zamanian-Daryoush M., Williams B. R. Mutational analysis of the double-stranded RNA (dsRNA) binding domain of the dsRNA-activated protein kinase, PKR. J Biol Chem. 1995 Feb 10;270(6):2601–2606. doi: 10.1074/jbc.270.6.2601. [DOI] [PubMed] [Google Scholar]
  45. Meurs E. F., Galabru J., Barber G. N., Katze M. G., Hovanessian A. G. Tumor suppressor function of the interferon-induced double-stranded RNA-activated protein kinase. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):232–236. doi: 10.1073/pnas.90.1.232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Mundschau L. J., Faller D. V. Endogenous inhibitors of the dsRNA-dependent eIF-2 alpha protein kinase PKR in normal and ras-transformed cells. Biochimie. 1994;76(8):792–800. doi: 10.1016/0300-9084(94)90083-3. [DOI] [PubMed] [Google Scholar]
  47. Mundschau L. J., Faller D. V. Oncogenic ras induces an inhibitor of double-stranded RNA-dependent eukaryotic initiation factor 2 alpha-kinase activation. J Biol Chem. 1992 Nov 15;267(32):23092–23098. [PubMed] [Google Scholar]
  48. Mundschau L. J., Faller D. V. Platelet-derived growth factor signal transduction through the interferon-inducible kinase PKR. Immediate early gene induction. J Biol Chem. 1995 Feb 17;270(7):3100–3106. doi: 10.1074/jbc.270.7.3100. [DOI] [PubMed] [Google Scholar]
  49. Ortega L. G., McCotter M. D., Henry G. L., McCormack S. J., Thomis D. C., Samuel C. E. Mechanism of interferon action. Biochemical and genetic evidence for the intermolecular association of the RNA-dependent protein kinase PKR from human cells. Virology. 1996 Jan 1;215(1):31–39. doi: 10.1006/viro.1996.0004. [DOI] [PubMed] [Google Scholar]
  50. Park H., Davies M. V., Langland J. O., Chang H. W., Nam Y. S., Tartaglia J., Paoletti E., Jacobs B. L., Kaufman R. J., Venkatesan S. TAR RNA-binding protein is an inhibitor of the interferon-induced protein kinase PKR. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4713–4717. doi: 10.1073/pnas.91.11.4713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Patel R. C., Sen G. C. Identification of the double-stranded RNA-binding domain of the human interferon-inducible protein kinase. J Biol Chem. 1992 Apr 15;267(11):7671–7676. [PubMed] [Google Scholar]
  52. Patel R. C., Stanton P., McMillan N. M., Williams B. R., Sen G. C. The interferon-inducible double-stranded RNA-activated protein kinase self-associates in vitro and in vivo. Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8283–8287. doi: 10.1073/pnas.92.18.8283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Patel R. C., Stanton P., Sen G. C. Role of the amino-terminal residues of the interferon-induced protein kinase in its activation by double-stranded RNA and heparin. J Biol Chem. 1994 Jul 15;269(28):18593–18598. [PubMed] [Google Scholar]
  54. Patel R. C., Stanton P., Sen G. C. Specific mutations near the amino terminus of double-stranded RNA-dependent protein kinase (PKR) differentially affect its double-stranded RNA binding and dimerization properties. J Biol Chem. 1996 Oct 11;271(41):25657–25663. doi: 10.1074/jbc.271.41.25657. [DOI] [PubMed] [Google Scholar]
  55. Petryshyn R. A., Ferrenz A. G., Li J. Characterization and mapping of the double-stranded regions involved in activation of PKR within a cellular RNA from 3T3-F442A cells. Nucleic Acids Res. 1997 Jul 1;25(13):2672–2678. doi: 10.1093/nar/25.13.2672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Proud C. G. PKR: a new name and new roles. Trends Biochem Sci. 1995 Jun;20(6):241–246. doi: 10.1016/s0968-0004(00)89025-8. [DOI] [PubMed] [Google Scholar]
  57. Rice A. P., Duncan R., Hershey J. W., Kerr I. M. Double-stranded RNA-dependent protein kinase and 2-5A system are both activated in interferon-treated, encephalomyocarditis virus-infected HeLa cells. J Virol. 1985 Jun;54(3):894–898. doi: 10.1128/jvi.54.3.894-898.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Romano P. R., Green S. R., Barber G. N., Mathews M. B., Hinnebusch A. G. Structural requirements for double-stranded RNA binding, dimerization, and activation of the human eIF-2 alpha kinase DAI in Saccharomyces cerevisiae. Mol Cell Biol. 1995 Jan;15(1):365–378. doi: 10.1128/mcb.15.1.365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Salzberg S., Mandelboim M., Zalcberg M., Shainberg A. Interruption of myogenesis by transforming growth factor beta 1 or EGTA inhibits expression and activity of the myogenic-associated (2'-5') oligoadenylate synthetase and PKR. Exp Cell Res. 1995 Jul;219(1):223–232. doi: 10.1006/excr.1995.1222. [DOI] [PubMed] [Google Scholar]
  60. Samuel C. E., Duncan R., Knutson G. S., Hershey J. W. Mechanism of interferon action. Increased phosphorylation of protein synthesis initiation factor eIF-2 alpha in interferon-treated, reovirus-infected mouse L929 fibroblasts in vitro and in vivo. J Biol Chem. 1984 Nov 10;259(21):13451–13457. [PubMed] [Google Scholar]
  61. Samuel C. E. The eIF-2 alpha protein kinases, regulators of translation in eukaryotes from yeasts to humans. J Biol Chem. 1993 Apr 15;268(11):7603–7606. [PubMed] [Google Scholar]
  62. Sen G. C., Ransohoff R. M. Interferon-induced antiviral actions and their regulation. Adv Virus Res. 1993;42:57–102. doi: 10.1016/s0065-3527(08)60083-4. [DOI] [PubMed] [Google Scholar]
  63. Sikorski R. S., Hieter P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989 May;122(1):19–27. doi: 10.1093/genetics/122.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Sonenberg N. Measures and countermeasures in the modulation of initiation factor activities by viruses. New Biol. 1990 May;2(5):402–409. [PubMed] [Google Scholar]
  65. St Johnston D., Brown N. H., Gall J. G., Jantsch M. A conserved double-stranded RNA-binding domain. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10979–10983. doi: 10.1073/pnas.89.22.10979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Williams B. R. Role of the double-stranded RNA-activated protein kinase (PKR) in cell regulation. Biochem Soc Trans. 1997 May;25(2):509–513. doi: 10.1042/bst0250509. [DOI] [PubMed] [Google Scholar]
  67. Wong A. H., Tam N. W., Yang Y. L., Cuddihy A. R., Li S., Kirchhoff S., Hauser H., Decker T., Koromilas A. E. Physical association between STAT1 and the interferon-inducible protein kinase PKR and implications for interferon and double-stranded RNA signaling pathways. EMBO J. 1997 Mar 17;16(6):1291–1304. doi: 10.1093/emboj/16.6.1291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Wu S., Kaufman R. J. A model for the double-stranded RNA (dsRNA)-dependent dimerization and activation of the dsRNA-activated protein kinase PKR. J Biol Chem. 1997 Jan 10;272(2):1291–1296. doi: 10.1074/jbc.272.2.1291. [DOI] [PubMed] [Google Scholar]
  69. Wu S., Kaufman R. J. Double-stranded (ds) RNA binding and not dimerization correlates with the activation of the dsRNA-dependent protein kinase (PKR). J Biol Chem. 1996 Jan 19;271(3):1756–1763. doi: 10.1074/jbc.271.3.1756. [DOI] [PubMed] [Google Scholar]
  70. Yang Y. L., Reis L. F., Pavlovic J., Aguzzi A., Schäfer R., Kumar A., Williams B. R., Aguet M., Weissmann C. Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase. EMBO J. 1995 Dec 15;14(24):6095–6106. doi: 10.1002/j.1460-2075.1995.tb00300.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Yeung M. C., Liu J., Lau A. S. An essential role for the interferon-inducible, double-stranded RNA-activated protein kinase PKR in the tumor necrosis factor-induced apoptosis in U937 cells. Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12451–12455. doi: 10.1073/pnas.93.22.12451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. de Haro C., Méndez R., Santoyo J. The eIF-2alpha kinases and the control of protein synthesis. FASEB J. 1996 Oct;10(12):1378–1387. doi: 10.1096/fasebj.10.12.8903508. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES