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  • Original Article
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PKR; a sentinel kinase for cellular stress

Abstract

The double stranded RNA (dsRNA)-activated protein kinase PKR is a ubiquitously expressed serine/threonine protein kinase that is induced by interferon and activated by dsRNA, cytokine, growth factor and stress signals. It is essential for cells to respond adequately to different stresses including growth factor deprivation, products of the inflammatory response (TNF) and bacterial (lipopolysaccharide) and viral (dsRNA) products. As a vital component of the cellular antiviral response pathway, PKR is autophosphorylated and activated on binding to dsRNA. This results in inhibition of protein synthesis via the phosphorylation of eIF2α and also induces transcription of inflammatory genes by PKR-dependent signaling of the activation of different transcription factors. Along with RNaseL, PKR constitutes the antiviral arm of a group of mammalian stress response proteins that have counterparts in yeast. What began as adaptation to amino acid deprivation and sensing unfolded proteins in the endoplasmic reticulum has evolved into a family of sophisticated mammalian stress response proteins able to mediate cellular responses to both physical and biological stress.

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References

  • Bevilacqua PC and Cech TR. . 1996 Biochemistry 35: 9983–9994.

  • Bevilacqua PC, George CX, Samuel CE and Cech TR. . 1998 Biochemistry 37: 6303–6316.

  • Bycroft M, Grünert S, Murzin AG, Proctor M and St Johnston D. . 1995 EMBO J. 14: 3563–3571.

  • Cai R and Williams BRG. . 1998 J. Biol. Chem. 273: 11274–11280.

  • Carpick BW, Graziano V, Schneider D, Maitra RK, Lee X and Williams BRG. . 1997 J. Biol. Chem. 272: 1291–1296.

  • Chesire JL, Williams BR and Baldwin Jr AS. . 1999 J. Biol. Chem. 274: 4801–4806.

  • Chu W-M, Ballard R, Carpick BW, Williams BRG and Schmid CW. . 1998 Mol. Cell. Biol. 18: 58–68.

  • Clemens MJ and Elia A. . 1997 J. Interferon. Cyto. Res. 17: 503–524.

  • Colthurst DR, Campbell DG and Proud CG. . 1987 Eur. J. Biochem. 166: 357-363.

  • Cosentino GP, Venkatesan S, Serluca FC, Green SR, Mathews MB and Sonenberg N. . 1995 Proc. Natl. Acad. Sci. USA 92: 9445–9449.

  • Cuddihy AR, Wong AH, Tam NW, Li S and Koromilas AE. . 1999a Oncogene 18: 2690–2702.

  • Cuddihy AR, Li S, Wai Ning Tam N, Hoi-Tao Wong A, Taya Y, Abraham N, Bell JC and Korolmilas AE. . 1999b Mol. Cell. Biol. 19: 2475-2484.

  • De Haro C, Méndez R and Santoyo J. . 1996 FASEB J. 10: 1378–1387.

  • Deng X, Ito T, Carr B, Mumby M and May Jr WS. . 1998 J. Biol. Chem. 273: 34157-34163.

  • Der SD, Zhou A, Williams BRG and Silverman RH. . 1997 Proc. Natl. Acad. Sci. USA 94: 3279–3283.

  • DiDonato JA, Hayakawa M, Rothwarf DM, Zandi E and Karin M. . 1997 Nature 388: 548–553.

  • Donze O, Jagus R, Koromilas AE, Hershey JW and Sonenberg N. . 1995 EMBO J. 14: 3828–3834.

  • Gale Jr M and Katze MG. . 1998 Pharmacol. Ther. 78: 29–46.

  • Green SR, Manche L and Mathews MB. . 1995 Mol. Cell. Biol. 15: 358–364.

  • Green SR and Mathews MB. . 1992 Genes Dev. 6: 2478–2490.

  • Haines GK, Cajulis R, Hayden R, Duda R, Talamonti M and Radosevich JL. . 1996 Tumour Biol. 17: 5–12.

  • Harding HP, Zhang Y and Ron D. . 1999 Nature 397: 271–274.

  • Hovanessian AG and Galabru J. . 1987 Eur. J. Biochem. 167: 467–473.

  • Ito T, Jagus R and May WS. . 1994 Proc. Natl. Acad. Sci. USA 91: 7455–7459.

  • Ito T, Yang M and May WS. . 1999 J. Biol. Chem. 274: 15427–15432.

  • Kaufman RJ. . 1999 Genes Dev. 13: 1211–1233.

  • Kharrat A, Macais MJ, Gibson TJ, Nigles M and Pastore A. . 1995 EMBO J. 14: 3572–3584.

  • Kostura M and Mathews M. . 1989 Mol. Cell. Biol. 9: 1576–1586.

  • Kumar A, Commane M, Flickinger TW, Horvath CM and Stark GR. . 1997 Science 278: 1630–1632.

  • Kumar A, Haque J, Lacoste J, Hiscott J and Williams BRG. . 1994 Proc. Natl. Acad. Sci. USA 91: 6288–6292.

  • Kumar KU, Srivastava SP and Kaufman RJ. . 1999 Mol. Cell. Biol. 19: 1116–1125.

  • Lee TG, Tomita J, Hovanessian AG and Katze MG. . 1992 J. Biol. Chem. 267: 14238–14243.

  • Langland JO and Jacobs BL. . 1992 J. Biol. Chem. 267: 10729–10736.

  • Manche L, Green S, Schmedt C and Mathews M. . 1992 Mol. Cell. Biol. 12: 5238–5248.

  • McCormack SJ, Ortega LG, Doohan JP and Samuel CE. . 1994 Virology 198: 92–99.

  • McMillan NAJ, Carpick BW, Hollis B, Toone WM, Zamanian-Daryoush M and Williams BRG. . 1995 J. Biol. Chem. 270: 2601–2606.

  • Mellor H and Proud CG. . 1991 Biochem. Biophys. Res. Comm. 178: 430–437.

  • Melville MW, Tan SL, Wambach M, Song J, Morimoto RI and Katze MG. . 1999 J. Biol. Chem. 274: 37977–37803.

  • Meurs E, Chong K, Galabru J, Thomas NSB, Kerr IM, Williams BRG and Hovanessian AG. . 1990 Cell 62: 379–390.

  • Mundschau LJ and Faller DV. . 1992 J. Biol. Chem. 267: 23092–23098.

  • Mundschau LJ and Faller DV. . 1995 J. Biol. Chem. 270: 3100–3106.

  • Nanduri S, Carpick BW, Yang Y, Williams BRG and Qin J. . 1998 EMBO J. 17: 5458–5465.fc

  • Norris JL and Baldwin Jr AS. . 1999 J. Biol. Chem. 274: 13841–13846.

  • Ortega LG, McCotter MD, Henry GL, McCormack SJ, Thomis DC and Samuel CE. . 1996 Virology 215: 31–39.

  • Pahl HL and Baeuerle PA. . 1997 Trends Biochem. Sci. 22: 63–67.

  • Patel RC and Sen GC. . 1998 EMBO J. 17: 4379–4390.

  • Patel RC, Stanton P, McMillan NAJ, Williams BRG and Sen G. . 1995 J. Biol. Chem. 92: 8283–8287.

  • Patel RC, Stanton P and Sen GC. . 1994 J. Biol. Chem. 269: 18593–18598.

  • Patel RC, Stanton P and Sen GC. . 1996 J. Biol. Chem. 271: 25657–25663.

  • Patel RC, Vestal DJ, Xu Z, Bandyopadhyay S, Guo W, Erme S, Williams BRG and Sen GC. . 1999 J. Biol. Chem., in press.

  • Raveh T, Hovanessian AG, Meurs ER, Sonenberg N and Kimchi A. . 1996 J. Biol. Chem. 271: 25479–25484.

  • Romano PR, Garcia-Barrio MT, Zhang X, Wang Q, Taylor DR, Zhang F, Herring C, Mathews MB, Qin J and Hinnebusch AG. . 1998 Mol. Cell. Biol. 18: 2282–2297.

  • Romano PR, Green SR, Barber GN, Mathews MB and Hinnebusch AG. . 1995 Mol. Cell. Biol. 15: 365–378.

  • Ryter JM and Schultz SC. . 1998 EMBO J. 17: 7505–7513.

  • Savinova O, Joshi B and Jagus R. . 1999 Int. J. Biochem. Cell. Biol. 31: 175–189.

  • Schmidt KN, Traencker Eb, Meier B and Baeuerle PA. . 1995 J. Biol. Chem. 270: 27136–27142.

  • Shang Y, Baumrucker CR and Green MH. . 1998 J. Biol. Chem. 273: 30608–30613.

  • Shimanda A, Shiota G, Miyata H, Kamahora T, Kawasaki H, Shiraki K, Hino S and Terada T. . 1998 Cancer Res. 58: 4434–4438.

  • Silverman RH and Williams BRG. . 1999 Nature 397: 208–211.

  • Srivastava SP, Kumar KU and Kaufman RJ. . 1998 J. Biol. Chem. 273: 2416–2423.

  • St Johnson D, Brown NH, Gall JG and Jantsch M. . 1992 Proc. Natl. Acad. Sci. USA 89: 10979–10983.

  • St Johnston D, Beuchle D and Nüsslein-Volhard C. . 1991 Cell 66: 51–63.

  • Stark GR, Kerr IM, Williams BRG, Silverman RH and Schreiber RD. . 1998 Annu. Rev. Biochem. 67: 227–264.

  • Strong JE, Coffey, MC, Tang D, Sabinin P and Lee PW. . 1998 EMBO J. 17: 3351–3362.

  • Takizawa T, Ohashi K and Nakanishi Y. . 1996 J. Virol. 70: 8128–8132.

  • Tan S-L, Gale Jr MJ and Katze MG. . 1998 Mol. Cell. Biol. 18: 2431–2443.

  • Tan S-L and Katze MG, . 1999 JICR 19: 543–554.

  • Tang NM, Korth MJ, Gale Jr, M, Wambach M, Der SD, Bandyopadhyay SK, Williams BR and Katze MG. . 1999 Mol. Cell. Biol. 19: 4757–4765.

  • Taylor DR, Lee SB, Romano PR, Marshak DR, Hinnebusch AG, Esteban M and Mathews MB. . 1996 Mol. Cell. Biol. 16: 6295–6302.

  • Thomis DC and Samuel CE. . 1993 J. Virol. 67: 7695–7700.

  • Williams BRG. . 1995 Virology 6: 191–202.

  • Wong AHT, Tam NWN, Yang YL, Cuddihy AR, Li SY, Kirchhoff S, Hauser H, Decker T and Koromilas AE. . 1997 EMBO J. 16: 1291–1304.

  • Wu S and Kaufman RJ. . 1996 J. Biol. Chem. 271: 1756–1763.

  • Wu S and Kaufman RJ. . 1997 J. Biol. Chem. 272: 1291–1296.

  • Yeung MC and Lau AS. . 1998 J. Biol. Chem. 273: 25198–25202.

  • Yeung MC, Liu J and Lau AS. . 1996 Proc. Natl. Acad. Sci. USA 93: 12451–12455.

  • Zamanian-Daryoush M, Der S and Williams BRG. . 1999 Oncogene 18: 315–326.

  • Zhou Y, Gobl A, Wang S, Jacobsen MB, Janson ET, Haines GK III, Radosevich JA and Oberg K. . 1998 Eur. J. Cancer 34: 2046–2052.

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Acknowledgements

I thank B Carpick for Figure 1b and R Silverman and KC Goh for comments on the manuscript and helpful discussions.

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Williams, B. PKR; a sentinel kinase for cellular stress. Oncogene 18, 6112–6120 (1999). https://doi.org/10.1038/sj.onc.1203127

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