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 eIF2alpha 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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When phosphorylated, eIF2α becomes a competitive inhibitor of the 5-subunit guanine nucleotide exchange factor eIF2B, decreasing TC assembly.
“When phosphorylated, eIF2α becomes a competitive inhibitor of the 5-subunit guanine nucleotide exchange factor, eIF2B, and decreasing TC assembly [44, 45] (Fig. 1).”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [44]
Cites
Cuddihy, A. R., Hoi-Tao Wong, A., Wai Ning Tam, N., Li, S., & Koromilas, A. E. (1999) · Oncogene · doi:10.1038/sj.onc.1202620 · Cited by 203 · see citing works
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Janeway, C. A., & Medzhitov, R. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.083001.084359 · Cited by 8,394 · see citing works
Toll-like receptors and innate immunity
Medzhitov, R. (2001) · Nature Reviews Immunology · doi:10.1038/35100529 · Cited by 4,308 · see citing works
The integrated stress response
Pakos‐Zebrucka, K., Koryga, I., Mnich, K., Ljujic, M., Samali, A., & Gorman, A. M. (2016) · The EMBO Reports · doi:10.15252/embr.201642195 · Cited by 2,659 · see citing works
Reinitiation involving upstream ORFs regulates <i>ATF4</i> mRNA translation in mammalian cells
Vattem, K. M., & Wek, R. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400541101 · Cited by 1,696 · see citing works
Regulated necrosis: the expanding network of non-apoptotic cell death pathways
Berghe, T. V., Linkermann, A., Jouan-Lanhouet, S., Walczak, H., & Vandenabeele, P. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3737 · Cited by 1,735 · see citing works
Apoptosis and interferons: role of interferon-stimulated genes as mediators of apoptosis
Chawla-Sarkar, M., Lindner, D. J., Liu, Y.-F., Williams, B. R., Sen, G. C., Silverman, R. H., & Borden, E. C. (2003) · Apoptosis · doi:10.1023/a:1023668705040 · Cited by 829 · see citing works
Self-citationThe dsRNA protein kinase PKR: Virus and cell control
García, M. A., Meurs, E. F., & Esteban, M. (2007) · Biochimie · doi:10.1016/j.biochi.2007.03.001 · Cited by 644 · see citing works
Nucleic acid recognition by the innate immune system
Barbalat, R., Ewald, S. E., Mouchess, M. L., & Barton, G. M. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101340 · Cited by 577 · see citing works
The virus battles: IFN induction of the antiviral state and mechanisms of viral evasion
Levy, D. (2001) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(00)00027-7 · Cited by 428 · see citing works
New frontiers in translational control of the cancer genome
Truitt, M. L., & Ruggero, D. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.27 · Cited by 378 · see citing works
Influenza Virus NS1 Protein Counteracts PKR-Mediated Inhibition of Replication
Bergmann, M., Garcia-Sastre, A., Carnero, E., Pehamberger, H., Wolff, K., Palese, P., & Muster, T. (2000) · Journal of Virology · doi:10.1128/jvi.74.13.6203-6206.2000 · Cited by 362 · see citing works
Talimogene laherparepvec: First in class oncolytic virotherapy
Conry, R. M., Westbrook, B., McKee, S., & Norwood, T. G. (2018) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2017.1412896 · Cited by 335 · see citing works
Chang, R. C. C., Wong, A. K. Y., Ng, H.-K., & Hugon, J. (2002) · NeuroReport · doi:10.1097/00001756-200212200-00011 · Cited by 289 · see citing works
Unterberger, U., Höftberger, R., Gelpi, E., Flicker, H., Budka, H., & Voigtländer, T. (2006) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/01.jnen.0000218445.30535.6f · Cited by 237 · see citing works
Brostrom, M. A., & Brostrom, C. O. (2003) · Cell Calcium · doi:10.1016/s0143-4160(03)00127-1 · Cited by 197 · see citing works
Bettaieb, A., Jiang, J. X., Sasaki, Y., Chao, T.-I., Kiss, Z., Chen, X., Tian, J., Katsuyama, M., Yabe-Nishimura, C., Xi, Y., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.04.009 · Cited by 167 · see citing works
Proud, D., Sanders, S. P., & Wiehler, S. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.7.4637 · Cited by 154 · see citing works
Abnormal T cell signal transduction in systemic lupus erythematosus
Kammer, G. M., Perl, A., Richardson, B. C., & Tsokos, G. C. (2002) · Arthritis & Rheumatism · doi:10.1002/art.10192 · Cited by 139 · see citing works
Juhász, G., Puskás, L. G., Komonyi, O., Érdi, B., Maróy, P., Neufeld, T. P., & Sass, M. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402123 · Cited by 121 · see citing works
PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease
Morel, M., Couturier, J., Lafay‐Chebassier, C., Paccalin, M., & Page, G. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00849.x · Cited by 47 · see citing works
Damjanac, M., Page, G., Ragot, S., Laborie, G., Gil, R., Hugon, J., & Paccalin, M. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00688.x · Cited by 31 · see citing works
- Authors
- Williams, B. R.
- Affiliations
- Cleveland Clinic (US)
- Corresponding author
- Williams, Bryan RG
- ORCID
- Williams, Bryan RG
- Venue
- Oncogene
- Published
- 1999-11-01
- Volume
- 18
- Issue
- 45
- Pages
- 6112-6120
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2047391267
- Cited by
- 820
- References
- 1
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 10 · 2023: 12 · 2022: 6 · 2021: 16 · 2020: 18 · 2019: 20 · 2018: 14 · 2017: 15 · 2016: 20 · 2015: 29 · 2014: 27 · 2013: 33 · 2012: 26
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- PKR, double-stranded RNA-dependent protein kinase, cellular stress response, interferon signaling, eIF2α phosphorylation, protein synthesis inhibition, antiviral response, RNase L, TNF signaling, lipopolysaccharide, transcriptional activation, unfolded protein response, amino acid starvation, serine/threonine kinase
- MeSH terms
- Animals, Gene Expression Regulation, RNA, Double-Stranded, Protein Biosynthesis, Signal Transduction, Tumor Suppressor Protein p53, Apoptosis, Heat-Shock Response, eIF-2 Kinase, Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases
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