PKR-mediated signaling

McKee CM, Fischer FA, Bezbradica JS, Coll RC. PHOrming the inflammasome: phosphorylation is a critical switch in inflammasome signalling. Biochem Soc Trans. 2021 Dec 17;49(6):2495–507. PMID: 34854899; PMCID: PMC8786285.; Zhang M, Li J, Yan H, Huang J, Wang F, Liu T, Zeng L, Zhou F. ISGylation in Innate Antiviral Immunity and Pathogen Defense Responses: A Review. Front Cell Dev Biol. 2021;9():788410. PMID: 34901029; PMCID: PMC8662993.; Cesaro T, Michiels T. Inhibition of PKR by Viruses. Front Microbiol. 2021;12():757238. PMID: 34759908; PMCID: PMC8573351.; Costa-Mattioli M, Walter P. The integrated stress response: From mechanism to disease. Science. 2020 Apr 24;368(6489). PMID: 32327570; PMCID: PMC8997189.; Pizzinga M, Harvey RF, Garland GD, Mordue R, Dezi V, Ramakrishna M, Sfakianos A, Monti M, Mulroney TE, Poyry T, Willis AE. The cell stress response: extreme times call for post-transcriptional measures. Wiley Interdiscip Rev RNA. 2020 May;11(3):e1578. doi: 10.1002/wrna.1578. PMID: 31755249.; Bou-Nader C, Gordon JM, Henderson FE, Zhang J. The search for a PKR code-differential regulation of protein kinase R activity by diverse RNA and protein regulators. RNA. 2019 May;25(5):539–56. PMID: 30770398; PMCID: PMC6467004.; Yim HCH, Williams BRG. Protein Kinase R and the Inflammasome. Journal of Interferon & Cytokine Research. 2014 Jun;34(6):447–54. doi: 10.1089/jir.2014.0008.; Dougherty JD, Reineke LC, Lloyd RE. mRNA Decapping Enzyme 1a (Dcp1a)-induced Translational Arrest through Protein Kinase R (PKR) Activation Requires the N-terminal Enabled Vasodilator-stimulated Protein Homology 1 (EVH1) Domain. Journal of Biological Chemistry. 2014 Feb;289(7):3936–49. doi: 10.1074/jbc.m113.518191.; Marchal JA, Lopez GJ, Peran M, Comino A, Delgado JR, García-García JA, Conde V, Aranda FM, Rivas C, Esteban M, Garcia MA. The impact of PKR activation: from neurodegeneration to cancer. FASEB J. 2014 May;28(5):1965–74. doi: 10.1096/fj.13-248294. PMID: 24522206.; Nallagatla SR, Toroney R, Bevilacqua PC. Regulation of innate immunity through RNA structure and the protein kinase PKR. Current Opinion in Structural Biology. 2011 Feb;21(1):119–27. doi: 10.1016/j.sbi.2010.11.003.; Pindel A, Sadler A. The Role of Protein Kinase R in the Interferon Response. Journal of Interferon & Cytokine Research. 2011 Jan;31(1):59–70. doi: 10.1089/jir.2010.0099.; García MA, Meurs EF, Esteban M. The dsRNA protein kinase PKR: virus and cell control. Biochimie. 2007 Jun;89(6-7):799–811. doi: 10.1016/j.biochi.2007.03.001. PMID: 17451862.; Sadler AJ, Williams BR. Structure and function of the protein kinase R. Curr Top Microbiol Immunol. 2007;316():253–92. doi: 10.1007/978-3-540-71329-6_13. PMID: 17969452.; Fasciano S, Hutchins B, Handy I, Patel RC. Identification of the heparin-binding domains of the interferon-induced protein kinase, PKR. The FEBS Journal. 2005 Mar;272(6):1425–39. doi: 10.1111/j.1742-4658.2005.04575.x.; Tian B, Mathews MB. Functional Characterization of and Cooperation between the Double-stranded RNA-binding Motifs of the Protein Kinase PKR. Journal of Biological Chemistry. 2001 Mar;276(13):9936–44. doi: 10.1074/jbc.m007328200.; Gil J, Esteban M. Induction of apoptosis by the dsRNA-dependent protein kinase (PKR): mechanism of action. Apoptosis. 2000 Apr;5(2):107–14. doi: 10.1023/a:1009664109241. PMID: 11232238.; Patel RC, Sen GC. PACT, a protein activator of the interferon-induced protein kinase, PKR. EMBO J. 1998 Aug 03;17(15):4379–90. PMID: 9687506; PMCID: PMC1170771.; George CX, Thomis DC, McCormack SJ, Svahn CM, Samuel CE. Characterization of the heparin-mediated activation of PKR, the interferon-inducible RNA-dependent protein kinase. Virology. 1996 Jul 01;221(1):180–8. doi: 10.1006/viro.1996.0364. PMID: 8661426.; Kerr IM, Brown RE, Hovanessian AG. Nature of inhibitor of cell-free protein synthesis formed in response to interferon and double-stranded RNA. Nature. 1977 Aug 11;268(5620):540–2. doi: 10.1038/268540a0. PMID: 196217.; Friedman RM, Metz DH, Esteban RM, Tovell DR, Ball LA, Kerr IM. Mechanism of Interferon Action: Inhibition of Viral Messenger Ribonucleic Acid Translation in L-Cell Extracts. J Virol. 1972 Dec;10(6):1184–98. doi: 10.1128/jvi.10.6.1184-1198.1972.

Metabolites



Enzyme

EC Number name full name note
2.7.11.1 non-specific serine/threonine protein kinase ATP:protein phosphotransferase (non-specific)
2.7.11.10 IkappaB kinase ATP:[IkappaB protein] phosphotransferase
2.7.11.22 cyclin-dependent kinase ATP:cyclin phosphotransferase
2.7.11.23 [RNA-polymerase]-subunit kinase ATP:[DNA-directed RNA polymerase] phosphotransferase
2.7.12.2 mitogen-activated protein kinase kinase ATP:protein phosphotransferase (MAPKKK-activated)
3.6.4.13 RNA helicase


Proteins

Protein ID name full name