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Higher-order substrate recognition of eIF2alpha by the RNA-dependent protein kinase PKR.

Dar AC, Dever TE, Sicheri F
Cell 122 887-900 (2005)
Cited: 270 times
EuropePMC logo PMID: 16179258

Abstract

In response to binding viral double-stranded RNA byproducts within a cell, the RNA-dependent protein kinase PKR phosphorylates the alpha subunit of the translation initiation factor eIF2 on a regulatory site, Ser51. This triggers the general shutdown of protein synthesis and inhibition of viral propagation. To understand the basis for substrate recognition by and the regulation of PKR, we determined X-ray crystal structures of the catalytic domain of PKR in complex with eIF2alpha. The structures reveal that eIF2alpha binds to the C-terminal catalytic lobe while catalytic-domain dimerization is mediated by the N-terminal lobe. In addition to inducing a local unfolding of the Ser51 acceptor site in eIF2alpha, its mode of binding to PKR affords the Ser51 site full access to the catalytic cleft of PKR. The generality and implications of the structural mechanisms uncovered for PKR to the larger family of four human eIF2alpha protein kinases are discussed.

Reviews - 2a19 mentioned but not cited (6)

  1. Double-Stranded RNA Sensors and Modulators in Innate Immunity. Hur S. Annu Rev Immunol 37 349-375 (2019)
  2. Substrate and docking interactions in serine/threonine protein kinases. Goldsmith EJ, Akella R, Min X, Zhou T, Humphreys JM. Chem Rev 107 5065-5081 (2007)
  3. Bacteriophage T4 gene 41 helicase and gene 59 helicase-loading protein: a versatile couple with roles in replication and recombination. Jones CE, Mueser TC, Dudas KC, Kreuzer KN, Nossal NG. Proc Natl Acad Sci U S A 98 8312-8318 (2001)
  4. The search for a PKR code-differential regulation of protein kinase R activity by diverse RNA and protein regulators. Bou-Nader C, Gordon JM, Henderson FE, Zhang J. RNA 25 539-556 (2019)
  5. Kinase Atlas: Druggability Analysis of Potential Allosteric Sites in Kinases. Yueh C, Rettenmaier J, Xia B, Hall DR, Alekseenko A, Porter KA, Barkovich K, Keseru G, Whitty A, Wells JA, Vajda S, Kozakov D. J Med Chem 62 6512-6524 (2019)
  6. Functional Interfaces, Biological Pathways, and Regulations of Interferon-Related DNA Damage Resistance Signature (IRDS) Genes. Padariya M, Sznarkowska A, Kote S, Gómez-Herranz M, Mikac S, Pilch M, Alfaro J, Fahraeus R, Hupp T, Kalathiya U. Biomolecules 11 622 (2021)

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  1. Structural mechanism for NEK7-licensed activation of NLRP3 inflammasome. Sharif H, Wang L, Wang WL, Magupalli VG, Andreeva L, Qiao Q, Hauenstein AV, Wu Z, Núñez G, Mao Y, Wu H. Nature 570 338-343 (2019)
  2. Rapid evolution of protein kinase PKR alters sensitivity to viral inhibitors. Rothenburg S, Seo EJ, Gibbs JS, Dever TE, Dittmar K. Nat Struct Mol Biol 16 63-70 (2009)
  3. Assessment of helical interfaces in protein-protein interactions. Jochim AL, Arora PS. Mol Biosyst 5 924-926 (2009)
  4. The structure of the PERK kinase domain suggests the mechanism for its activation. Cui W, Li J, Ron D, Sha B. Acta Crystallogr D Biol Crystallogr 67 423-428 (2011)
  5. Using multiple microenvironments to find similar ligand-binding sites: application to kinase inhibitor binding. Liu T, Altman RB. PLoS Comput Biol 7 e1002326 (2011)
  6. Allosteric activation mechanism of the Mycobacterium tuberculosis receptor Ser/Thr protein kinase, PknB. Lombana TN, Echols N, Good MC, Thomsen ND, Ng HL, Greenstein AE, Falick AM, King DS, Alber T. Structure 18 1667-1677 (2010)
  7. Intracellular eukaryotic parasites have a distinct unfolded protein response. Gosline SJ, Nascimento M, McCall LI, Zilberstein D, Thomas DY, Matlashewski G, Hallett M. PLoS One 6 e19118 (2011)
  8. Activation of protein kinase PKR requires dimerization-induced cis-phosphorylation within the activation loop. Dey M, Mann BR, Anshu A, Mannan MA. J Biol Chem 289 5747-5757 (2014)
  9. Archaeal aIF2B interacts with eukaryotic translation initiation factors eIF2alpha and eIF2Balpha: Implications for aIF2B function and eIF2B regulation. Dev K, Santangelo TJ, Rothenburg S, Neculai D, Dey M, Sicheri F, Dever TE, Reeve JN, Hinnebusch AG. J Mol Biol 392 701-722 (2009)
  10. A machine learning-based chemoproteomic approach to identify drug targets and binding sites in complex proteomes. Piazza I, Beaton N, Bruderer R, Knobloch T, Barbisan C, Chandat L, Sudau A, Siepe I, Rinner O, de Souza N, Picotti P, Reiter L. Nat Commun 11 4200 (2020)
  11. Domain stabilities in protein kinase R (PKR): evidence for weak interdomain interactions. Anderson E, Cole JL. Biochemistry 47 4887-4897 (2008)
  12. Structural Basis of Protein Kinase R Autophosphorylation. Mayo CB, Erlandsen H, Mouser DJ, Feinstein AG, Robinson VL, May ER, Cole JL. Biochemistry 58 2967-2977 (2019)
  13. Dimeric Structure of the Pseudokinase IRAK3 Suggests an Allosteric Mechanism for Negative Regulation. Lange SM, Nelen MI, Cohen P, Kulathu Y. Structure 29 238-251.e4 (2021)
  14. Structural and molecular basis of interaction of HCV non-structural protein 5A with human casein kinase 1α and PKR. Sudha G, Yamunadevi S, Tyagi N, Das S, Srinivasan N. BMC Struct Biol 12 28 (2012)
  15. Identification and validation of novel PERK inhibitors. Wang Q, Park J, Devkota AK, Cho EJ, Dalby KN, Ren P. J Chem Inf Model 54 1467-1475 (2014)
  16. Baculovirus protein PK2 subverts eIF2α kinase function by mimicry of its kinase domain C-lobe. Li JJ, Cao C, Fixsen SM, Young JM, Ono C, Bando H, Elde NC, Katsuma S, Dever TE, Sicheri F. Proc Natl Acad Sci U S A 112 E4364-73 (2015)
  17. The Effectiveness of Dietary Byproduct Antioxidants on Induced CYP Genes Expression and Histological Alteration in Piglets Liver and Kidney Fed with Aflatoxin B1 and Ochratoxin A. Popescu RG, Bulgaru C, Untea A, Vlassa M, Filip M, Hermenean A, Marin D, Țăranu I, Georgescu SE, Dinischiotu A. Toxins (Basel) 13 148 (2021)
  18. Fast and automated functional classification with MED-SuMo: an application on purine-binding proteins. Doppelt-Azeroual O, Delfaud F, Moriaud F, de Brevern AG. Protein Sci 19 847-867 (2010)
  19. Molecular mechanism by which palmitate inhibits PKR autophosphorylation. Cho H, Mukherjee S, Palasuberniam P, Pillow L, Bilgin B, Nezich C, Walton SP, Feig M, Chan C. Biochemistry 50 1110-1119 (2011)
  20. Residues required for phosphorylation of translation initiation factor eIF2α under diverse stress conditions are divergent between yeast and human. Majumder M, Mitchell D, Merkulov S, Wu J, Guan BJ, Snider MD, Krokowski D, Yee VC, Hatzoglou M. Int J Biochem Cell Biol 59 135-141 (2015)
  21. Binding site multiplicity with fatty acid ligands: implications for the regulation of PKR kinase autophosphorylation with palmitate. Fang L, Cho HJ, Chan C, Feig M. Proteins 82 2429-2442 (2014)
  22. Ebola Virus VP35 Protein: Modeling of the Tetrameric Structure and an Analysis of Its Interaction with Human PKR. Banerjee A, Mitra P. J Proteome Res 19 4533-4542 (2020)
  23. Gene expression in a canine basilar artery vasospasm model: a genome-wide network-based analysis. Sasahara A, Kasuya H, Krischek B, Tajima A, Onda H, Sasaki T, Akagawa H, Hori T, Inoue I. Neurosurg Rev 31 283-290 (2008)
  24. Higher-order phosphatase-substrate contacts terminate the integrated stress response. Yan Y, Harding HP, Ron D. Nat Struct Mol Biol 28 835-846 (2021)
  25. Stimulators of translation identified during a small molecule screening campaign. Shin U, Williams DE, Kozakov D, Hall DR, Beglov D, Vajda S, Andersen RJ, Pelletier J. Anal Biochem 447 6-14 (2014)
  26. A postnatal network of co-hepato/pancreatic stem/progenitors in the biliary trees of pigs and humans. Zhang W, Wang X, Lanzoni G, Wauthier E, Simpson S, Ezzell JA, Allen A, Suitt C, Krolik J, Jhirad A, Dominguez-Bendala J, Cardinale V, Alvaro D, Overi D, Gaudio E, Sethupathy P, Carpino G, Adin C, Piedrahita JA, Mathews K, He Z, Reid LM. NPJ Regen Med 8 40 (2023)
  27. DELE1 oligomerization promotes integrated stress response activation. Yang J, Baron KR, Pride DE, Schneemann A, Guo X, Chen W, Song AS, Aviles G, Kampmann M, Luke Wiseman R, Lander GC. Nat Struct Mol Biol 30 1295-1302 (2023)
  28. Discovery and identification of EIF2AK2 as a direct key target of berberine for anti-inflammatory effects. Wei W, Zeng Q, Wang Y, Guo X, Fan T, Li Y, Deng H, Zhao L, Zhang X, Liu Y, Shi Y, Zhu J, Ma X, Wang Y, Jiang J, Song D. Acta Pharm Sin B 13 2138-2151 (2023)
  29. Establishment and Characterization of Immortalized Minipig Neural Stem Cell Line. Choi SS, Yoon SB, Lee SR, Kim SU, Cha YJ, Lee D, Kim SU, Chang KT, Lee HJ. Cell Transplant 26 271-281 (2017)
  30. Ursodeoxycholic Acid Binds PERK and Ameliorates Neurite Atrophy in a Cellular Model of GM2 Gangliosidosis. Morales C, Fernandez M, Ferrer R, Raimunda D, Carrer DC, Bollo M. Int J Mol Sci 24 7209 (2023)


Reviews citing this publication (69)

  1. Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Sonenberg N, Hinnebusch AG. Cell 136 731-745 (2009)
  2. Interferon-inducible antiviral effectors. Sadler AJ, Williams BR. Nat Rev Immunol 8 559-568 (2008)
  3. Classification of intrinsically disordered regions and proteins. van der Lee R, Buljan M, Lang B, Weatheritt RJ, Daughdrill GW, Dunker AK, Fuxreiter M, Gough J, Gsponer J, Jones DT, Kim PM, Kriwacki RW, Oldfield CJ, Pappu RV, Tompa P, Uversky VN, Wright PE, Babu MM. Chem Rev 114 6589-6631 (2014)
  4. Impact of protein kinase PKR in cell biology: from antiviral to antiproliferative action. García MA, Gil J, Ventoso I, Guerra S, Domingo E, Rivas C, Esteban M. Microbiol Mol Biol Rev 70 1032-1060 (2006)
  5. Protein kinases: evolution of dynamic regulatory proteins. Taylor SS, Kornev AP. Trends Biochem Sci 36 65-77 (2011)
  6. The eIF2α kinases: their structures and functions. Donnelly N, Gorman AM, Gupta S, Samali A. Cell Mol Life Sci 70 3493-3511 (2013)
  7. The dsRNA protein kinase PKR: virus and cell control. García MA, Meurs EF, Esteban M. Biochimie 89 799-811 (2007)
  8. Uses for JNK: the many and varied substrates of the c-Jun N-terminal kinases. Bogoyevitch MA, Kobe B. Microbiol Mol Biol Rev 70 1061-1095 (2006)
  9. Rules of engagement: molecular insights from host-virus arms races. Daugherty MD, Malik HS. Annu Rev Genet 46 677-700 (2012)
  10. Regulation of RAF protein kinases in ERK signalling. Lavoie H, Therrien M. Nat Rev Mol Cell Biol 16 281-298 (2015)
  11. The structural basis for control of eukaryotic protein kinases. Endicott JA, Noble ME, Johnson LN. Annu Rev Biochem 81 587-613 (2012)
  12. Eukaryote-like serine/threonine kinases and phosphatases in bacteria. Pereira SF, Goss L, Dworkin J. Microbiol Mol Biol Rev 75 192-212 (2011)
  13. Translational control and the unfolded protein response. Wek RC, Cavener DR. Antioxid Redox Signal 9 2357-2371 (2007)
  14. Keeping the eIF2 alpha kinase Gcn2 in check. Castilho BA, Shanmugam R, Silva RC, Ramesh R, Himme BM, Sattlegger E. Biochim Biophys Acta 1843 1948-1968 (2014)
  15. New modes of translational control in development, behavior, and disease. Sonenberg N, Hinnebusch AG. Mol Cell 28 721-729 (2007)
  16. Structural basis of the unfolded protein response. Korennykh A, Walter P. Annu Rev Cell Dev Biol 28 251-277 (2012)
  17. The evolutionary conundrum of pathogen mimicry. Elde NC, Malik HS. Nat Rev Microbiol 7 787-797 (2009)
  18. Dynamics-Driven Allostery in Protein Kinases. Kornev AP, Taylor SS. Trends Biochem Sci 40 628-647 (2015)
  19. The role of protein kinase R in the interferon response. Pindel A, Sadler A. J Interferon Cytokine Res 31 59-70 (2011)
  20. PKR: A Kinase to Remember. Gal-Ben-Ari S, Barrera I, Ehrlich M, Rosenblum K. Front Mol Neurosci 11 480 (2018)
  21. Eukaryotic cold shock domain proteins: highly versatile regulators of gene expression. Mihailovich M, Militti C, Gabaldón T, Gebauer F. Bioessays 32 109-118 (2010)
  22. The expanding role of NLRs in antiviral immunity. Lupfer C, Kanneganti TD. Immunol Rev 255 13-24 (2013)
  23. dsRNA-dependent protein kinase PKR and its role in stress, signaling and HCV infection. Dabo S, Meurs EF. Viruses 4 2598-2635 (2012)
  24. Activation of PKR: an open and shut case? Cole JL. Trends Biochem Sci 32 57-62 (2007)
  25. Pseudokinases-remnants of evolution or key allosteric regulators? Zeqiraj E, van Aalten DM. Curr Opin Struct Biol 20 772-781 (2010)
  26. PKR and eIF2alpha: integration of kinase dimerization, activation, and substrate docking. Taylor SS, Haste NM, Ghosh G. Cell 122 823-825 (2005)
  27. Regulation of innate immunity through RNA structure and the protein kinase PKR. Nallagatla SR, Toroney R, Bevilacqua PC. Curr Opin Struct Biol 21 119-127 (2011)
  28. ADAR1: "Editor-in-Chief" of Cytoplasmic Innate Immunity. Lamers MM, van den Hoogen BG, Haagmans BL. Front Immunol 10 1763 (2019)
  29. Homing in: Mechanisms of Substrate Targeting by Protein Kinases. Miller CJ, Turk BE. Trends Biochem Sci 43 380-394 (2018)
  30. Protein-protein interactions in the allosteric regulation of protein kinases. Pellicena P, Kuriyan J. Curr Opin Struct Biol 16 702-709 (2006)
  31. Endoplasmic reticulum stress response in yeast and humans. Wu H, Ng BS, Thibault G. Biosci Rep 34 e00118 (2014)
  32. Networks for the allosteric control of protein kinases. Shi Z, Resing KA, Ahn NG. Curr Opin Struct Biol 16 686-692 (2006)
  33. Eukaryotic and archaeal translation initiation factor 2: a heterotrimeric tRNA carrier. Schmitt E, Naveau M, Mechulam Y. FEBS Lett 584 405-412 (2010)
  34. Dance with the Devil: Stress Granules and Signaling in Antiviral Responses. Eiermann N, Haneke K, Sun Z, Stoecklin G, Ruggieri A. Viruses 12 E984 (2020)
  35. Cytochrome P450 regulation: the interplay between its heme and apoprotein moieties in synthesis, assembly, repair, and disposal. Correia MA, Sinclair PR, De Matteis F. Drug Metab Rev 43 1-26 (2011)
  36. Regulation of translation initiation factor eIF2B at the hub of the integrated stress response. Pavitt GD. Wiley Interdiscip Rev RNA 9 e1491 (2018)
  37. Structure and dynamics of PKA signaling proteins. Kim C, Vigil D, Anand G, Taylor SS. Eur J Cell Biol 85 651-654 (2006)
  38. Revisiting protein kinase-substrate interactions: Toward therapeutic development. de Oliveira PS, Ferraz FA, Pena DA, Pramio DT, Morais FA, Schechtman D. Sci Signal 9 re3 (2016)
  39. Evolution of domain combinations in protein kinases and its implications for functional diversity. Deshmukh K, Anamika K, Srinivasan N. Prog Biophys Mol Biol 102 1-15 (2010)
  40. Perception of double-stranded RNA in plant antiviral immunity. Niehl A, Heinlein M. Mol Plant Pathol 20 1203-1210 (2019)
  41. Viral proteins targeting host protein kinase R to evade an innate immune response: a mini review. Dzananovic E, McKenna SA, Patel TR. Biotechnol Genet Eng Rev 34 33-59 (2018)
  42. Control of oncogenesis by eIF2α phosphorylation: implications in PTEN and PI3K-Akt signaling and tumor treatment. Koromilas AE, Mounir Z. Future Oncol 9 1005-1015 (2013)
  43. A tale of two proteins: PACT and PKR and their roles in inflammation. Chukwurah E, Farabaugh KT, Guan BJ, Ramakrishnan P, Hatzoglou M. FEBS J 288 6365-6391 (2021)
  44. Type I Interferon at the Interface of Antiviral Immunity and Immune Regulation: The Curious Case of HIV-1. Boasso A. Scientifica (Cairo) 2013 580968 (2013)
  45. Avian Pattern Recognition Receptor Sensing and Signaling. Neerukonda SN, Katneni U. Vet Sci 7 E14 (2020)
  46. Going for broke: targeting the human cancer pseudokinome. Bailey FP, Byrne DP, McSkimming D, Kannan N, Eyers PA. Biochem J 465 195-211 (2015)
  47. Human Cytomegalovirus Strategies to Maintain and Promote mRNA Translation. Vincent HA, Ziehr B, Moorman NJ. Viruses 8 97 (2016)
  48. Stress Beyond Translation: Poxviruses and More. Liem J, Liu J. Viruses 8 E169 (2016)
  49. Role of the unfolded protein response in determining the fate of tumor cells and the promise of multi-targeted therapies. Shen K, Johnson DW, Vesey DA, McGuckin MA, Gobe GC. Cell Stress Chaperones 23 317-334 (2018)
  50. Eukaryotic type translation initiation factor 2: structure-functional aspects. Stolboushkina EA, Garber MB. Biochemistry (Mosc) 76 283-294 (2011)
  51. Cytoplasmic RNA sensors and their interplay with RNA-binding partners in innate antiviral response: theme and variations. Chan CP, Jin DY. RNA 28 449-477 (2022)
  52. Emerging roles of the αC-β4 loop in protein kinase structure, function, evolution, and disease. Yeung W, Ruan Z, Kannan N. IUBMB Life 72 1189-1202 (2020)
  53. Cellular origins of dsRNA, their recognition and consequences. Chen YG, Hur S. Nat Rev Mol Cell Biol 23 286-301 (2022)
  54. The structural and functional workings of KEOPS. Beenstock J, Sicheri F. Nucleic Acids Res 49 10818-10834 (2021)
  55. Tumor genotype determines susceptibility to oncolytic herpes simplex virus mutants: strategies for clinical application. Smith KD, Shao MY, Posner MC, Weichselbaum RR. Future Oncol 3 545-556 (2007)
  56. ADARs, RNA editing and more in hematological malignancies. Teoh PJ, Koh MY, Chng WJ. Leukemia 35 346-359 (2021)
  57. Orchestration of the activation of protein kinase R by the RNA-binding motif. Sadler AJ. J Interferon Cytokine Res 30 195-204 (2010)
  58. Adaptability in protein structures: structural dynamics and implications in ligand design. Maity A, Majumdar S, Priya P, De P, Saha S, Ghosh Dastidar S. J Biomol Struct Dyn 33 298-321 (2015)
  59. Mammalian and Avian Host Cell Influenza A Restriction Factors. McKellar J, Rebendenne A, Wencker M, Moncorgé O, Goujon C. Viruses 13 522 (2021)
  60. Proteostasis Perturbations and Their Roles in Causing Sterile Inflammation and Autoinflammatory Diseases. Papendorf JJ, Krüger E, Ebstein F. Cells 11 1422 (2022)
  61. Surviving and Adapting to Stress: Translational Control and the Integrated Stress Response. Wek RC, Anthony TG, Staschke KA. Antioxid Redox Signal 39 351-373 (2023)
  62. Use of IFN-Based Biotherapeutics to Harness the Host Against Foot-And-Mouth Disease. Medina GN, de Los Santos T, Diaz-San Segundo F. Front Vet Sci 7 465 (2020)
  63. Mechanism of herpesvirus protein kinase UL13 in immune escape and viral replication. Zhou L, Cheng A, Wang M, Wu Y, Yang Q, Tian B, Ou X, Sun D, Zhang S, Mao S, Zhao XX, Huang J, Gao Q, Zhu D, Jia R, Liu M, Chen S. Front Immunol 13 1088690 (2022)
  64. Activation of cytosolic RNA sensors by endogenous ligands: roles in disease pathogenesis. Straub S, Sampaio NG. Front Immunol 14 1092790 (2023)
  65. Antagonism of Protein Kinase R by Large DNA Viruses. Olson AT, Child SJ, Geballe AP. Pathogens 11 790 (2022)
  66. Getting the message in protein synthesis. Keystone Symposium on Translational Regulatory Mechanisms. Costa-Mattioli M, Bidinosti M, Dever TE. EMBO Rep 9 954-959 (2008)
  67. Inhibition of RNA-binding proteins with small molecules. Wu P. Nat Rev Chem 4 441-458 (2020)
  68. Integration of O-GlcNAc into Stress Response Pathways. Fahie KMM, Papanicolaou KN, Zachara NE. Cells 11 3509 (2022)
  69. Protection of eIF2B from inhibitory phosphorylated eIF2: A viral strategy to maintain mRNA translation during the PKR-triggered integrated stress response. Ito T, Wuerth JD, Weber F. J Biol Chem 299 105287 (2023)

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  1. Systematic discovery of in vivo phosphorylation networks. Linding R, Jensen LJ, Ostheimer GJ, van Vugt MA, Jørgensen C, Miron IM, Diella F, Colwill K, Taylor L, Elder K, Metalnikov P, Nguyen V, Pasculescu A, Jin J, Park JG, Samson LD, Woodgett JR, Russell RB, Russell RB, Bork P, Yaffe MB, Pawson T. Cell 129 1415-1426 (2007)
  2. Novel role of PKR in inflammasome activation and HMGB1 release. Lu B, Nakamura T, Inouye K, Li J, Tang Y, Lundbäck P, Valdes-Ferrer SI, Olofsson PS, Kalb T, Roth J, Zou Y, Erlandsson-Harris H, Yang H, Ting JP, Wang H, Andersson U, Antoine DJ, Chavan SS, Hotamisligil GS, Tracey KJ. Nature 488 670-674 (2012)
  3. A dimerization-dependent mechanism drives RAF catalytic activation. Rajakulendran T, Sahmi M, Lefrançois M, Sicheri F, Therrien M. Nature 461 542-545 (2009)
  4. Mechanistic link between PKR dimerization, autophosphorylation, and eIF2alpha substrate recognition. Dey M, Cao C, Dar AC, Tamura T, Ozato K, Sicheri F, Dever TE. Cell 122 901-913 (2005)
  5. Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation. Zeqiraj E, Filippi BM, Deak M, Alessi DR, van Aalten DM. Science 326 1707-1711 (2009)
  6. Structural and functional diversity of the microbial kinome. Kannan N, Taylor SS, Zhai Y, Venter JC, Manning G. PLoS Biol 5 e17 (2007)
  7. Cytoplasmic STAT3 represses autophagy by inhibiting PKR activity. Shen S, Niso-Santano M, Adjemian S, Takehara T, Malik SA, Minoux H, Souquere S, Mariño G, Lachkar S, Senovilla L, Galluzzi L, Kepp O, Pierron G, Maiuri MC, Hikita H, Kroemer R, Kroemer G. Mol Cell 48 667-680 (2012)
  8. 5'-triphosphate-dependent activation of PKR by RNAs with short stem-loops. Nallagatla SR, Hwang J, Toroney R, Zheng X, Cameron CE, Bevilacqua PC. Science 318 1455-1458 (2007)
  9. Protein kinase R reveals an evolutionary model for defeating viral mimicry. Elde NC, Child SJ, Geballe AP, Malik HS. Nature 457 485-489 (2009)
  10. West Nile virus differentially modulates the unfolded protein response to facilitate replication and immune evasion. Ambrose RL, Mackenzie JM. J Virol 85 2723-2732 (2011)
  11. The pseudoactive site of ILK is essential for its binding to alpha-Parvin and localization to focal adhesions. Fukuda K, Gupta S, Chen K, Wu C, Qin J. Mol Cell 36 819-830 (2009)
  12. Mechanism of PKR Activation by dsRNA. Lemaire PA, Anderson E, Lary J, Cole JL. J Mol Biol 381 351-360 (2008)
  13. Dynamic architecture of a protein kinase. McClendon CL, Kornev AP, Gilson MK, Taylor SS. Proc Natl Acad Sci U S A 111 E4623-31 (2014)
  14. Inhibitors that stabilize a closed RAF kinase domain conformation induce dimerization. Lavoie H, Thevakumaran N, Gavory G, Li JJ, Padeganeh A, Guiral S, Duchaine J, Mao DY, Bouvier M, Sicheri F, Therrien M. Nat Chem Biol 9 428-436 (2013)
  15. Binding and nuclear relocalization of protein kinase R by human cytomegalovirus TRS1. Hakki M, Marshall EE, De Niro KL, Geballe AP. J Virol 80 11817-11826 (2006)
  16. The Plasmodium eukaryotic initiation factor-2alpha kinase IK2 controls the latency of sporozoites in the mosquito salivary glands. Zhang M, Fennell C, Ranford-Cartwright L, Sakthivel R, Gueirard P, Meister S, Caspi A, Doerig C, Nussenzweig RS, Tuteja R, Sullivan WJ, Roos DS, Fontoura BM, Ménard R, Winzeler EA, Nussenzweig V. J Exp Med 207 1465-1474 (2010)
  17. Hepatitis C virus controls interferon production through PKR activation. Arnaud N, Dabo S, Maillard P, Budkowska A, Kalliampakou KI, Mavromara P, Garcin D, Hugon J, Gatignol A, Akazawa D, Wakita T, Meurs EF. PLoS One 5 e10575 (2010)
  18. Translation regulation by eukaryotic initiation factor-2 kinases in the development of latent cysts in Toxoplasma gondii. Narasimhan J, Joyce BR, Naguleswaran A, Smith AT, Livingston MR, Dixon SE, Coppens I, Wek RC, Sullivan WJ. J Biol Chem 283 16591-16601 (2008)
  19. Dimeric structure of pseudokinase RNase L bound to 2-5A reveals a basis for interferon-induced antiviral activity. Huang H, Zeqiraj E, Dong B, Jha BK, Duffy NM, Orlicky S, Thevakumaran N, Talukdar M, Pillon MC, Ceccarelli DF, Wan LC, Juang YC, Mao DY, Gaughan C, Brinton MA, Perelygin AA, Kourinov I, Guarné A, Silverman RH, Sicheri F. Mol Cell 53 221-234 (2014)
  20. Molecular basis for PKR activation by PACT or dsRNA. Li S, Peters GA, Ding K, Zhang X, Qin J, Sen GC. Proc Natl Acad Sci U S A 103 10005-10010 (2006)
  21. A sliding docking interaction is essential for sequential and processive phosphorylation of an SR protein by SRPK1. Ngo JC, Giang K, Chakrabarti S, Ma CT, Huynh N, Hagopian JC, Dorrestein PC, Fu XD, Adams JA, Ghosh G. Mol Cell 29 563-576 (2008)
  22. Activation of the Antiviral Kinase PKR and Viral Countermeasures. Dauber B, Wolff T. Viruses 1 523-544 (2009)
  23. Atomic structure of the KEOPS complex: an ancient protein kinase-containing molecular machine. Mao DY, Neculai D, Downey M, Orlicky S, Haffani YZ, Ceccarelli DF, Ho JS, Szilard RK, Zhang W, Ho CS, Wan L, Fares C, Rumpel S, Kurinov I, Arrowsmith CH, Durocher D, Sicheri F. Mol Cell 32 259-275 (2008)
  24. The structural basis of translational control by eIF2 phosphorylation. Adomavicius T, Guaita M, Zhou Y, Jennings MD, Latif Z, Roseman AM, Pavitt GD. Nat Commun 10 2136 (2019)
  25. A dimeric kinase assembly underlying autophosphorylation in the p21 activated kinases. Pirruccello M, Sondermann H, Pelton JG, Pellicena P, Hoelz A, Chernoff J, Wemmer DE, Kuriyan J. J Mol Biol 361 312-326 (2006)
  26. RNA dimerization promotes PKR dimerization and activation. Heinicke LA, Wong CJ, Lary J, Nallagatla SR, Diegelman-Parente A, Zheng X, Cole JL, Bevilacqua PC. J Mol Biol 390 319-338 (2009)
  27. Elucidation of the heme binding site of heme-regulated eukaryotic initiation factor 2alpha kinase and the role of the regulatory motif in heme sensing by spectroscopic and catalytic studies of mutant proteins. Igarashi J, Murase M, Iizuka A, Pichierri F, Martinkova M, Shimizu T. J Biol Chem 283 18782-18791 (2008)
  28. PfeIK1, a eukaryotic initiation factor 2alpha kinase of the human malaria parasite Plasmodium falciparum, regulates stress-response to amino-acid starvation. Fennell C, Babbitt S, Russo I, Wilkes J, Ranford-Cartwright L, Goldberg DE, Doerig C. Malar J 8 99 (2009)
  29. Auto-activation mechanism of the Mycobacterium tuberculosis PknB receptor Ser/Thr kinase. Mieczkowski C, Iavarone AT, Alber T. EMBO J 27 3186-3197 (2008)
  30. Congenital disease SNPs target lineage specific structural elements in protein kinases. Torkamani A, Kannan N, Taylor SS, Schork NJ. Proc Natl Acad Sci U S A 105 9011-9016 (2008)
  31. The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria. Wehenkel A, Fernandez P, Bellinzoni M, Catherinot V, Barilone N, Labesse G, Jackson M, Alzari PM. FEBS Lett 580 3018-3022 (2006)
  32. Tyrosine phosphorylation acts as a molecular switch to full-scale activation of the eIF2alpha RNA-dependent protein kinase. Su Q, Wang S, Baltzis D, Qu LK, Wong AH, Koromilas AE. Proc Natl Acad Sci U S A 103 63-68 (2006)
  33. Novel membrane-bound eIF2alpha kinase in the flagellar pocket of Trypanosoma brucei. Moraes MC, Jesus TC, Hashimoto NN, Dey M, Schwartz KJ, Alves VS, Avila CC, Bangs JD, Dever TE, Schenkman S, Castilho BA. Eukaryot Cell 6 1979-1991 (2007)
  34. Double-stranded RNA-activated protein kinase PKR of fishes and amphibians: varying the number of double-stranded RNA binding domains and lineage-specific duplications. Rothenburg S, Deigendesch N, Dey M, Dever TE, Tazi L. BMC Biol 6 12 (2008)
  35. The N-terminus of PKR is responsible for the activation of the NF-kappaB signaling pathway by interacting with the IKK complex. Bonnet MC, Daurat C, Ottone C, Meurs EF. Cell Signal 18 1865-1875 (2006)
  36. Structure of PINK1 in complex with its substrate ubiquitin. Schubert AF, Gladkova C, Pardon E, Wagstaff JL, Freund SMV, Steyaert J, Maslen SL, Komander D. Nature 552 51-56 (2017)
  37. Controlling activation of the RNA-dependent protein kinase by siRNAs using site-specific chemical modification. Puthenveetil S, Whitby L, Ren J, Kelnar K, Krebs JF, Beal PA. Nucleic Acids Res 34 4900-4911 (2006)
  38. Evolution of protein binding modes in homooligomers. Dayhoff JE, Shoemaker BA, Bryant SH, Panchenko AR. J Mol Biol 395 860-870 (2010)
  39. Promastigote to amastigote differentiation of Leishmania is markedly delayed in the absence of PERK eIF2alpha kinase-dependent eIF2alpha phosphorylation. Chow C, Cloutier S, Dumas C, Chou MN, Papadopoulou B. Cell Microbiol 13 1059-1077 (2011)
  40. Cofactor-mediated conformational control in the bifunctional kinase/RNase Ire1. Korennykh AV, Egea PF, Korostelev AA, Finer-Moore J, Stroud RM, Zhang C, Shokat KM, Walter P. BMC Biol 9 48 (2011)
  41. An eIF2α-binding motif in protein phosphatase 1 subunit GADD34 and its viral orthologs is required to promote dephosphorylation of eIF2α. Rojas M, Vasconcelos G, Dever TE. Proc Natl Acad Sci U S A 112 E3466-75 (2015)
  42. Mechanism of multi-site phosphorylation from a ROCK-I:RhoE complex structure. Komander D, Garg R, Wan PT, Ridley AJ, Barford D. EMBO J 27 3175-3185 (2008)
  43. A new mechanism of interferon's antiviral action: Induction of autophagy, essential for paramyxovirus replication, is inhibited by the interferon stimulated gene, TDRD7. Subramanian G, Kuzmanovic T, Zhang Y, Peter CB, Veleeparambil M, Chakravarti R, Sen GC, Chattopadhyay S. PLoS Pathog 14 e1006877 (2018)
  44. Interferon-α (IFN-α) suppresses HTLV-1 gene expression and cell cycling, while IFN-α combined with zidovudine induces p53 signaling and apoptosis in HTLV-1-infected cells. Kinpara S, Kijiyama M, Takamori A, Hasegawa A, Sasada A, Masuda T, Tanaka Y, Utsunomiya A, Kannagi M. Retrovirology 10 52 (2013)
  45. Reconstitution and characterization of eukaryotic N6-threonylcarbamoylation of tRNA using a minimal enzyme system. Wan LC, Mao DY, Neculai D, Strecker J, Chiovitti D, Kurinov I, Poda G, Thevakumaran N, Yuan F, Szilard RK, Lissina E, Nislow C, Caudy AA, Durocher D, Sicheri F. Nucleic Acids Res 41 6332-6346 (2013)
  46. Regulation of the p38 mitogen-activated protein kinase and dual-specificity phosphatase 1 feedback loop modulates the induction of interleukin 6 and 8 in cells infected with coronavirus infectious bronchitis virus. Liao Y, Wang X, Huang M, Tam JP, Liu DX. Virology 420 106-116 (2011)
  47. A conserved dimer and global conformational changes in the structure of apo-PknE Ser/Thr protein kinase from Mycobacterium tuberculosis. Gay LM, Ng HL, Alber T. J Mol Biol 360 409-420 (2006)
  48. Structure of the bifunctional isocitrate dehydrogenase kinase/phosphatase. Zheng J, Jia Z. Nature 465 961-965 (2010)
  49. Cooperative roles of fish protein kinase containing Z-DNA binding domains and double-stranded RNA-dependent protein kinase in interferon-mediated antiviral response. Liu TK, Zhang YB, Liu Y, Sun F, Gui JF. J Virol 85 12769-12780 (2011)
  50. Mitogen-activated protein kinases interacting kinases are autoinhibited by a reprogrammed activation segment. Jauch R, Cho MK, Jäkel S, Netter C, Schreiter K, Aicher B, Zweckstetter M, Jäckle H, Wahl MC. EMBO J 25 4020-4032 (2006)
  51. Structure and mode of action of microplusin, a copper II-chelating antimicrobial peptide from the cattle tick Rhipicephalus (Boophilus) microplus. Silva FD, Rezende CA, Rossi DC, Esteves E, Dyszy FH, Schreier S, Gueiros-Filho F, Campos CB, Pires JR, Daffre S. J Biol Chem 284 34735-34746 (2009)
  52. Viral dsRNA inhibitors prevent self-association and autophosphorylation of PKR. McKenna SA, Lindhout DA, Shimoike T, Aitken CE, Puglisi JD. J Mol Biol 372 103-113 (2007)
  53. Crystal structure of the catalytic domain of Haspin, an atypical kinase implicated in chromatin organization. Villa F, Capasso P, Tortorici M, Forneris F, de Marco A, Mattevi A, Musacchio A. Proc Natl Acad Sci U S A 106 20204-20209 (2009)
  54. Conserved intermolecular salt bridge required for activation of protein kinases PKR, GCN2, and PERK. Dey M, Cao C, Sicheri F, Dever TE. J Biol Chem 282 6653-6660 (2007)
  55. Analysis of PKR structure by small-angle scattering. VanOudenhove J, Anderson E, Krueger S, Cole JL. J Mol Biol 387 910-920 (2009)
  56. Mechanistic basis of Nek7 activation through Nek9 binding and induced dimerization. Haq T, Richards MW, Burgess SG, Gallego P, Yeoh S, O'Regan L, Reverter D, Roig J, Fry AM, Bayliss R. Nat Commun 6 8771 (2015)
  57. Myxoma virus M156 is a specific inhibitor of rabbit PKR but contains a loss-of-function mutation in Australian virus isolates. Peng C, Haller SL, Rahman MM, McFadden G, Rothenburg S. Proc Natl Acad Sci U S A 113 3855-3860 (2016)
  58. Evidence that eukaryotic translation elongation factor 1A (eEF1A) binds the Gcn2 protein C terminus and inhibits Gcn2 activity. Visweswaraiah J, Lageix S, Castilho BA, Izotova L, Kinzy TG, Hinnebusch AG, Sattlegger E. J Biol Chem 286 36568-36579 (2011)
  59. Unactivated PKR exists in an open conformation capable of binding nucleotides. Lemaire PA, Tessmer I, Craig R, Erie DA, Cole JL. Biochemistry 45 9074-9084 (2006)
  60. Analysis of high-affinity binding of protein kinase R to double-stranded RNA. Husain B, Mukerji I, Cole JL. Biochemistry 51 8764-8770 (2012)
  61. Evaluating the therapeutic potential of ADAR1 inhibition for triple-negative breast cancer. Kung CP, Cottrell KA, Ryu S, Bramel ER, Kladney RD, Bao EA, Freeman EC, Sabloak T, Maggi L, Weber JD. Oncogene 40 189-202 (2021)
  62. Structural Basis for Noncanonical Substrate Recognition of Cofilin/ADF Proteins by LIM Kinases. Hamill S, Lou HJ, Turk BE, Boggon TJ. Mol Cell 62 397-408 (2016)
  63. A conserved Glu-Arg salt bridge connects coevolved motifs that define the eukaryotic protein kinase fold. Yang J, Wu J, Steichen JM, Kornev AP, Deal MS, Li S, Sankaran B, Woods VL, Taylor SS. J Mol Biol 415 666-679 (2012)
  64. Characterization of a ranavirus inhibitor of the antiviral protein kinase PKR. Rothenburg S, Chinchar VG, Dever TE. BMC Microbiol 11 56 (2011)
  65. Distal recognition sites in substrates are required for efficient phosphorylation by the cAMP-dependent protein kinase. Deminoff SJ, Ramachandran V, Herman PK. Genetics 182 529-539 (2009)
  66. Intrinsic RNA binding by the eukaryotic initiation factor 4F depends on a minimal RNA length but not on the m7G cap. Kaye NM, Emmett KJ, Merrick WC, Jankowsky E. J Biol Chem 284 17742-17750 (2009)
  67. Mapping of the auto-inhibitory interactions of protein kinase R by nuclear magnetic resonance. Gelev V, Aktas H, Marintchev A, Ito T, Frueh D, Hemond M, Rovnyak D, Debus M, Hyberts S, Usheva A, Halperin J, Wagner G. J Mol Biol 364 352-363 (2006)
  68. Protein kinase PKR mutants resistant to the poxvirus pseudosubstrate K3L protein. Seo EJ, Liu F, Kawagishi-Kobayashi M, Ung TL, Cao C, Dar AC, Sicheri F, Dever TE. Proc Natl Acad Sci U S A 105 16894-16899 (2008)
  69. Interaction between the tRNA-binding and C-terminal domains of Yeast Gcn2 regulates kinase activity in vivo. Lageix S, Zhang J, Rothenburg S, Hinnebusch AG. PLoS Genet 11 e1004991 (2015)
  70. The beta/Gcd7 subunit of eukaryotic translation initiation factor 2B (eIF2B), a guanine nucleotide exchange factor, is crucial for binding eIF2 in vivo. Dev K, Qiu H, Dong J, Zhang F, Barthlme D, Hinnebusch AG. Mol Cell Biol 30 5218-5233 (2010)
  71. Recognition of viral RNA stem-loops by the tandem double-stranded RNA binding domains of PKR. Dzananovic E, Patel TR, Deo S, McEleney K, Stetefeld J, McKenna SA. RNA 19 333-344 (2013)
  72. Control of serotonin transporter phosphorylation by conformational state. Zhang YW, Turk BE, Rudnick G. Proc Natl Acad Sci U S A 113 E2776-83 (2016)
  73. Crystal structure of the alpha subunit of human translation initiation factor 2B. Hiyama TB, Ito T, Imataka H, Yokoyama S. J Mol Biol 392 937-951 (2009)
  74. Sequence-based prediction of protein binding mode landscapes. Horvath A, Miskei M, Ambrus V, Vendruscolo M, Fuxreiter M. PLoS Comput Biol 16 e1007864 (2020)
  75. Erythropoietin signaling regulates heme biosynthesis. Chung J, Wittig JG, Ghamari A, Maeda M, Dailey TA, Bergonia H, Kafina MD, Coughlin EE, Minogue CE, Hebert AS, Li L, Kaplan J, Lodish HF, Bauer DE, Orkin SH, Cantor AB, Maeda T, Phillips JD, Coon JJ, Pagliarini DJ, Dailey HA, Paw BH. Elife 6 e24767 (2017)
  76. Real-time 2-5A kinetics suggest that interferons β and λ evade global arrest of translation by RNase L. Chitrakar A, Rath S, Donovan J, Demarest K, Li Y, Sridhar RR, Weiss SR, Kotenko SV, Wingreen NS, Korennykh A. Proc Natl Acad Sci U S A 116 2103-2111 (2019)
  77. A network of hydrophobic residues impeding helix alphaC rotation maintains latency of kinase Gcn2, which phosphorylates the alpha subunit of translation initiation factor 2. Gárriz A, Qiu H, Dey M, Seo EJ, Dever TE, Hinnebusch AG. Mol Cell Biol 29 1592-1607 (2009)
  78. The infectious bursal disease virus RNA-binding VP3 polypeptide inhibits PKR-mediated apoptosis. Busnadiego I, Maestre AM, Rodríguez D, Rodríguez JF. PLoS One 7 e46768 (2012)
  79. News eIF2alpha kinases provide a new solution to the puzzle of substrate specificity. Hinnebusch AG. Nat Struct Mol Biol 12 835-838 (2005)
  80. Heparin activates PKR by inducing dimerization. Anderson E, Pierre-Louis WS, Wong CJ, Lary JW, Cole JL. J Mol Biol 413 973-984 (2011)
  81. PKR inhibits the DNA damage response, and is associated with poor survival in AML and accelerated leukemia in NHD13 mice. Cheng X, Byrne M, Brown KD, Konopleva MY, Kornblau SM, Bennett RL, May WS. Blood 126 1585-1594 (2015)
  82. Structural analysis of adenovirus VAI RNA defines the mechanism of inhibition of PKR. Launer-Felty K, Wong CJ, Cole JL. Biophys J 108 748-757 (2015)
  83. dsRNA Binding Domain of PKR Is Proteolytically Released by Enterovirus A71 to Facilitate Viral Replication. Chang YH, Lau KS, Kuo RL, Horng JT. Front Cell Infect Microbiol 7 284 (2017)
  84. Native tertiary structure and nucleoside modifications suppress tRNA's intrinsic ability to activate the innate immune sensor PKR. Nallagatla SR, Jones CN, Ghosh SK, Sharma SD, Cameron CE, Spremulli LL, Bevilacqua PC. PLoS One 8 e57905 (2013)
  85. Structural effects of clinically observed mutations in JAK2 exons 13-15: comparison with V617F and exon 12 mutations. Lee TS, Ma W, Zhang X, Kantarjian H, Albitar M. BMC Struct Biol 9 58 (2009)
  86. Dynamic allostery-based molecular workings of kinase:peptide complexes. Ahuja LG, Aoto PC, Kornev AP, Veglia G, Taylor SS. Proc Natl Acad Sci U S A 116 15052-15061 (2019)
  87. Orthopoxvirus K3 orthologs show virus- and host-specific inhibition of the antiviral protein kinase PKR. Park C, Peng C, Rahman MJ, Haller SL, Tazi L, Brennan G, Rothenburg S. PLoS Pathog 17 e1009183 (2021)
  88. Phosphorylation of the alpha subunit of translation initiation factor-2 by PKR mediates protein synthesis inhibition in the mouse brain during status epilepticus. Carnevalli LS, Pereira CM, Jaqueta CB, Alves VS, Paiva VN, Vattem KM, Wek RC, Mello LE, Castilho BA. Biochem J 397 187-194 (2006)
  89. Requirement for kinase-induced conformational change in eukaryotic initiation factor 2alpha (eIF2alpha) restricts phosphorylation of Ser51. Dey M, Velyvis A, Li JJ, Chiu E, Chiovitti D, Kay LE, Sicheri F, Dever TE. Proc Natl Acad Sci U S A 108 4316-4321 (2011)
  90. Role for subgenomic mRNA in host translation inhibition during Sindbis virus infection of mammalian cells. Patel RK, Burnham AJ, Gebhart NN, Sokoloski KJ, Hardy RW. Virology 441 171-181 (2013)
  91. Structure of the Toxoplasma gondii ROP18 kinase domain reveals a second ligand binding pocket required for acute virulence. Lim D, Gold DA, Julien L, Rosowski EE, Niedelman W, Yaffe MB, Saeij JP. J Biol Chem 288 34968-34980 (2013)
  92. Analysis of PKR-RNA interactions by sedimentation velocity. Wong CJ, Launer-Felty K, Cole JL. Methods Enzymol 488 59-79 (2011)
  93. Dynamic flexibility of double-stranded RNA activated PKR in solution. Gabel F, Wang D, Madern D, Sadler A, Dayie K, Daryoush MZ, Schwahn D, Zaccai G, Lee X, Williams BR. J Mol Biol 359 610-623 (2006)
  94. Regulation of PKR by RNA: formation of active and inactive dimers. Husain B, Hesler S, Cole JL. Biochemistry 54 6663-6672 (2015)
  95. Structural and functional characterization of KEOPS dimerization by Pcc1 and its role in t6A biosynthesis. Wan LC, Pillon MC, Thevakumaran N, Sun Y, Chakrabartty A, Guarné A, Kurinov I, Durocher D, Sicheri F. Nucleic Acids Res 44 6971-6980 (2016)
  96. The caspase-generated fragments of PKR cooperate to activate full-length PKR and inhibit translation. Kalai M, Suin V, Festjens N, Meeus A, Bernis A, Wang XM, Saelens X, Vandenabeele P. Cell Death Differ 14 1050-1059 (2007)
  97. Diversity in viral anti-PKR mechanisms: a remarkable case of evolutionary convergence. Domingo-Gil E, Toribio R, Nájera JL, Esteban M, Ventoso I. PLoS One 6 e16711 (2011)
  98. Interaction of PKR with single-stranded RNA. Mayo CB, Cole JL. Sci Rep 7 3335 (2017)
  99. Structure of autoinhibited Akt1 reveals mechanism of PIP3-mediated activation. Truebestein L, Hornegger H, Anrather D, Hartl M, Fleming KD, Stariha JTB, Pardon E, Steyaert J, Burke JE, Leonard TA. Proc Natl Acad Sci U S A 118 e2101496118 (2021)
  100. A Single Amino Acid Dictates Protein Kinase R Susceptibility to Unrelated Viral Antagonists. Carpentier KS, Esparo NM, Child SJ, Geballe AP. PLoS Pathog 12 e1005966 (2016)
  101. Binding of eEF1A2 to the RNA-dependent protein kinase PKR modulates its activity and promotes tumour cell survival. Losada A, Muñoz-Alonso MJ, Martínez-Díez M, Gago F, Domínguez JM, Martínez-Leal JF, Galmarini CM. Br J Cancer 119 1410-1420 (2018)
  102. Blockade of the LRP16-PKR-NF-κB signaling axis sensitizes colorectal carcinoma cells to DNA-damaging cytotoxic therapy. Li X, Wu Z, An X, Mei Q, Bai M, Hanski L, Li X, Ahola T, Han W. Elife 6 e27301 (2017)
  103. Cloning, expression and functional analysis of PKR from grass carp (Ctenopharyngodon idellus). Hu YS, Li W, Li DM, Liu Y, Fan LH, Rao ZC, Lin G, Hu CY. Fish Shellfish Immunol 35 1874-1881 (2013)
  104. Enhanced interaction between pseudokinase and kinase domains in Gcn2 stimulates eIF2α phosphorylation in starved cells. Lageix S, Rothenburg S, Dever TE, Hinnebusch AG. PLoS Genet 10 e1004326 (2014)
  105. Magnesium-dependent interaction of PKR with adenovirus VAI. Launer-Felty K, Wong CJ, Wahid AM, Conn GL, Cole JL. J Mol Biol 402 638-644 (2010)
  106. Mechanistic characterization of the 5'-triphosphate-dependent activation of PKR: lack of 5'-end nucleobase specificity, evidence for a distinct triphosphate binding site, and a critical role for the dsRBD. Toroney R, Hull CM, Sokoloski JE, Bevilacqua PC. RNA 18 1862-1874 (2012)
  107. Structural basis of the substrate specificity of bifunctional isocitrate dehydrogenase kinase/phosphatase. Yates SP, Edwards TE, Bryan CM, Stein AJ, Van Voorhis WC, Myler PJ, Stewart LJ, Zheng J, Jia Z. Biochemistry 50 8103-8106 (2011)
  108. Translational signalling, atrogenic and myogenic gene expression during unloading and reloading of skeletal muscle in myostatin-deficient mice. Smith HK, Matthews KG, Oldham JM, Jeanplong F, Falconer SJ, Bass JJ, Senna-Salerno M, Bracegirdle JW, McMahon CD. PLoS One 9 e94356 (2014)
  109. Dusty protein kinases: primary structure, gene evolution, tissue specific expression and unique features of the catalytic domain. Peng J, Dong W, Chen Y, Mo R, Cheng JF, Hui CC, Mohandas N, Huang CH. Biochim Biophys Acta 1759 562-572 (2006)
  110. Mechanism of Protein Kinase R Inhibition by Human Cytomegalovirus pTRS1. Vincent HA, Ziehr B, Moorman NJ. J Virol 91 e01574-16 (2017)
  111. Substrate recognition of PLCγ1 via a specific docking surface on Itk. Xie Q, Joseph RE, Fulton DB, Andreotti AH. J Mol Biol 425 683-696 (2013)
  112. Activation of PKR by short stem-loop RNAs containing single-stranded arms. Mayo CB, Wong CJ, Lopez PE, Lary JW, Cole JL. RNA 22 1065-1075 (2016)
  113. Characterization of the NiRAN domain from RNA-dependent RNA polymerase provides insights into a potential therapeutic target against SARS-CoV-2. Dwivedy A, Mariadasse R, Ahmad M, Chakraborty S, Kar D, Tiwari S, Bhattacharyya S, Sonar S, Mani S, Tailor P, Majumdar T, Jeyakanthan J, Biswal BK. PLoS Comput Biol 17 e1009384 (2021)
  114. Parallel action of AtDRB2 and RdDM in the control of transposable element expression. Clavel M, Pélissier T, Descombin J, Jean V, Picart C, Charbonel C, Saez-Vásquez J, Bousquet-Antonelli C, Deragon JM. BMC Plant Biol 15 70 (2015)
  115. Species-specific inhibition of antiviral protein kinase R by capripoxviruses and vaccinia virus. Park C, Peng C, Brennan G, Rothenburg S. Ann N Y Acad Sci 1438 18-29 (2019)
  116. Structural Basis for Auto-Inhibition of the NDR1 Kinase Domain by an Atypically Long Activation Segment. Xiong S, Lorenzen K, Couzens AL, Templeton CM, Rajendran D, Mao DYL, Juang YC, Chiovitti D, Kurinov I, Guettler S, Gingras AC, Sicheri F. Structure 26 1101-1115.e6 (2018)
  117. The interferon-inducible protein TDRD7 inhibits AMP-activated protein kinase and thereby restricts autophagy-independent virus replication. Subramanian G, Popli S, Chakravarty S, Taylor RT, Chakravarti R, Chattopadhyay S. J Biol Chem 295 6811-6822 (2020)
  118. Domain interactions in adenovirus VAI RNA mediate high-affinity PKR binding. Launer-Felty K, Cole JL. J Mol Biol 426 1285-1295 (2014)
  119. Functional analysis of the short isoform of orf virus protein OV20.0. Tseng YY, Lin FY, Cheng SF, Tscharke D, Chulakasian S, Chou CC, Liu YF, Chang WS, Wong ML, Hsu WL. J Virol 89 4966-4979 (2015)
  120. Impact of the structural integrity of the three-way junction of adenovirus VAI RNA on PKR inhibition. Dzananovic E, Astha, Chojnowski G, Deo S, Booy EP, Padilla-Meier P, McEleney K, Bujnicki JM, Patel TR, McKenna SA. PLoS One 12 e0186849 (2017)
  121. RNA-dependent protein kinase PKR and the Z-DNA binding orthologue PKZ differ in their capacity to mediate initiation factor eIF2α-dependent inhibition of protein synthesis and virus-induced stress granule formation. Taghavi N, Samuel CE. Virology 443 48-58 (2013)
  122. Variola virus E3L Zα domain, but not its Z-DNA binding activity, is required for PKR inhibition. Thakur M, Seo EJ, Dever TE. RNA 20 214-227 (2014)
  123. Computational and Experimental Characterization of Patient Derived Mutations Reveal an Unusual Mode of Regulatory Spine Assembly and Drug Sensitivity in EGFR Kinase. Ruan Z, Katiyar S, Kannan N. Biochemistry 56 22-32 (2017)
  124. Analysis of PKR activation using analytical ultracentrifugation. Cole JL. Macromol Biosci 10 703-713 (2010)
  125. Differential regulation of PKD isoforms in oxidative stress conditions through phosphorylation of a conserved Tyr in the P+1 loop. Cobbaut M, Derua R, Döppler H, Lou HJ, Vandoninck S, Storz P, Turk BE, Seufferlein T, Waelkens E, Janssens V, Van Lint J. Sci Rep 7 887 (2017)
  126. Molecular evolution and functional divergence of eukaryotic translation initiation factor 2-alpha kinases. Krishna KH, Kumar MS. PLoS One 13 e0194335 (2018)
  127. A truncated Danio rerio PKZ isoform functionally interacts with eIF2α and inhibits protein synthesis. Liu ZY, Jia KT, Li C, Weng SP, Guo CJ, He JG. Gene 527 292-300 (2013)
  128. Ab initio modeling and experimental assessment of Janus Kinase 2 (JAK2) kinase-pseudokinase complex structure. Wan X, Ma Y, McClendon CL, Huang LJ, Huang N. PLoS Comput Biol 9 e1003022 (2013)
  129. Analysis of monomeric and dimeric phosphorylated forms of protein kinase R. Anderson E, Quartararo C, Brown RS, Shi Y, Yao X, Cole JL. Biochemistry 49 1217-1225 (2010)
  130. Signaling by the integrated stress response kinase PKR is fine-tuned by dynamic clustering. Zappa F, Muniozguren NL, Wilson MZ, Costello MS, Ponce-Rojas JC, Acosta-Alvear D. J Cell Biol 221 e202111100 (2022)
  131. Activation of the essential kinase PDK1 by phosphoinositide-driven trans-autophosphorylation. Levina A, Fleming KD, Burke JE, Leonard TA. Nat Commun 13 1874 (2022)
  132. Auto-phosphorylation Represses Protein Kinase R Activity. Wang D, de Weerd NA, Willard B, Polekhina G, Williams BR, Sadler AJ. Sci Rep 7 44340 (2017)
  133. The Regulatory and Kinase Domains but Not the Interdomain Linker Determine Human Double-stranded RNA-activated Kinase (PKR) Sensitivity to Inhibition by Viral Non-coding RNAs. Sunita S, Schwartz SL, Conn GL. J Biol Chem 290 28156-28165 (2015)
  134. The unfolded protein response controls endoplasmic reticulum stress-induced apoptosis of MCF-7 cells via a high dose of vitamin C treatment. Bober P, Tomková Z, Alexovič M, Ropovik I, Sabo J. Mol Biol Rep 46 1275-1284 (2019)
  135. "Unraveling the tail" of how SRPK1 phosphorylates ASF/SF2. Mao DY, Ceccarelli DF, Sicheri F. Mol Cell 29 535-537 (2008)
  136. A Gaussian network model study suggests that structural fluctuations are higher for inactive states than active states of protein kinases. Kalaivani R, Srinivasan N. Mol Biosyst 11 1079-1095 (2015)
  137. Depletion of eIF2·GTP·Met-tRNAi translation initiation complex up-regulates BRCA1 expression in vitro and in vivo. Aktas BH, Bordelois P, Peker S, Merajver S, Halperin JA. Oncotarget 6 6902-6914 (2015)
  138. Maladaptation after a virus host switch leads to increased activation of the pro-inflammatory NF-κB pathway. Yu H, Peng C, Zhang C, Stoian AMM, Tazi L, Brennan G, Rothenburg S. Proc Natl Acad Sci U S A 119 e2115354119 (2022)
  139. PKR stirs up inflammasomes. Stunden HJ, Latz E. Cell Res 23 168-170 (2013)
  140. The GCN2 inhibitor IMPACT contributes to diet-induced obesity and body temperature control. Pereira CM, Filev R, Dubiela FP, Brandão BB, Queiroz CM, Ludwig RG, Hipolide D, Longo BM, Mello LE, Mori MA, Castilho BA. PLoS One 14 e0217287 (2019)
  141. Phosphorylation of translation initiation factor eIF2α at Ser51 depends on site- and context-specific information. Uppala JK, Ghosh C, Sathe L, Dey M. FEBS Lett 592 3116-3125 (2018)
  142. Properties that rank protein:protein docking poses with high accuracy. Simões ICM, Coimbra JTS, Neves RPP, Costa IPD, Ramos MJ, Fernandes PA. Phys Chem Chem Phys 20 20927-20942 (2018)
  143. Unravelling the structural interactions between PKR kinase domain and its small molecule inhibitors using computational approaches. Barage S, Kulkarni A, Pal JK, Joshi M. J Mol Graph Model 75 322-329 (2017)
  144. Viral Evolved Inhibition Mechanism of the RNA Dependent Protein Kinase PKR's Kinase Domain, a Structural Perspective. Krishna KH, Vadlamudi Y, Kumar MS. PLoS One 11 e0153680 (2016)
  145. Design and synthesis of novel protein kinase R (PKR) inhibitors. Weintraub S, Yarnitzky T, Kahremany S, Barrera I, Viskind O, Rosenblum K, Niv MY, Gruzman A. Mol Divers 20 805-819 (2016)
  146. Double-Stranded RNA Dependent Kinase R Regulates Antibacterial Immunity in Sepsis. Yang Y, Xie L, Zhong Y, Zhong X, Meng R, Xue Q, Liang F, Zhao K, Tang Y. J Innate Immun 13 26-37 (2021)
  147. Inferring Methionine Sulfoxidation and serine Phosphorylation crosstalk from Phylogenetic analyses. Aledo JC. BMC Evol Biol 17 171 (2017)
  148. Long-range molecular dynamics show that inactive forms of Protein Kinase A are more dynamic than active forms. Kalaivani R, Narwani TJ, de Brevern AG, Srinivasan N. Protein Sci 28 543-560 (2019)
  149. Molecular dynamics reveal a novel kinase-substrate interface that regulates protein translation. Liu MS, Wang D, Morimoto H, Yim HC, Irving AT, Williams BR, Sadler AJ. J Mol Cell Biol 6 473-485 (2014)
  150. Role of the Interdomain Linker in RNA-Activated Protein Kinase Activation. Husain B, Mayo C, Cole JL. Biochemistry 55 253-261 (2016)
  151. News [It takes two RAFs to tango]. Lavoie H, Therrien M. Med Sci (Paris) 26 459-460 (2010)
  152. Lactococcus lactis Expressing Type I Interferon From Atlantic Salmon Enhances the Innate Antiviral Immune Response In Vivo and In Vitro. Muñoz C, González-Lorca J, Parra M, Soto S, Valdes N, Sandino AM, Vargas R, González A, Tello M. Front Immunol 12 696781 (2021)
  153. A measured approach: determining the PLCγ1 docking site on Itk using a biochemical ruler. Ghose R. J Mol Biol 425 679-682 (2013)
  154. Chemically reprogramming the phospho-transfer reaction to crosslink protein kinases to their substrates. Wong AW, Urisman A, Burlingame AL, Shokat KM. Protein Sci 28 654-662 (2019)
  155. Conservation of structural fluctuations in homologous protein kinases and its implications on functional sites. Kalaivani R, de Brevern AG, Srinivasan N. Proteins 84 957-978 (2016)
  156. Contribution of dsRBD2 to PKR Activation. Hesler S, Angeliadis M, Husain B, Cole JL. ACS Omega 6 11367-11374 (2021)
  157. Elucidation of molecular mechanism of stability of the heme-regulated eIF2α kinase upon binding of its ligand, hemin in its catalytic kinase domain. Bhavnani V, Kaviraj S, Panigrahi P, Suresh CG, Yapara S, Pal J. J Biomol Struct Dyn 36 2845-2861 (2018)
  158. HRI, a stress response eIF2α kinase, exhibits structural and functional stability at high temperature and alkaline conditions. Bhavnani V, Swarnendu K, Savergave L, Raghuwanshi AS, Kumar A, Kumar A, Pal J. Int J Biol Macromol 95 528-538 (2017)
  159. Introns encode dsRNAs undetected by RIG-I/MDA5/interferons and sensed via RNase L. Chitrakar A, Solorio-Kirpichyan K, Prangley E, Rath S, Du J, Korennykh A. Proc Natl Acad Sci U S A 118 e2102134118 (2021)
  160. PKD autoinhibition in trans regulates activation loop autophosphorylation in cis. Reinhardt R, Hirzel K, Link G, Eisler SA, Hägele T, Parson MAH, Burke JE, Hausser A, Leonard TA. Proc Natl Acad Sci U S A 120 e2212909120 (2023)
  161. A critical evaluation of protein kinase regulation by activation loop autophosphorylation. Reinhardt R, Leonard TA. Elife 12 e88210 (2023)
  162. Crocodilepox Virus Protein 157 Is an Independently Evolved Inhibitor of Protein Kinase R. Rahman MJ, Tazi L, Haller SL, Rothenburg S. Viruses 14 1564 (2022)
  163. HSV-1 Triggers an Antiviral Transcriptional Response during Viral Replication That Is Completely Abrogated in PKR-/- Cells. Pennisi R, Maria Teresa S. Pathogens 12 1126 (2023)
  164. Rescue of a Vaccinia Virus Mutant Lacking IFN Resistance Genes K1L and C7L by the Parapoxvirus Orf Virus. Riad S, Xiang Y, AlDaif B, Mercer AA, Fleming SB. Front Microbiol 11 1797 (2020)
  165. Temporal control of the integrated stress response by a stochastic molecular switch. Klein P, Kallenberger SM, Roth H, Roth K, Ly-Hartig TBN, Magg V, Aleš J, Talemi SR, Qiang Y, Wolf S, Oleksiuk O, Kurilov R, Di Ventura B, Bartenschlager R, Eils R, Rohr K, Hamprecht FA, Höfer T, Fackler OT, Stoecklin G, Ruggieri A. Sci Adv 8 eabk2022 (2022)


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