PKR

Summary

Gene Symbol: PKR
Description: eukaryotic translation initiation factor 2 alpha kinase 2
Alias: EIF2AK1, PKR, PPP1R83, PRKR, interferon-induced, double-stranded RNA-activated protein kinase, P1/eIF-2A protein kinase, double stranded RNA activated protein kinase, eIF-2A protein kinase 2, interferon-inducible elF2alpha kinase, p68 kinase, protein kinase R, protein kinase, interferon-inducible double stranded RNA dependent, protein phosphatase 1, regulatory subunit 83, tyrosine-protein kinase EIF2AK2
Species: human
Products:     PKR

Top Publications

  1. Bonnet M, Weil R, Dam E, Hovanessian A, Meurs E. PKR stimulates NF-kappaB irrespective of its kinase function by interacting with the IkappaB kinase complex. Mol Cell Biol. 2000;20:4532-42 pubmed
    The interferon (IFN)-induced double-stranded RNA-activated protein kinase PKR mediates inhibition of protein synthesis through phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2alpha) and is also involved in the ..
  2. Toth A, Devaux P, Cattaneo R, Samuel C. Protein kinase PKR mediates the apoptosis induction and growth restriction phenotypes of C protein-deficient measles virus. J Virol. 2009;83:961-8 pubmed publisher
    ..Here, we show that a major effector of the C phenotype is the RNA-dependent protein kinase PKR. Using human HeLa cells stably deficient in PKR as a result of RNA interference-mediated knockdown (PKR(kd) cells), ..
  3. Donze O, Abbas Terki T, Picard D. The Hsp90 chaperone complex is both a facilitator and a repressor of the dsRNA-dependent kinase PKR. EMBO J. 2001;20:3771-80 pubmed
    b>PKR, a member of the eukaryotic initiation-factor 2alpha (eIF-2alpha) kinase family, mediates the host antiviral response and is implicated in tumor suppression and apoptosis...
  4. Doria M, Neri F, Gallo A, Farace M, Michienzi A. Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection. Nucleic Acids Res. 2009;37:5848-58 pubmed publisher
    ..Overall these results suggest that HIV-1 has evolved mechanisms to take advantage of specific RNA editing activity of the host cell and disclose a stimulatory function of ADAR1 in the spread of HIV-1. ..
  5. Park I, Baek K, Cho E, Ahn B. PKR-dependent mechanisms of interferon-? for inhibiting hepatitis B virus replication. Mol Cells. 2011;32:167-72 pubmed publisher
    ..impaired in the cell in which the expression of IFN-inducible, double-stranded RNA-dependent protein kinase (PKR) was stably and specifically suppressed through RNA-interference...
  6. Roh M, Kwak J, Kim S, Lee H, Kwon H, Hwang T, et al. Expression of double-stranded RNA-activated protein kinase in small-size peripheral adenocarcinoma of the lung. Pathol Int. 2005;55:688-93 pubmed
    The authors investigated the protein expression of double-stranded RNA-activated protein kinase (PKR), which was identified by using a previous cDNA microarray study, to discover PKR's correlations with several pathological parameters ..
  7. Langland J, Kao P, Jacobs B. Nuclear factor-90 of activated T-cells: A double-stranded RNA-binding protein and substrate for the double-stranded RNA-dependent protein kinase, PKR. Biochemistry. 1999;38:6361-8 pubmed
    ..RNA-dependent manner likely by the interferon-induced, double-stranded RNA-dependent protein kinase, PKR. The NF90 protein was found to be expressed not only in T-cells, but also in nonimmune HeLa cells...
  8. Morimoto H, Okamura H, Yoshida K, Kitamura S, Haneji T. Okadaic acid induces apoptosis through double-stranded RNA-dependent protein kinase/eukaryotic initiation factor-2alpha pathway in human osteoblastic MG63 cells. J Biochem. 2004;136:433-8 pubmed
    Double-stranded RNA-dependent protein kinase (PKR) is a participant in the cellular antiviral response and phosphorylates the alpha-subunit of eukaryotic translation initiation factor 2alpha (eIF-2alpha) to block protein synthesis...
  9. Daher A, Longuet M, Dorin D, Bois F, Segeral E, Bannwarth S, et al. Two dimerization domains in the trans-activation response RNA-binding protein (TRBP) individually reverse the protein kinase R inhibition of HIV-1 long terminal repeat expression. J Biol Chem. 2001;276:33899-905 pubmed
    ..TRBP interacts with the interferon-induced protein kinase R (PKR) and inhibits its activity...

More Information

Publications90

  1. Chen G, Lai P, Ho R, Chan P, Xu H, Wong J, et al. Reduction of double-stranded RNA-activated protein kinase in hepatocellular carcinoma associated with hepatitis B virus. J Med Virol. 2004;73:187-94 pubmed
    ..Double-stranded RNA (dsRNA)-activated protein kinase (PKR) is an interferon-induced, serine/threonine protein kinase...
  2. McAllister C, Samuel C. The RNA-activated protein kinase enhances the induction of interferon-beta and apoptosis mediated by cytoplasmic RNA sensors. J Biol Chem. 2009;284:1644-51 pubmed publisher
    ..PRNAs 50 nucleotides long as well as polyinosinic-polycytidylic acid activated the RNA-dependent protein kinase (PKR) and induced significant levels of IFN-beta and apoptosis, whereas shorter PRNAs and chemically synthesized dsRNAs ..
  3. Mounir Z, Krishnamoorthy J, Robertson G, Scheuner D, Kaufman R, Georgescu M, et al. Tumor suppression by PTEN requires the activation of the PKR-eIF2alpha phosphorylation pathway. Sci Signal. 2009;2:ra85 pubmed publisher
    ..of eIF2alpha phosphorylation are cytoprotective, phosphorylation of eIF2alpha by RNA-dependent protein kinase (PKR) is largely proapoptotic and tumor suppressing...
  4. Toroney R, Nallagatla S, Boyer J, Cameron C, Bevilacqua P. Regulation of PKR by HCV IRES RNA: importance of domain II and NS5A. J Mol Biol. 2010;400:393-412 pubmed publisher
    b>Protein kinase R (PKR) is an essential component of the innate immune response...
  5. Gale M, Korth M, Tang N, Tan S, Hopkins D, Dever T, et al. Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein. Virology. 1997;230:217-27 pubmed
    ..in mediating HCV IFN resistance, we tested whether the NS5A protein could regulate the IFN-induced protein kinase, PKR, a mediator of IFN-induced antiviral resistance and a target of viral and cellular inhibitors...
  6. Peters G, Hartmann R, Qin J, Sen G. Modular structure of PACT: distinct domains for binding and activating PKR. Mol Cell Biol. 2001;21:1908-20 pubmed
    PACT is a 35-kDa human protein that can directly bind and activate the latent protein kinase, PKR. Here we report that PKR activation by PACT causes cellular apoptosis in addition to PKR autophosphorylation and translation inhibition...
  7. Cosentino G, Venkatesan S, Serluca F, Green S, Mathews M, 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;92:9445-9 pubmed
    ..blot analysis were used to demonstrate dimerization of human double-stranded RNA (dsRNA)-dependent protein kinase (PKR) in vivo and in vitro...
  8. McMillan N, Chun R, Siderovski D, Galabru J, Toone W, Samuel C, et al. HIV-1 Tat directly interacts with the interferon-induced, double-stranded RNA-dependent kinase, PKR. Virology. 1995;213:413-24 pubmed
    We present evidence that the HIV-1 Tat protein and the RNA-dependent cellular protein kinase, PKR, interact with each other both in vitro and in vivo...
  9. Zhang P, Samuel C. Protein kinase PKR plays a stimulus- and virus-dependent role in apoptotic death and virus multiplication in human cells. J Virol. 2007;81:8192-200 pubmed
    The protein kinase regulated by double-stranded RNA (dsRNA), PKR, is implicated in a range of biologic processes, including apoptotic death and interferon antiviral responses, based in part on studies with mouse cells genetically ..
  10. Lee E, Yoon C, Kim Y, Bae Y. The double-strand RNA-dependent protein kinase PKR plays a significant role in a sustained ER stress-induced apoptosis. FEBS Lett. 2007;581:4325-32 pubmed
    ..Here, we demonstrate that the double strand RNA-dependent protein kinase (PKR) is involved in the ER stress-mediated signaling pathway...
  11. Zhang F, Romano P, Nagamura Inoue T, Tian B, Dever T, Mathews M, et al. Binding of double-stranded RNA to protein kinase PKR is required for dimerization and promotes critical autophosphorylation events in the activation loop. J Biol Chem. 2001;276:24946-58 pubmed
    Protein kinase PKR is activated by double-stranded RNA (dsRNA) and phosphorylates translation initiation factor 2alpha to inhibit protein synthesis in virus-infected mammalian cells...
  12. Gil J, Garcia M, Gomez Puertas P, Guerra S, Rullas J, Nakano H, et al. TRAF family proteins link PKR with NF-kappa B activation. Mol Cell Biol. 2004;24:4502-12 pubmed
    The double-stranded RNA (dsRNA)-dependent protein kinase PKR activates NF-kappa B via the I kappa B kinase (IKK) complex, but little is known about additional molecules that may be involved in this pathway...
  13. Singh M, Patel R. Increased interaction between PACT molecules in response to stress signals is required for PKR activation. J Cell Biochem. 2012;113:2754-64 pubmed publisher
    b>PKR (protein kinase, RNA activated) is an interferon (IFN)-induced serine-threonine protein kinase and is one of the key mediators in IFN's cellular actions...
  14. Pavio N, Taylor D, Lai M. Detection of a novel unglycosylated form of hepatitis C virus E2 envelope protein that is located in the cytosol and interacts with PKR. J Virol. 2002;76:1265-72 pubmed
    ..Alpha interferon (IFN-alpha) treatment or overexpression of the double-stranded RNA-activated protein kinase (PKR) significantly increased the stability of E2-p38, consistent with a previous report (D. R. Taylor, S. T. Shi, P. R...
  15. Pang Q, Christianson T, Koretsky T, Carlson H, David L, Keeble W, et al. Nucleophosmin interacts with and inhibits the catalytic function of eukaryotic initiation factor 2 kinase PKR. J Biol Chem. 2003;278:41709-17 pubmed
    In normal cells the protein kinase PKR effects apoptosis in response to various extra and intracellular cues and can also function to suppress the neoplastic phenotype...
  16. Polyak S, Tang N, Wambach M, Barber G, Katze M. The P58 cellular inhibitor complexes with the interferon-induced, double-stranded RNA-dependent protein kinase, PKR, to regulate its autophosphorylation and activity. J Biol Chem. 1996;271:1702-7 pubmed
    ..to as P58, is a cellular inhibitor of the interferon-induced, double-stranded RNA-activated protein kinase, PKR. The P58 protein inhibits both the autophosphorylation of PKR and the phosphorylation of the PKR natural substrate, ..
  17. Gilfoy F, Mason P. West Nile virus-induced interferon production is mediated by the double-stranded RNA-dependent protein kinase PKR. J Virol. 2007;81:11148-58 pubmed
    ..Here we demonstrate that the double-stranded RNA (dsRNA)-dependent protein kinase PKR, which has been shown to function as a PRR in cells treated with the dsRNA mimetic poly(I:C), serves as a PRR in ..
  18. Williams B. PKR; a sentinel kinase for cellular stress. Oncogene. 1999;18:6112-20 pubmed
    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...
  19. Parker L, Fierro Monti I, Mathews M. Nuclear factor 90 is a substrate and regulator of the eukaryotic initiation factor 2 kinase double-stranded RNA-activated protein kinase. J Biol Chem. 2001;276:32522-30 pubmed
    ..motifs (dsRBMs) and interacts with highly structured RNAs as well as the dsRNA-activated protein kinase, PKR. In this report, we characterize the biochemical interactions between these two dsRBM containing proteins...
  20. Gil J, Alcami J, Esteban M. Activation of NF-kappa B by the dsRNA-dependent protein kinase, PKR involves the I kappa B kinase complex. Oncogene. 2000;19:1369-78 pubmed
    Besides its known role as a translational controlling factor, the double stranded RNA-dependent protein kinase (PKR) is a key transcriptional regulator exerting antiviral and antitumoural activities...
  21. Deb A, Zamanian Daryoush M, Xu Z, Kadereit S, Williams B. Protein kinase PKR is required for platelet-derived growth factor signaling of c-fos gene expression via Erks and Stat3. EMBO J. 2001;20:2487-96 pubmed
    The double-stranded RNA (dsRNA)-activated protein kinase PKR is an interferon (IFN)-induced enzyme that controls protein synthesis through phosphorylation of eukaryotic initiation factor 2alpha (eIF-2alpha)...
  22. Taghavi N, Samuel C. Protein kinase PKR catalytic activity is required for the PKR-dependent activation of mitogen-activated protein kinases and amplification of interferon beta induction following virus infection. Virology. 2012;427:208-16 pubmed publisher
    The protein kinase regulated by RNA (PKR) enhances both activation of mitogen-activated protein kinases and the induction of interferon beta (IFN-?) by measles virus defective in C-protein expression (C(ko))...
  23. Arnaud N, Dabo S, Akazawa D, Fukasawa M, Shinkai Ouchi F, Hugon J, et al. Hepatitis C virus reveals a novel early control in acute immune response. PLoS Pathog. 2011;7:e1002289 pubmed publisher
    ..by cleaving MAVS through its NS3/4A protease and by controlling cellular translation through activation of PKR, an eIF2?-kinase containing dsRNA-binding domains (DRBD)...
  24. Clerzius G, Gélinas J, Daher A, Bonnet M, Meurs E, Gatignol A. ADAR1 interacts with PKR during human immunodeficiency virus infection of lymphocytes and contributes to viral replication. J Virol. 2009;83:10119-28 pubmed publisher
    The interferon-induced protein kinase RNA activated (PKR) is activated after virus infection...
  25. Pavio N, Romano P, Graczyk T, Feinstone S, Taylor D. Protein synthesis and endoplasmic reticulum stress can be modulated by the hepatitis C virus envelope protein E2 through the eukaryotic initiation factor 2alpha kinase PERK. J Virol. 2003;77:3578-85 pubmed
    ..protein that contains a region of sequence homology with the double-stranded RNA-activated protein kinase PKR and its substrate, the eukaryotic translation initiation factor 2 (eIF2)...
  26. Takizawa T, Tatematsu C, Nakanishi Y. Double-stranded RNA-activated protein kinase interacts with apoptosis signal-regulating kinase 1. Implications for apoptosis signaling pathways. Eur J Biochem. 2002;269:6126-32 pubmed
    Double-stranded RNA-activated protein kinase (PKR), a serine/threonine kinase, is activated in virus-infected cells and acts as an antiviral machinery of type I interferons...
  27. Huang X, Hutchins B, Patel R. The C-terminal, third conserved motif of the protein activator PACT plays an essential role in the activation of double-stranded-RNA-dependent protein kinase (PKR). Biochem J. 2002;366:175-86 pubmed
    ..of the antiviral and antiproliferative actions of interferon is double-stranded-RNA-dependent protein kinase (PKR). PKR activity is also involved in the regulation of cell proliferation, apoptosis and signal transduction...
  28. Garaigorta U, Chisari F. Hepatitis C virus blocks interferon effector function by inducing protein kinase R phosphorylation. Cell Host Microbe. 2009;6:513-22 pubmed publisher
    ..We now show that HCV infection triggers phosphorylation and activation of the RNA-dependent protein kinase PKR, which inhibits eukaryotic translation initiation factor eIF2 alpha and attenuates ISG protein expression despite ..
  29. Bose A, Mouton Liger F, Paquet C, Mazot P, Vigny M, Gray F, et al. Modulation of tau phosphorylation by the kinase PKR: implications in Alzheimer's disease. Brain Pathol. 2011;21:189-200 pubmed publisher
    Double-stranded RNA dependent kinase (PKR) is a pro-apoptotic kinase that controls protein translation. Previous studies revealed that activated PKR is increased in brains with Alzheimer's disease (AD)...
  30. Bennett R, Blalock W, Abtahi D, Pan Y, Moyer S, May W. RAX, the PKR activator, sensitizes cells to inflammatory cytokines, serum withdrawal, chemotherapy, and viral infection. Blood. 2006;108:821-9 pubmed
    While the interferon (IFN)-inducible double-stranded RNA (dsRNA)-dependent protein kinase PKR is reported to initiate apoptosis in some instances, the mechanism by which diverse stress stimuli activate PKR remains unknown...
  31. Arnaud N, Dabo S, Maillard P, Budkowska A, Kalliampakou K, Mavromara P, et al. Hepatitis C virus controls interferon production through PKR activation. PLoS ONE. 2010;5:e10575 pubmed publisher
    ..The cellular protein kinase PKR is an important regulator of translation, through the phosphorylation of its substrate the eIF2alpha initiation ..
  32. McAllister C, Taghavi N, Samuel C. Protein kinase PKR amplification of interferon ? induction occurs through initiation factor eIF-2?-mediated translational control. J Biol Chem. 2012;287:36384-92 pubmed publisher
    The protein kinase PKR is activated by RNA with double-stranded (ds) structure and subsequently impairs translation through phosphorylation of protein synthesis initiation factor eIF-2?...
  33. Zamanian Daryoush M, Mogensen T, DiDonato J, Williams B. NF-kappaB activation by double-stranded-RNA-activated protein kinase (PKR) is mediated through NF-kappaB-inducing kinase and IkappaB kinase. Mol Cell Biol. 2000;20:1278-90 pubmed
    The interferon (IFN)-inducible double-stranded-RNA (dsRNA)-activated serine-threonine protein kinase (PKR) is a major mediator of the antiviral and antiproliferative activities of IFNs...
  34. Wang Y, Samuel C. Adenosine deaminase ADAR1 increases gene expression at the translational level by decreasing protein kinase PKR-dependent eIF-2alpha phosphorylation. J Mol Biol. 2009;393:777-87 pubmed publisher
    ..The activation of PKR (protein kinase regulated by RNA) protein kinase and the phosphorylation of translation initiation factor eIF-..
  35. Pereira R, Teixeira K, Barreto de Souza V, Calegari Silva T, De Melo L, Soares D, et al. Novel role for the double-stranded RNA-activated protein kinase PKR: modulation of macrophage infection by the protozoan parasite Leishmania. FASEB J. 2010;24:617-26 pubmed publisher
    ..Double-stranded RNA (dsRNA)-activated protein kinase R (PKR), a classic antiviral protein, is able to regulate a number of signaling pathways and macrophage ..
  36. Pataer A, Raso M, Correa A, Behrens C, Tsuta K, Solis L, et al. Prognostic significance of RNA-dependent protein kinase on non-small cell lung cancer patients. Clin Cancer Res. 2010;16:5522-8 pubmed publisher
    The role of RNA-dependent protein kinase (PKR) in antiviral defense mechanisms and in cellular differentiation, growth, and apoptosis is well known, but the role of PKR in human lung cancer remains poorly understood...
  37. Singh M, Castillo D, Patel C, Patel R. Stress-induced phosphorylation of PACT reduces its interaction with TRBP and leads to PKR activation. Biochemistry. 2011;50:4550-60 pubmed publisher
    PACT is a stress-modulated activator of interferon (IFN)-induced double-stranded (ds) RNA-activated protein kinase (PKR) and is an important regulator of PKR-dependent signaling pathways...
  38. McAllister C, Toth A, Zhang P, Devaux P, Cattaneo R, Samuel C. Mechanisms of protein kinase PKR-mediated amplification of beta interferon induction by C protein-deficient measles virus. J Virol. 2010;84:380-6 pubmed publisher
    ..Furthermore, protein kinase PKR and mitochondrial adapter IPS-1 were required for maximal C(ko)-mediated IFN-beta induction, which correlated with ..
  39. Rahman M, Liu J, Chan W, Rothenburg S, McFadden G. Myxoma virus protein M029 is a dual function immunomodulator that inhibits PKR and also conscripts RHA/DHX9 to promote expanded host tropism and viral replication. PLoS Pathog. 2013;9:e1003465 pubmed publisher
    ..Using proteomic approaches, we have identified Protein Kinase R (PKR) and RNA helicase A (RHA)/DHX9 as two cellular binding partners of M029 protein...
  40. Meurs E, Chong K, Galabru J, Thomas N, Kerr I, Williams B, et al. Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon. Cell. 1990;62:379-90 pubmed
    The double-stranded (ds) RNA-activated protein kinase from human cells is a 68 kd protein (p68 kinase) induced by interferon...
  41. Garcia M, Collado M, Munoz Fontela C, Matheu A, Marcos Villar L, Arroyo J, et al. Antiviral action of the tumor suppressor ARF. EMBO J. 2006;25:4284-92 pubmed
    ..against viral infection in a gene dosage-dependent manner, and that this antiviral action is mediated in part by PKR through a mechanism that involves ARF-induced release of PKR from nucleophosmin complexes...
  42. Nanduri S, Carpick B, Yang Y, Williams B, Qin J. Structure of the double-stranded RNA-binding domain of the protein kinase PKR reveals the molecular basis of its dsRNA-mediated activation. EMBO J. 1998;17:5458-65 pubmed
    Protein kinase PKR is an interferon-induced enzyme that plays a key role in the control of viral infections and cellular homeostasis...
  43. Romano P, Garcia Barrio M, Zhang X, Wang Q, Taylor D, Zhang F, et al. Autophosphorylation in the activation loop is required for full kinase activity in vivo of human and yeast eukaryotic initiation factor 2alpha kinases PKR and GCN2. Mol Cell Biol. 1998;18:2282-97 pubmed
    The human double-stranded RNA-dependent protein kinase (PKR) is an important component of the interferon response to virus infection...
  44. Brand S, Kobayashi R, Mathews M. The Tat protein of human immunodeficiency virus type 1 is a substrate and inhibitor of the interferon-induced, virally activated protein kinase, PKR. J Biol Chem. 1997;272:8388-95 pubmed
    We demonstrate that the interferon-induced, double-stranded (ds) RNA-activated kinase, PKR, is able to bind to and phosphorylate the human immunodeficiency virus type 1 (HIV-1) trans-activating protein, Tat...
  45. Taylor D, Lee S, Romano P, Marshak D, Hinnebusch A, Esteban M, et al. Autophosphorylation sites participate in the activation of the double-stranded-RNA-activated protein kinase PKR. Mol Cell Biol. 1996;16:6295-302 pubmed
    The interferon-induced RNA-dependent protein kinase PKR is found in cells in a latent state. In response to the binding of double-stranded RNA, the enzyme becomes activated and autophosphorylated on several serine and threonine residues...
  46. Endo Munoz L, Warby T, Harrich D, McMillan N. Phosphorylation of HIV Tat by PKR increases interaction with TAR RNA and enhances transcription. Virol J. 2005;2:17 pubmed
    The interferon (IFN)-induced, dsRNA-dependent serine/threonine protein kinase, PKR, plays a key regulatory role in the IFN-mediated anti-viral response by blocking translation in the infected cell by phosphorylating the alpha subunit of ..
  47. Mouton Liger F, Paquet C, Dumurgier J, Bouras C, Pradier L, Gray F, et al. Oxidative stress increases BACE1 protein levels through activation of the PKR-eIF2? pathway. Biochim Biophys Acta. 2012;1822:885-96 pubmed publisher
    ..b>PKR (double-stranded RNA dependant protein kinase) is a pro-apoptotic kinase that phosphorylates eIF2? and modulates ..
  48. Tu Y, Yu C, Liang J, Lin E, Liao C, Lin Y. Blocking double-stranded RNA-activated protein kinase PKR by Japanese encephalitis virus nonstructural protein 2A. J Virol. 2012;86:10347-58 pubmed publisher
    ..The interferon (IFN)-induced double-stranded RNA (dsRNA)-activated protein kinase (PKR) phosphorylates the eukaryotic translation initiation factor 2? subunit (eIF2?) after sensing viral RNA and results ..
  49. Silva A, Whitmore M, Xu Z, Jiang Z, Li X, Williams B. Protein kinase R (PKR) interacts with and activates mitogen-activated protein kinase kinase 6 (MKK6) in response to double-stranded RNA stimulation. J Biol Chem. 2004;279:37670-6 pubmed
    The double-stranded RNA (dsRNA)-activated protein kinase R (PKR) has been invoked in different signaling pathways...
  50. Clerzius G, Gélinas J, Gatignol A. Multiple levels of PKR inhibition during HIV-1 replication. Rev Med Virol. 2011;21:42-53 pubmed publisher
    ..a better understanding of the weak efficacy of the IFN-stimulated genes, such as the protein kinase RNA-activated (PKR), which results in viral progression...
  51. Meusel T, Kehoe K, Imani F. Protein kinase R regulates double-stranded RNA induction of TNF-alpha but not IL-1 beta mRNA in human epithelial cells. J Immunol. 2002;168:6429-35 pubmed
    ..Our data show that dsRNA activation of dsRNA-activated protein kinase (PKR) is associated with induction of TNF-alpha but not IL-1 beta expression...
  52. Toth A, Li Z, Cattaneo R, Samuel C. RNA-specific adenosine deaminase ADAR1 suppresses measles virus-induced apoptosis and activation of protein kinase PKR. J Biol Chem. 2009;284:29350-6 pubmed publisher
    ..in ADAR1(kd) cells following infection with wild type and V(ko) virus correlated with enhanced activation of PKR kinase and interferon regulatory factor IRF-3...
  53. Hiasa Y, Kamegaya Y, Nuriya H, Onji M, Kohara M, Schmidt E, et al. Protein kinase R is increased and is functional in hepatitis C virus-related hepatocellular carcinoma. Am J Gastroenterol. 2003;98:2528-34 pubmed
    b>Protein kinase R (PKR) interacts with dsRNA and phosphorylates eukaryotic initiation factor-2 (eIF2alpha), which in turn inhibits host translation initiation as well as hepatitis C virus (HCV) translation...
  54. Mouton Liger F, Paquet C, Dumurgier J, Lapalus P, Gray F, Laplanche J, et al. Increased cerebrospinal fluid levels of double-stranded RNA-dependant protein kinase in Alzheimer's disease. Biol Psychiatry. 2012;71:829-35 pubmed publisher
    ..The proapoptotic kinase R (PKR), is activated by A? accumulates in degenerating neurons in AD brains and controls protein synthesis and indirectly ..
  55. McCormack S, Thomis D, Samuel C. 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;188:47-56 pubmed
  56. Patel R, Handy I, Patel C. Contribution of double-stranded RNA-activated protein kinase toward antiproliferative actions of heparin on vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2002;22:1439-44 pubmed
    ..action of heparin is in part mediated by its ability to activate double-stranded RNA-activated protein kinase (PKR), an interferon-induced protein kinase...
  57. Kim S, Gunnery S, Choe J, Mathews M. Neoplastic progression in melanoma and colon cancer is associated with increased expression and activity of the interferon-inducible protein kinase, PKR. Oncogene. 2002;21:8741-8 pubmed
    The interferon-inducible, double-stranded RNA (dsRNA)-activated protein kinase, PKR, plays key roles in regulation of cell growth and differentiation, and has been postulated as a tumor suppressor...
  58. Yang X, Chan C. Repression of PKR mediates palmitate-induced apoptosis in HepG2 cells through regulation of Bcl-2. Cell Res. 2009;19:469-86 pubmed publisher
    The present study shows that double-stranded RNA-dependent protein kinase (PKR) regulates the protein expression level and phosphorylation of Bcl-2 and plays an anti-apoptotic role in human hepatocellular carcinoma cells (HepG2)...
  59. Alisi A, Mele R, Spaziani A, Tavolaro S, Palescandolo E, Balsano C. Thr 446 phosphorylation of PKR by HCV core protein deregulates G2/M phase in HCC cells. J Cell Physiol. 2005;205:25-31 pubmed
    ..Different pathways mediate G2/M arrest: such as p53 and double strand RNA protein kinase (PKR)...
  60. Zhang P, Jacobs B, Samuel C. Loss of protein kinase PKR expression in human HeLa cells complements the vaccinia virus E3L deletion mutant phenotype by restoration of viral protein synthesis. J Virol. 2008;82:840-8 pubmed
    ..Among the cellular proteins implicated as targets of E3L is the protein kinase regulated by RNA (PKR)...
  61. Mittelstadt M, Frump A, Khuu T, Fowlkes V, Handy I, Patel C, et al. Interaction of human tRNA-dihydrouridine synthase-2 with interferon-induced protein kinase PKR. Nucleic Acids Res. 2008;36:998-1008 pubmed
    b>PKR is an interferon (IFN)-induced protein kinase, which is involved in regulation of antiviral innate immunity, stress signaling, cell proliferation and programmed cell death...
  62. Zhang P, Samuel C. Induction of protein kinase PKR-dependent activation of interferon regulatory factor 3 by vaccinia virus occurs through adapter IPS-1 signaling. J Biol Chem. 2008;283:34580-7 pubmed publisher
    ..To test in human cells the role of the protein kinase regulated by RNA (PKR) in IRF-3 activation, HeLa cells made stably deficient in PKR using an RNA interference strategy were compared with ..
  63. Ito M, Onuki R, Bando Y, Tohyama M, Sugiyama Y. Phosphorylated PKR contributes the induction of GRP94 under ER stress. Biochem Biophys Res Commun. 2007;360:615-20 pubmed
    Phosphorylated double-stranded RNA-dependent protein kinase (PKR) is thought to play an important role during ER stress induced cell death, but its molecular mechanism of action has not yet been clarified completely...
  64. Xu Z, Williams B. The B56alpha regulatory subunit of protein phosphatase 2A is a target for regulation by double-stranded RNA-dependent protein kinase PKR. Mol Cell Biol. 2000;20:5285-99 pubmed
    b>PKR is a cellular serine/threonine kinase that phosphorylates eukaryotic translation initiation factor 2alpha (eIF2alpha) to regulate protein synthesis...
  65. Kang J, Kwon S, Park S, Kim Y, Choi S, Kim J, et al. PKR protein kinase is activated by hepatitis C virus and inhibits viral replication through translational control. Virus Res. 2009;142:51-6 pubmed publisher
    ..here that HCV JFH1 infection of human hepatoma Huh-7 cells leads to the activation of IFN-inducible protein kinase PKR and phosphorylation of the translation initiation factor eIF2alpha...
  66. Saelens X, Kalai M, Vandenabeele P. Translation inhibition in apoptosis: caspase-dependent PKR activation and eIF2-alpha phosphorylation. J Biol Chem. 2001;276:41620-8 pubmed
    The protein kinase PKR is a major player in the cellular antiviral response, acting mainly by phosphorylation of the alpha-subunit of the eukaryotic translation initiation factor 2 (eIF2-alpha) to block de novo protein synthesis...
  67. Cuddihy A, Wong A, Tam N, Li S, Koromilas A. The double-stranded RNA activated protein kinase PKR physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro. Oncogene. 1999;18:2690-702 pubmed
    ..The double-stranded RNA activated protein kinase PKR is a serine/threonine kinase that modulates protein synthesis through the phosphorylation of translation initiation ..
  68. Hii S, Hardy L, Crough T, Payne E, Grimmett K, Gill D, et al. Loss of PKR activity in chronic lymphocytic leukemia. Int J Cancer. 2004;109:329-35 pubmed
    There are a number of observations that suggest the dsRNA-activated protein kinase, PKR, may play an active role in formation and maintenance of leukemia, including nonrandom chromosomal deletions in acute leukemia as well as truncations ..
  69. Takeuchi K, Komatsu T, Kitagawa Y, Sada K, Gotoh B. Sendai virus C protein plays a role in restricting PKR activation by limiting the generation of intracellular double-stranded RNA. J Virol. 2008;82:10102-10 pubmed publisher
    ..caused phosphorylation of both the translation initiation factor eIF2alpha and dsRNA-dependent protein kinase (PKR)...
  70. Wang X, Liao Y, Yap P, Png K, Tam J, Liu D. Inhibition of protein kinase R activation and upregulation of GADD34 expression play a synergistic role in facilitating coronavirus replication by maintaining de novo protein synthesis in virus-infected cells. J Virol. 2009;83:12462-72 pubmed publisher
    ..To understand whether this suppression is through inhibition of protein kinase R (PKR), the double-stranded-RNA-dependent kinase that is one of the main kinases responsible for ..
  71. Taylor D, Shi S, Romano P, Barber G, Lai M. Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science. 1999;285:107-10 pubmed
    ..protein E2 contains a sequence identical with phosphorylation sites of the interferon-inducible protein kinase PKR and the translation initiation factor eIF2alpha, a target of PKR...
  72. Roy S, Katze M, Parkin N, Edery I, Hovanessian A, Sonenberg N. Control of the interferon-induced 68-kilodalton protein kinase by the HIV-1 tat gene product. Science. 1990;247:1216-9 pubmed
    ..effect on translation in vitro by activating the interferon-induced 68-kilodalton protein kinase (p68 kinase)...
  73. Sharma K, Tripathi S, Ranjan P, Kumar P, Garten R, Deyde V, et al. Influenza A virus nucleoprotein exploits Hsp40 to inhibit PKR activation. PLoS ONE. 2011;6:e20215 pubmed publisher
    Double-stranded RNA dependent protein kinase (PKR) is a key regulator of the anti-viral innate immune response in mammalian cells...
  74. Patel R, Sen G. PACT, a protein activator of the interferon-induced protein kinase, PKR. EMBO J. 1998;17:4379-90 pubmed
    b>PKR, a latent protein kinase, mediates the antiviral actions of interferon. It is also involved in cellular signal transduction, apoptosis, growth regulation and differentiation...
  75. Sadler A, Latchoumanin O, Hawkes D, Mak J, Williams B. An antiviral response directed by PKR phosphorylation of the RNA helicase A. PLoS Pathog. 2009;5:e1000311 pubmed publisher
    The double-stranded RNA-activated protein kinase R (PKR) is a key regulator of the innate immune response...
  76. Onuki R, Bando Y, Suyama E, Katayama T, Kawasaki H, Baba T, et al. An RNA-dependent protein kinase is involved in tunicamycin-induced apoptosis and Alzheimer's disease. EMBO J. 2004;23:959-68 pubmed
    ..We identified a double-stranded RNA-dependent protein kinase (PKR) as one of the participants in this process...
  77. Nallagatla S, Hwang J, Toroney R, Zheng X, Cameron C, Bevilacqua P. 5'-triphosphate-dependent activation of PKR by RNAs with short stem-loops. Science. 2007;318:1455-8 pubmed
    ..immune system, and a component of this response is the interferon-induced enzyme RNA-activated protein kinase (PKR). The major activators of PKR have been proposed to be long double-stranded RNAs...
  78. Clerzius G, Shaw E, Daher A, Burugu S, Gélinas J, Ear T, et al. The PKR activator, PACT, becomes a PKR inhibitor during HIV-1 replication. Retrovirology. 2013;10:96 pubmed publisher
    HIV-1 translation is modulated by the activation of the interferon (IFN)-inducible Protein Kinase RNA-activated (PKR)...
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    The TAR RNA binding Protein, TRBP, inhibits the activity of the interferon-induced protein kinase R (PKR), whereas the PKR activator, PACT, activates its function...
  80. Cai R, Carpick B, Chun R, Jeang K, Williams B. HIV-I TAT inhibits PKR activity by both RNA-dependent and RNA-independent mechanisms. Arch Biochem Biophys. 2000;373:361-7 pubmed
    ..type 1 (HIV-1) is inhibited by interferons (IFNs), in part through activity of the IFN-inducible protein kinase PKR. To escape this antiviral effect, HIV-1 has developed strategies for blocking PKR function...
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    The IFN-induced double-stranded RNA-dependent protein kinase (PKR) is one of the four mammalian serine-threonine kinases (the three others being HRI, GCN2 and PERK) that phosphorylate the eIF2 alpha translation initiation factor, in ..