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

Top Publications

  1. pmc PKR stimulates NF-kappaB irrespective of its kinase function by interacting with the IkappaB kinase complex
    M C Bonnet
    Unité de Virologie et d Immunologie Cellulaire, URA CNRS 1930, Institut Pasteur, 75724 Paris Cedex 15, France
    Mol Cell Biol 20:4532-42. 2000
  2. pmc Systematic deletion of the adenovirus-associated RNAI terminal stem reveals a surprisingly active RNA inhibitor of double-stranded RNA-activated protein kinase
    Ahmed M Wahid
    Manchester Interdisciplinary Biocentre, Faculty of Life Sciences, University of Manchester, Manchester M1 7DN, United Kingdom
    J Biol Chem 283:17485-93. 2008
  3. pmc Double-stranded RNA-dependent protein kinase activation modulates endotoxin-induced diaphragm weakness
    G S Supinski
    Division of Pulmonary, Critical Care and Sleep Medicine, University of Kentucky, Lexington, Kentucky, USA
    J Appl Physiol (1985) 110:199-205. 2011
  4. pmc Hepatitis C virus controls interferon production through PKR activation
    Noëlla Arnaud
    Institut Pasteur, Unité Hépacivirus et Immunité Innée, Paris, France
    PLoS ONE 5:e10575. 2010
  5. pmc TRBP control of PACT-induced phosphorylation of protein kinase R is reversed by stress
    Aïcha Daher
    Virus Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Montreal, Quebec, Canada
    Mol Cell Biol 29:254-65. 2009
  6. pmc TRAF family proteins link PKR with NF-kappa B activation
    Jesus Gil
    Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Campus Universidad Autonoma, 28049 Madrid, Spain
    Mol Cell Biol 24:4502-12. 2004
  7. pmc Protein kinase PKR amplification of interferon β induction occurs through initiation factor eIF-2α-mediated translational control
    Christopher S McAllister
    Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California 93106, USA
    J Biol Chem 287:36384-92. 2012
  8. ncbi The Tat protein of human immunodeficiency virus type 1 is a substrate and inhibitor of the interferon-induced, virally activated protein kinase, PKR
    S R Brand
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11742, USA
    J Biol Chem 272:8388-95. 1997
  9. pmc The B56alpha regulatory subunit of protein phosphatase 2A is a target for regulation by double-stranded RNA-dependent protein kinase PKR
    Z Xu
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Mol Cell Biol 20:5285-99. 2000
  10. ncbi Binding of double-stranded RNA to protein kinase PKR is required for dimerization and promotes critical autophosphorylation events in the activation loop
    F Zhang
    Laboratory of Gene Regulation and Development, NICHHD, National Institutes of Health, Bethesda, MD 20892, USA
    J Biol Chem 276:24946-58. 2001

Research Grants

  1. Suppression of the Interferon Response by the Hepatitis C Virus
    FRANCIS VINCENT CHISARI; Fiscal Year: 2010
  2. TRANSLATIONAL CONTROL IN REGULATION OF APOPTOSIS
    Randal Kaufman; Fiscal Year: 2002
  3. The Role of PKR in a Novel IL-3 Signal Transduction Pathway
    William Stratford May; Fiscal Year: 2012
  4. Cigarette Smoke, RIG-like Helicases and Alveolar Remodeling
    Jack A Elias; Fiscal Year: 2012
  5. Charles E Samuel; Fiscal Year: 2014
  6. Molecular Insights into Activation and Substrate Recognition of Protein Kinase R
    Madhusudan Dey; Fiscal Year: 2012
  7. Tracy G Anthony; Fiscal Year: 2015
  8. James L Cole; Fiscal Year: 2016
  9. Trichothecene Toxicity and the Ribotoxic Stress Response
    James J Pestka; Fiscal Year: 2012
  10. YPE PETER DE JONG; Fiscal Year: 2015

Detail Information

Publications209 found, 100 shown here

  1. pmc PKR stimulates NF-kappaB irrespective of its kinase function by interacting with the IkappaB kinase complex
    M C Bonnet
    Unité de Virologie et d Immunologie Cellulaire, URA CNRS 1930, Institut Pasteur, 75724 Paris Cedex 15, France
    Mol Cell Biol 20:4532-42. 2000
    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. pmc Systematic deletion of the adenovirus-associated RNAI terminal stem reveals a surprisingly active RNA inhibitor of double-stranded RNA-activated protein kinase
    Ahmed M Wahid
    Manchester Interdisciplinary Biocentre, Faculty of Life Sciences, University of Manchester, Manchester M1 7DN, United Kingdom
    J Biol Chem 283:17485-93. 2008
    ..innate cellular immunity and RNA interference, mediated by the double-stranded RNA-activated protein kinase (PKR) and Dicer/RNA-induced silencing complex, respectively...
  3. pmc Double-stranded RNA-dependent protein kinase activation modulates endotoxin-induced diaphragm weakness
    G S Supinski
    Division of Pulmonary, Critical Care and Sleep Medicine, University of Kentucky, Lexington, Kentucky, USA
    J Appl Physiol (1985) 110:199-205. 2011
    ..It is also known that double-stranded RNA-dependent protein kinase (PKR) is a regulator of caspase-8 activation in neural tissue...
  4. pmc Hepatitis C virus controls interferon production through PKR activation
    Noëlla Arnaud
    Institut Pasteur, Unité Hépacivirus et Immunité Innée, Paris, France
    PLoS ONE 5:e10575. 2010
    ..The cellular protein kinase PKR is an important regulator of translation, through the phosphorylation of its substrate the eIF2alpha initiation ..
  5. pmc TRBP control of PACT-induced phosphorylation of protein kinase R is reversed by stress
    Aïcha Daher
    Virus Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Montreal, Quebec, Canada
    Mol Cell Biol 29:254-65. 2009
    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...
  6. pmc TRAF family proteins link PKR with NF-kappa B activation
    Jesus Gil
    Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Campus Universidad Autonoma, 28049 Madrid, Spain
    Mol Cell Biol 24:4502-12. 2004
    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...
  7. pmc Protein kinase PKR amplification of interferon β induction occurs through initiation factor eIF-2α-mediated translational control
    Christopher S McAllister
    Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California 93106, USA
    J Biol Chem 287:36384-92. 2012
    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-2α...
  8. ncbi The Tat protein of human immunodeficiency virus type 1 is a substrate and inhibitor of the interferon-induced, virally activated protein kinase, PKR
    S R Brand
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11742, USA
    J Biol Chem 272:8388-95. 1997
    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...
  9. pmc The B56alpha regulatory subunit of protein phosphatase 2A is a target for regulation by double-stranded RNA-dependent protein kinase PKR
    Z Xu
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Mol Cell Biol 20:5285-99. 2000
    b>PKR is a cellular serine/threonine kinase that phosphorylates eukaryotic translation initiation factor 2alpha (eIF2alpha) to regulate protein synthesis...
  10. ncbi Binding of double-stranded RNA to protein kinase PKR is required for dimerization and promotes critical autophosphorylation events in the activation loop
    F Zhang
    Laboratory of Gene Regulation and Development, NICHHD, National Institutes of Health, Bethesda, MD 20892, USA
    J Biol Chem 276:24946-58. 2001
    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...
  11. pmc Detection of a novel unglycosylated form of hepatitis C virus E2 envelope protein that is located in the cytosol and interacts with PKR
    Nicole Pavio
    Howard Hughes Medical Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    J Virol 76:1265-72. 2002
    ..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...
  12. ncbi Protein kinase R (PKR) interacts with and activates mitogen-activated protein kinase kinase 6 (MKK6) in response to double-stranded RNA stimulation
    Aristobolo M Silva
    Departments of Cancer Biology and Immunology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 279:37670-6. 2004
    The double-stranded RNA (dsRNA)-activated protein kinase R (PKR) has been invoked in different signaling pathways...
  13. pmc Loss of protein kinase PKR expression in human HeLa cells complements the vaccinia virus E3L deletion mutant phenotype by restoration of viral protein synthesis
    Ping Zhang
    Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA
    J Virol 82:840-8. 2008
    ..Among the cellular proteins implicated as targets of E3L is the protein kinase regulated by RNA (PKR)...
  14. pmc Mechanisms of protein kinase PKR-mediated amplification of beta interferon induction by C protein-deficient measles virus
    Christopher S McAllister
    Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA
    J Virol 84:380-6. 2010
    ..Furthermore, protein kinase PKR and mitochondrial adapter IPS-1 were required for maximal C(ko)-mediated IFN-beta induction, which correlated with ..
  15. ncbi Control of the interferon-induced 68-kilodalton protein kinase by the HIV-1 tat gene product
    S Roy
    Department of Biochemistry, McGill University, Montreal, Canada
    Science 247:1216-9. 1990
    ..effect on translation in vitro by activating the interferon-induced 68-kilodalton protein kinase (p68 kinase)...
  16. ncbi The P58 cellular inhibitor complexes with the interferon-induced, double-stranded RNA-dependent protein kinase, PKR, to regulate its autophosphorylation and activity
    S J Polyak
    Department of Microbiology, School of Medicine, University of Washington, Seattle 98195, USA
    J Biol Chem 271:1702-7. 1996
    ..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. ncbi Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein
    M J Gale
    Department of Microbiology, University of Washington, Seattle 98195, USA
    Virology 230:217-27. 1997
    ..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...
  18. pmc 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
    P R Romano
    Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA
    Mol Cell Biol 18:2282-97. 1998
    The human double-stranded RNA-dependent protein kinase (PKR) is an important component of the interferon response to virus infection...
  19. ncbi Nuclear factor-90 of activated T-cells: A double-stranded RNA-binding protein and substrate for the double-stranded RNA-dependent protein kinase, PKR
    J O Langland
    Department of Microbiology and Division of Molecular and Cellular Biology, Arizona State University, Tempe, Arizona 85287 2701, USA
    Biochemistry 38:6361-8. 1999
    ..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...
  20. pmc Modular structure of PACT: distinct domains for binding and activating PKR
    G A Peters
    Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Mol Cell Biol 21:1908-20. 2001
    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...
  21. pmc Protein kinase PKR is required for platelet-derived growth factor signaling of c-fos gene expression via Erks and Stat3
    A Deb
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    EMBO J 20:2487-96. 2001
    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. ncbi Translation inhibition in apoptosis: caspase-dependent PKR activation and eIF2-alpha phosphorylation
    X Saelens
    Department of Molecular Biology, Unit of Molecular Signaling and Cell Death, Flanders Interuniversity Institute for Biotechnology and Ghent University, 9000 Ghent, Belgium
    J Biol Chem 276:41620-8. 2001
    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...
  23. ncbi Neoplastic progression in melanoma and colon cancer is associated with increased expression and activity of the interferon-inducible protein kinase, PKR
    Steve H Kim
    Department of Surgery, New Jersey Medical School University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, New Jersey, NJ 07103, USA
    Oncogene 21:8741-8. 2002
    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...
  24. pmc 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
    Nicole Pavio
    Howard Hughes Medical Institute, Department of Molecular Microbiology and Immunology, School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    J Virol 77:3578-85. 2003
    ..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)...
  25. ncbi Nucleophosmin interacts with and inhibits the catalytic function of eukaryotic initiation factor 2 kinase PKR
    Qishen Pang
    OHSU Cancer Institute, Schools of Medicine and Dentistry, Oregon Health Sciences University, Portland, OR 97201, USA
    J Biol Chem 278:41709-17. 2003
    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...
  26. ncbi Protein kinase R is increased and is functional in hepatitis C virus-related hepatocellular carcinoma
    Yoichi Hiasa
    Gastrointestinal Unit, Cancer Center and Hospital for Children, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Am J Gastroenterol 98:2528-34. 2003
    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...
  27. ncbi The dsRNA protein kinase PKR: virus and cell control
    M A Garcia
    Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, CSIC, Ciudad Universitaria Cantoblanco, 28049 Madrid, Spain
    Biochimie 89:799-811. 2007
    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 ..
  28. pmc Protein kinase PKR plays a stimulus- and virus-dependent role in apoptotic death and virus multiplication in human cells
    Ping Zhang
    Department of Molecular, Cellular and Developmental Biology and Biomolecular Sciences and Engineering Program, University of California, Santa Barbara, CA 93106, USA
    J Virol 81:8192-200. 2007
    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 ..
  29. pmc Sendai virus C protein plays a role in restricting PKR activation by limiting the generation of intracellular double-stranded RNA
    Kenji Takeuchi
    Division of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical Science, Seta, Otsu, Shiga 520 2192, Japan
    J Virol 82:10102-10. 2008
    ..caused phosphorylation of both the translation initiation factor eIF2alpha and dsRNA-dependent protein kinase (PKR)...
  30. pmc Induction of protein kinase PKR-dependent activation of interferon regulatory factor 3 by vaccinia virus occurs through adapter IPS-1 signaling
    Ping Zhang
    Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California 93106, USA
    J Biol Chem 283:34580-7. 2008
    ..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 ..
  31. pmc Protein kinase PKR mediates the apoptosis induction and growth restriction phenotypes of C protein-deficient measles virus
    Ann M Toth
    Department of Molecular, University of California, Santa Barbara, California 93106, USA
    J Virol 83:961-8. 2009
    ..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), ..
  32. doi Stress-induced phosphorylation of PACT reduces its interaction with TRBP and leads to PKR activation
    Madhurima Singh
    Department of Biological Sciences, Developmental Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29208, USA
    Biochemistry 50:4550-60. 2011
    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...
  33. pmc PKR-dependent mechanisms of interferon-α for inhibiting hepatitis B virus replication
    Il Hyun Park
    School of Life Sciences and Biotechnology, Korea University, Seoul 136 701, Korea
    Mol Cells 32:167-72. 2011
    ..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...
  34. doi Oxidative stress increases BACE1 protein levels through activation of the PKR-eIF2α pathway
    François Mouton-Liger
    Service d Histologie et de Biologie du Vieillissement, APHP, groupe hospitalier Lariboisière Fernand Widal Saint Louis, Universite Paris VII, Paris, France
    Biochim Biophys Acta 1822:885-96. 2012
    ..b>PKR (double-stranded RNA dependant protein kinase) is a pro-apoptotic kinase that phosphorylates eIF2α and modulates ..
  35. doi Increased interaction between PACT molecules in response to stress signals is required for PKR activation
    Madhurima Singh
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    J Cell Biochem 113:2754-64. 2012
    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...
  36. ncbi 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
    S J McCormack
    Department of Biological Sciences, University of California, Santa Barbara 93106
    Virology 188:47-56. 1992
    ....
  37. ncbi HIV-1 Tat directly interacts with the interferon-induced, double-stranded RNA-dependent kinase, PKR
    N A McMillan
    Department of Cancer Biology, Cleveland Clinic Foundation, Ohio 44195, USA
    Virology 213:413-24. 1995
    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...
  38. pmc Autophosphorylation sites participate in the activation of the double-stranded-RNA-activated protein kinase PKR
    D R Taylor
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Mol Cell Biol 16:6295-302. 1996
    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...
  39. pmc PACT, a protein activator of the interferon-induced protein kinase, PKR
    R C Patel
    Department of Molecular Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, OH 44195, USA
    EMBO J 17:4379-90. 1998
    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...
  40. pmc Structure of the double-stranded RNA-binding domain of the protein kinase PKR reveals the molecular basis of its dsRNA-mediated activation
    S Nanduri
    Structural Biology Program, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    EMBO J 17:5458-65. 1998
    Protein kinase PKR is an interferon-induced enzyme that plays a key role in the control of viral infections and cellular homeostasis...
  41. ncbi Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein
    D R Taylor
    Department of Molecular Microbiology and Immunology and Howard Hughes Medical Institute, University of Southern California, School of Medicine, Los Angeles, CA 90089, USA
    Science 285:107-10. 1999
    ..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...
  42. ncbi PKR; a sentinel kinase for cellular stress
    B R Williams
    Department of Cancer Biology NB40, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio, OH 44195, USA
    Oncogene 18:6112-20. 1999
    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...
  43. ncbi HIV-I TAT inhibits PKR activity by both RNA-dependent and RNA-independent mechanisms
    R Cai
    Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Arch Biochem Biophys 373:361-7. 2000
    ..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...
  44. ncbi Activation of NF-kappa B by the dsRNA-dependent protein kinase, PKR involves the I kappa B kinase complex
    J Gil
    Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, CSIC, Campus Universidad Autonoma, 28049 Madrid, Spain
    Oncogene 19:1369-78. 2000
    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...
  45. ncbi 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
    A Daher
    Molecular Oncology Group McGill AIDS Centre, Lady Davis Institute for Medical Research, 3755 Cote Ste Catherine, Montreal H3T 1E2, Quebec, Canada
    J Biol Chem 276:33899-905. 2001
    ..TRBP interacts with the interferon-induced protein kinase R (PKR) and inhibits its activity...
  46. pmc The Hsp90 chaperone complex is both a facilitator and a repressor of the dsRNA-dependent kinase PKR
    O Donze
    Departement de Biologie Cellulaire, Universite de Geneve, Sciences III, 30 Quai Ernest Ansermet, CH 1211 Geneve 4, Switzerland
    EMBO J 20:3771-80. 2001
    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...
  47. ncbi Protein kinase R regulates double-stranded RNA induction of TNF-alpha but not IL-1 beta mRNA in human epithelial cells
    Tiffany R Meusel
    Division of Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Asthma and Allergy Center, Baltimore, MD 21224, USA
    J Immunol 168:6429-35. 2002
    ..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...
  48. pmc An RNA-dependent protein kinase is involved in tunicamycin-induced apoptosis and Alzheimer's disease
    Reiko Onuki
    Gene Function Research Center, National Institute of Advanced Industrial Science and Technology, Higashi, Tsukuba Science City, Japan
    EMBO J 23:959-68. 2004
    ..We identified a double-stranded RNA-dependent protein kinase (PKR) as one of the participants in this process...
  49. ncbi Loss of PKR activity in chronic lymphocytic leukemia
    Su Ing Hii
    Cancer Biology Programme, Centre for Immunology and Cancer Research, University of Queensland, Brisbane, Australia
    Int J Cancer 109:329-35. 2004
    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 ..
  50. ncbi Reduction of double-stranded RNA-activated protein kinase in hepatocellular carcinoma associated with hepatitis B virus
    George G Chen
    Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, N T Hong Kong
    J Med Virol 73:187-94. 2004
    ..Double-stranded RNA (dsRNA)-activated protein kinase (PKR) is an interferon-induced, serine/threonine protein kinase...
  51. pmc Phosphorylation of HIV Tat by PKR increases interaction with TAR RNA and enhances transcription
    Liliana Endo-Munoz
    Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia
    Virol J 2:17. 2005
    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 ..
  52. ncbi Thr 446 phosphorylation of PKR by HCV core protein deregulates G2/M phase in HCC cells
    A Alisi
    Dipartimento di Medicina Interna e Sanità Pubblica M I S P, University of L Aquila, L Aquila, Italy
    J Cell Physiol 205:25-31. 2005
    ..Different pathways mediate G2/M arrest: such as p53 and double strand RNA protein kinase (PKR)...
  53. ncbi Expression of double-stranded RNA-activated protein kinase in small-size peripheral adenocarcinoma of the lung
    Mee Sook Roh
    Medical Research Center for Cancer Molecular Therapy, Dong A University College of Medicine, Busan, Korea
    Pathol Int 55:688-93. 2005
    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 ..
  54. pmc Antiviral action of the tumor suppressor ARF
    Maria A Garcia
    Centro Nacional de Biotecnología CNB, Universidad Autonoma de Madrid, Madrid, Spain
    EMBO J 25:4284-92. 2006
    ..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...
  55. ncbi Phosphorylated PKR contributes the induction of GRP94 under ER stress
    Mototsugu Ito
    Graduate School of Pharmaceutical Science, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 13 0033, Japan
    Biochem Biophys Res Commun 360:615-20. 2007
    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...
  56. pmc West Nile virus-induced interferon production is mediated by the double-stranded RNA-dependent protein kinase PKR
    Felicia D Gilfoy
    Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555 0436, USA
    J Virol 81:11148-58. 2007
    ..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 ..
  57. ncbi The double-strand RNA-dependent protein kinase PKR plays a significant role in a sustained ER stress-induced apoptosis
    Eun Soo Lee
    Department of Biological Science, Sungkyunkwan University, Cheoncheon Dong 300, Jangan gu, Suwon, Gyeonggi do 440 746, South Korea
    FEBS Lett 581:4325-32. 2007
    ..Here, we demonstrate that the double strand RNA-dependent protein kinase (PKR) is involved in the ER stress-mediated signaling pathway...
  58. pmc Interaction of human tRNA-dihydrouridine synthase-2 with interferon-induced protein kinase PKR
    Megan Mittelstadt
    Department of Biological Sciences, University of South Carolina Columbia, SC 29208, USA
    Nucleic Acids Res 36:998-1008. 2008
    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...
  59. pmc Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection
    Margherita Doria
    Laboratory of Immunoinfectivology, Children s Hospital Bambino Gesu, 00165, Rome, Italy
    Nucleic Acids Res 37:5848-58. 2009
    ..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...
  60. pmc 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
    Xiaoxing Wang
    Institute of Molecular and Cell Biology, Proteos, Singapore
    J Virol 83:12462-72. 2009
    ..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 ..
  61. doi Novel role for the double-stranded RNA-activated protein kinase PKR: modulation of macrophage infection by the protozoan parasite Leishmania
    Renata M S Pereira
    Laboratorio de Parasitologia Molecular, Instituto de Biofisica Carlos Chagas Filho, Centro de Ciencias da Saude, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
    FASEB J 24:617-26. 2010
    ..Double-stranded RNA (dsRNA)-activated protein kinase R (PKR), a classic antiviral protein, is able to regulate a number of signaling pathways and macrophage ..
  62. pmc Hepatitis C virus blocks interferon effector function by inducing protein kinase R phosphorylation
    Urtzi Garaigorta
    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
    Cell Host Microbe 6:513-22. 2009
    ..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 ..
  63. pmc Regulation of PKR by HCV IRES RNA: importance of domain II and NS5A
    Rebecca Toroney
    Department of Chemistry, Pennsylvania State University, 104 Chemistry Building, University Park, PA 16802, USA
    J Mol Biol 400:393-412. 2010
    b>Protein kinase R (PKR) is an essential component of the innate immune response...
  64. pmc Prognostic significance of RNA-dependent protein kinase on non-small cell lung cancer patients
    Abujiang Pataer
    Department of Thoracic and Cardiovascular Surgery, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Clin Cancer Res 16:5522-8. 2010
    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...
  65. doi Multiple levels of PKR inhibition during HIV-1 replication
    Guerline Clerzius
    Lady Davis Institute for Medical Research, Montreal, QC, Canada
    Rev Med Virol 21:42-53. 2011
    ..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...
  66. pmc Hepatitis C virus reveals a novel early control in acute immune response
    Noëlla Arnaud
    Institut Pasteur, Hepacivirus and Innate Immunity, Paris, France
    PLoS Pathog 7:e1002289. 2011
    ..by cleaving MAVS through its NS3/4A protease and by controlling cellular translation through activation of PKR, an eIF2α-kinase containing dsRNA-binding domains (DRBD)...
  67. doi Increased cerebrospinal fluid levels of double-stranded RNA-dependant protein kinase in Alzheimer's disease
    François Mouton-Liger
    Memory Clinical Center, Lariboisiere Fernand Widal Saint Louis Hospital, Assistance Publique Hopitaux de Paris, University of Paris Diderot, France
    Biol Psychiatry 71:829-35. 2012
    ..The proapoptotic kinase R (PKR), is activated by Aβ accumulates in degenerating neurons in AD brains and controls protein synthesis and ..
  68. pmc 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
    Masmudur M Rahman
    Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America
    PLoS Pathog 9:e1003465. 2013
    ..Using proteomic approaches, we have identified Protein Kinase R (PKR) and RNA helicase A (RHA)/DHX9 as two cellular binding partners of M029 protein...
  69. ncbi Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon
    E Meurs
    Institut Pasteur Unité d Oncologie Virale URA CNRS 1157, Paris, France
    Cell 62:379-90. 1990
    The double-stranded (ds) RNA-activated protein kinase from human cells is a 68 kd protein (p68 kinase) induced by interferon...
  70. pmc NF-kappaB activation by double-stranded-RNA-activated protein kinase (PKR) is mediated through NF-kappaB-inducing kinase and IkappaB kinase
    M Zamanian-Daryoush
    Department of Cancer Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Mol Cell Biol 20:1278-90. 2000
    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...
  71. ncbi Nuclear factor 90 is a substrate and regulator of the eukaryotic initiation factor 2 kinase double-stranded RNA-activated protein kinase
    L M Parker
    Department of Biochemistry and Molecular Biology, New Jersey Medical School, University of Medicine and Dentistry, New Jersey, Newark, New Jersey 07103 2714, USA
    J Biol Chem 276:32522-30. 2001
    ..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...
  72. ncbi Double-stranded RNA-activated protein kinase interacts with apoptosis signal-regulating kinase 1. Implications for apoptosis signaling pathways
    Takenori Takizawa
    Department of Biochemistry, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan
    Eur J Biochem 269:6126-32. 2002
    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...
  73. ncbi Okadaic acid induces apoptosis through double-stranded RNA-dependent protein kinase/eukaryotic initiation factor-2alpha pathway in human osteoblastic MG63 cells
    Hiroyuki Morimoto
    Department of Anatomy, School of Dentistry, The University of Tokushima, Kuramoto, Tokushima 770 8504, Japan
    J Biochem 136:433-8. 2004
    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...
  74. ncbi 5'-triphosphate-dependent activation of PKR by RNAs with short stem-loops
    Subba Rao Nallagatla
    Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA
    Science 318:1455-8. 2007
    ..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...
  75. doi PKR protein kinase is activated by hepatitis C virus and inhibits viral replication through translational control
    Ju Il Kang
    School of Life Sciences and Biotechnology, Korea University, 5 1 Anamdong, Seoul 136 701, Republic of Korea
    Virus Res 142:51-6. 2009
    ..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...
  76. pmc Repression of PKR mediates palmitate-induced apoptosis in HepG2 cells through regulation of Bcl-2
    Xuerui Yang
    Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824, USA
    Cell Res 19:469-86. 2009
    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)...
  77. pmc The RNA-activated protein kinase enhances the induction of interferon-beta and apoptosis mediated by cytoplasmic RNA sensors
    Christopher S McAllister
    Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California 93106, USA
    J Biol Chem 284:1644-51. 2009
    ..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 ..
  78. ncbi Characterization of transgenic mice with targeted disruption of the catalytic domain of the double-stranded RNA-dependent protein kinase, PKR
    N Abraham
    Ottawa Regional Cancer Center Research Laboratories, Ottawa, Ontario K1H 8L6
    J Biol Chem 274:5953-62. 1999
    The interferon-inducible, double-stranded RNA-dependent protein kinase PKR has been implicated in anti-viral, anti-tumor, and apoptotic responses...
  79. pmc A PKR-like eukaryotic initiation factor 2alpha kinase from zebrafish contains Z-DNA binding domains instead of dsRNA binding domains
    Stefan Rothenburg
    Institut fur Immunologie, Universitätsklinikum Eppendorf, 20246 Hamburg, Germany
    Proc Natl Acad Sci U S A 102:1602-7. 2005
    The double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is induced as part of the IFN response in mammals and acts to shut down protein synthesis by the phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha)...
  80. ncbi The catalytic activity of the eukaryotic initiation factor-2alpha kinase PKR is required to negatively regulate Stat1 and Stat3 via activation of the T-cell protein-tyrosine phosphatase
    Shuo Wang
    Department of Oncology, Sir Mortimer B Davis Jewish General Hospital, Montreal, Quebec, Canada
    J Biol Chem 281:9439-49. 2006
    ..The protein kinase PKR plays an important role in translational control through the modulation of eukaryotic initiation factor-2alpha ..
  81. pmc The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activa
    B He
    Marjorie B Kovler Viral Oncology Laboratories, University of Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 94:843-8. 1997
    In human cells infected with herpes simplex virus 1 the double-stranded RNA-dependent protein kinase (PKR) is activated but phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2) and total shutoff of ..
  82. pmc Interleukin 3 stimulates protein synthesis by regulating double-stranded RNA-dependent protein kinase
    T Ito
    Johns Hopkins Oncology Center, Baltimore, MD 21231
    Proc Natl Acad Sci U S A 91:7455-9. 1994
    ..line, IL-3 deprivation resulted in increased autophosphorylation of double-stranded RNA-dependent protein kinase (PKR) that has been reported to inhibit protein synthesis by phosphorylating the alpha subunit of eukaryotic initiation ..
  83. ncbi Comparison of the eIF-2alpha homologous proteins of seven ranaviruses (Iridoviridae)
    S Essbauer
    Institute of Zoology, Fishery Biology and Fish Diseases, LMU University of Munich, Muenchen, Germany
    Virus Genes 23:347-59. 2001
    ..stress such as viral infections, eIF-2alpha is phosphorylated by double-stranded RNA-dependent protein kinase (PKR) leading to the inhibition of cellular protein synthesis...
  84. ncbi Inactivation of the PKR protein kinase and stimulation of mRNA translation by the cellular co-chaperone P58(IPK) does not require J domain function
    Wei Yan
    Department of Microbiology and Washington Regional Primate Research Center, University of Washington, Seattle, Washington 98195, USA
    Biochemistry 41:4938-45. 2002
    P58(IPK) was discovered as an inhibitor of the interferon-induced, protein kinase, PKR. Upon virus infection, PKR can, as part of the host defense system, inhibit mRNA translation by phosphorylating the alpha subunit of protein synthesis ..
  85. pmc NSs protein of rift valley fever virus induces the specific degradation of the double-stranded RNA-dependent protein kinase
    Matthias Habjan
    Department of Virology, University of Freiburg, Freiburg, Germany
    J Virol 83:4365-75. 2009
    ..part of the antiviral activity of IFN against RVFV is due to a double-stranded RNA-dependent protein kinase (PKR)...
  86. ncbi Involvement of double-stranded RNA-dependent protein kinase in ER stress-induced retinal neuron damage
    Masamitsu Shimazawa
    Department of Biofunctional Molecules, Gifu Pharmaceutical University, Gifu, Japan
    Invest Ophthalmol Vis Sci 48:3729-36. 2007
    To clarify whether the activation of double-stranded RNA-dependent protein kinase (PKR) participates in the cell death induced by endoplasmic reticulum (ER) stress, the authors used cultured retinal ganglion cells (RGC-5, a rat ganglion ..
  87. ncbi Platelet-derived growth factor signal transduction through the interferon-inducible kinase PKR. Immediate early gene induction
    L J Mundschau
    Cancer Research Center, Boston University School of Medicine, Massachusetts 02118
    J Biol Chem 270:3100-6. 1995
    The interferon-inducible, double-stranded RNA (dsRNA)-dependent eukaryotic initiation factor-2 alpha kinase PKR has primarily been characterized as a component of the interferon-mediated cellular antiviral response...
  88. doi Double-stranded RNA-activated protein kinase inhibits hepatitis C virus replication but may be not essential in interferon treatment
    Jin Hai Chang
    Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
    Liver Int 30:311-8. 2010
    Double-stranded RNA-activated protein kinase (PKR), an interferon (IFN)-stimulated gene, is activated by binding with double-stranded RNA, a putative replicative intermediate of the hepatitis C virus (HCV)...
  89. doi Double stranded RNA-dependent protein kinase is involved in osteoclast differentiation of RAW264.7 cells in vitro
    Junpei Teramachi
    Department of Histology and Oral Histology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima 770 8504, Japan
    Exp Cell Res 316:3254-62. 2010
    Double-stranded RNA-dependent protein kinase (PKR) plays a critical role in antiviral defence of the host cells. PKR is also involved in cell cycle progression, cell proliferation, cell differentiation, tumorigenesis, and apoptosis...
  90. ncbi The double-stranded RNA-activated protein kinase mediates radiation resistance in mouse embryo fibroblasts through nuclear factor kappaB and Akt activation
    Urs von Holzen
    Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 13:6032-9. 2007
    Activation of the double-stranded RNA-activated protein kinase (PKR) leads to the induction of various pathways including the down-regulation of translation through phosphorylation of the eukaryotic translation initiation factor 2alpha (..
  91. pmc Ethanol promotes thiamine deficiency-induced neuronal death: involvement of double-stranded RNA-activated protein kinase
    Zun Ji Ke
    Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Alcohol Clin Exp Res 33:1097-103. 2009
    ..The double-stranded RNA-activated protein kinase (PKR) is a potent antiviral protein...
  92. pmc Translational resistance of late alphavirus mRNA to eIF2alpha phosphorylation: a strategy to overcome the antiviral effect of protein kinase PKR
    Iván Ventoso
    Departamento de Biologia Molecular y Celular, Centro Nacional de Biotecnologia CSIC, Cantoblanco, E 28049 Madrid, Spain
    Genes Dev 20:87-100. 2006
    The double-stranded RNA-dependent protein kinase (PKR) is one of the four mammalian kinases that phosphorylates the translation initiation factor 2alpha in response to virus infection...
  93. doi Functional expression of double-stranded RNA-dependent protein kinase in rat intestinal epithelial cells
    Nagahiro Sato
    Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, 1 1, Iseigaoka, Yahatanishi, Kitakyushu 807 8555, Japan
    J Cell Biochem 110:104-11. 2010
    ..component of this barrier in intestine, we examined the expression of double-stranded RNA-dependent protein kinase (PKR)...
  94. ncbi Induction of E-selectin expression by double-stranded RNA and TNF-alpha is attenuated in murine aortic endothelial cells derived from double-stranded RNA-activated kinase (PKR)-null mice
    S K Bandyopadhyay
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    J Immunol 164:2077-83. 2000
    ..Because we have previously shown that the dsRNA-activated kinase PKR mediates dsRNA induction of NF-kappaB, we used murine aortic endothelial (MuAE) cells isolated from wild-type and ..
  95. ncbi Double-stranded RNA-dependent protein kinase (pkr) is essential for thermotolerance, accumulation of HSP70, and stabilization of ARE-containing HSP70 mRNA during stress
    Meijuan Zhao
    Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 277:44539-47. 2002
    We have investigated the role of the double-stranded RNA-dependent protein kinase gene (pkr) in the regulation of the heat shock response...
  96. doi Activation of eukaryotic initiation factor-2 α-kinases in okadaic acid-treated neurons
    S M Kim
    Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Korea
    Neuroscience 169:1831-9. 2010
    ..and this protein can be phosphorylated by several kinases, including double-stranded RNA-dependent protein kinase (PKR), PKR-like endoplasmic reticulum kinase (PERK), amino acids-regulated eIF2 alpha kinase (GCN2) and heme-regulated ..
  97. ncbi Ultrastructural localization of interferon-inducible double-stranded RNA-activated enzymes in human cells
    S Besse
    Laboratoire Organisation Fonctionnelle du Noyau de l UPR 9044 CNRS, Villejuif, France
    Exp Cell Res 239:379-92. 1998
    The protein kinase PKR and the 2',5'-oligoadenylate (2-5A) synthetase are two interferon-induced and double-stranded RNA-activated enzymes which are implicated in the mechanism of action of interferon...
  98. ncbi Upstream signaling pathways leading to the activation of double-stranded RNA-dependent serine/threonine protein kinase in beta-amyloid peptide neurotoxicity
    Ka Chun Suen
    Laboratory of Neurodegenerative Diseases, Department of Anatomy, Faculty of Medicine, The University of Hong Kong, Hong Kong
    J Biol Chem 278:49819-27. 2003
    ..previously that Abeta peptide induces activation of double-stranded RNA-dependent serine/threonine protein kinase (PKR) and phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) in neurons in vitro...
  99. ncbi Double-stranded RNA-activated protein kinase is required for the LPS-induced activation of STAT1 inflammatory signaling in rat brain glial cells
    Jee Hoon Lee
    Department of Pharmacology, Ajou University School of Medicine, Suwon, Korea
    Glia 50:66-79. 2005
    b>PKR, the double-stranded RNA (dsRNA)-activated serine/threonine kinase, has been implicated as an important component of host responses to infection and various situations of cellular stress...
  100. ncbi Activation of double-stranded RNA-activated protein kinase by mild impairment of oxidative metabolism in neurons
    Xin Wang
    Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    J Neurochem 103:2380-90. 2007
    ..The double-stranded RNA-activated protein kinase (PKR), has been well known for its anti-viral function...
  101. pmc Functional domains and the antiviral effect of the double-stranded RNA-dependent protein kinase PKR from Paralichthys olivaceus
    Rong Zhu
    State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
    J Virol 82:6889-901. 2008
    The double-stranded RNA (dsRNA)-dependent protein kinase PKR is thought to mediate a conserved antiviral pathway by inhibiting viral protein synthesis via the phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (..

Research Grants64

  1. Suppression of the Interferon Response by the Hepatitis C Virus
    FRANCIS VINCENT CHISARI; Fiscal Year: 2010
    ..Importantly, the kinetics of this effect coincided with HCV-induced phosphorylation of protein kinase R (PKR) and its substrate eIF2? which must be hypophosphorylated to support capped mRNA translation...
  2. TRANSLATIONAL CONTROL IN REGULATION OF APOPTOSIS
    Randal Kaufman; Fiscal Year: 2002
    ..ubiquitous eIF-2alpha kinase known in mammalian cells is the double-stranded RNA-dependent serine/threonine kinase (PKR)...
  3. The Role of PKR in a Novel IL-3 Signal Transduction Pathway
    William Stratford May; Fiscal Year: 2012
    ..chemotherapy treatment or viral infection promotes activation of the double-stranded RNA dependent protein kinase, PKR, by its cellular activator protein, RAX...
  4. Cigarette Smoke, RIG-like Helicases and Alveolar Remodeling
    Jack A Elias; Fiscal Year: 2012
    ..is downstream of RLH and includes type I and II Interferons, IL-18, double-Stranded RNA-Dependent Protein Kinase (PKR) and eukaryotic initiation factor- 2[unreadable] (eIF2[unreadable]) and (c) associated with activation of the 2&..
  5. Charles E Samuel; Fiscal Year: 2014
    ..of the proposed investigation is to elucidate the roles of the interferon-inducible RNA-regulated protein kinase (PKR) in the actions that interferons (IFN) mediate on viral and host functions...
  6. Molecular Insights into Activation and Substrate Recognition of Protein Kinase R
    Madhusudan Dey; Fiscal Year: 2012
    ..PUBLIC HEALTH RELEVANCE: Project Narrative: Protein kinase R is directly involved in anti-viral defense responses and anti-proliferative effects on cancer cells, this ..
  7. Tracy G Anthony; Fiscal Year: 2015
    ..to asparaginase and enhances endoplasmic reticulum (ER) stress, leading to induction of another eIF2 kinase called PKR-like ER- resident Kinase (PERK)...
  8. James L Cole; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): The RNA-activated protein kinase, PKR, is induced by interferon and plays a pivotal role in the innate immunity response to viral infection...
  9. Trichothecene Toxicity and the Ribotoxic Stress Response
    James J Pestka; Fiscal Year: 2012
    ..trichothecene, mediates cleavage of 18S and 28S ribosomal (r)RNA, 2) double-stranded RNA-activated protein kinase (PKR), a ribosome-associated serine-threonine kinase, is essential for DON-induced protein kinase activation and 3) DON ..
  10. YPE PETER DE JONG; Fiscal Year: 2015
    ..In order to interfere downstream from the interferon response, HCV activates PKR, which leads to translational down-regulation of interferon stimulated genes (ISGs) through activation of eIF21...
  11. Viral elements of HSV maturation
    Bin He; Fiscal Year: 2010
    ..5 is to block the interferon response mediated by double-stranded RNA dependent protein kinase PKR. In addition, gamma 134.5 is involved in virus egress. This activity maps to the amino-terminus of gamma 134...
  12. Bertal H Aktas; Fiscal Year: 2015
    ..Translation initiation is inhibited through activation of protein kinase R (PKR)-like ER resident kinase PERK and phosphorylation of eukaryotic translation initiation factor 2 aplha (..
  13. MOLECULAR EVENTS IN THE PATHOGENESIS OF KAPOSI'S SARCOMA
    Margaret Offermann; Fiscal Year: 1999
    ..This is most likely due to differential activation of the double stranded RNA activated protein kinase, PKR...
  14. Gang Chen; Fiscal Year: 2016
    ..The double-stranded RNA (dsRNA)-activated protein kinase (PKR) organizes the cellular self-defense system in response to diverse physiochemical stresses or viral infection by ..
  15. John D Bartlett; Fiscal Year: 2016
    ..of initiating stress, eIF2a can be phosphorylated by any one of four different kinases -- Gcn2 (Eif2ak4), Hri (Eif2ak1), Perk (Eif2ak3), and Pkr (Eif2ak2) - each of which responds to different stress stimuli...
  16. Innate Immune Recognition Enhances Flavivirus Vaccine Efficacy
    Gregg N Milligan; Fiscal Year: 2010
    ..These studies showed that protein kinase R (PKR) appeared to be acting as a pattern-recognition receptor (PRR) that triggered IFN synthesis...
  17. Structural studies of PKR regulation by viral non-coding RNA
    GRAEME LESLIE CONN; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): PKR is a key component of the cellular innate immune response against viral or bacterial infection and is an important mediator and integrator of signals that control other diverse cellular processes ..
  18. Infection with Bordetella pertussis exacerbates Influenza infection
    VICTOR ISAAC AYALA; Fiscal Year: 2010
    ..Lastly we will examine gene expression for five IFN stimulated genes: protein kinase PKR, 2 ,5 -Oligoadenylate Synthetase, RNaseL, Adenosine deaminase (ADAR1) and MX protien GTPase by RT-PCR...
  19. Regulation of PKR by Novel RNA Motifs
    Philip C Bevilacqua; Fiscal Year: 2012
    ..is to uncover roles for RNA structure in regulating biological activity of the RNA-activated protein kinase, PKR. Viral and cellular RNAs fold into diverse secondary and tertiary structures and interact with proteins to alter ..
  20. Adam P Geballe; Fiscal Year: 2016
    ..why hTRS1 is essential for the virus, how it functions, and how it has adapted to the changes in the cellular protein kinase R (PKR) pathway that have occurred repeatedly during primate evolution...
  21. Gokhan S Hotamisligil; Fiscal Year: 2016
    ..led us to a well-established pathogen sensing pathway mediated by the double-stranded RNA dependent protein kinase, PKR. We made exiting observations showing the marked activation of this kinase, which can act upstream of JNK and the ..
  22. Cell-based assay for high-throughput screening of TLR3 activators
    Tsung Hsien Chuang; Fiscal Year: 2010
    ..lack specificity and are recognized by multiple cellular targets including RIG-I-like receptors and protein kinase PKR, in addition to the TLR3. This could explain, at least in part, the adverse effects of these dsRNAs...
  23. The Role of Microglia during TMEV-IDD in the Adult Mouse
    DANNE S DUNCAN; Fiscal Year: 2010
    ..Since, both TLR3 and PKR (pattern recognition receptors-PRRs) recognize viral double-stranded RNA, these molecules are most relevant for ..
  24. Carl F Nathan; Fiscal Year: 2014
    ..This project explores a work-around for resistance of M. tuberculosis (Mtb) to anti-infectives: inhibiting protein kinase R (PKR) in the host. Mtb depends on PKR to cause full-blown disease...
  25. Role of ASK1 and PKR in Fancc hematopoiesis
    Laura Haneline; Fiscal Year: 2009
    ..the other was to enhance survival after IFN-y/TNF-a treatment by inhibiting double-stranded RNA-dependent kinase (PKR)-mediated apoptosis...
  26. Alcohol-Induced Regulation of Hepatic Protein Synthesis
    THOMAS VARY; Fiscal Year: 2007
    ..Ethanol or its metabolites may cause a selective activation of 1 of the known elF2 kinases (PERK, GCN2, PKR or HRI) or inhibit elF2a phosphatase activity...
  27. Heat shock protein 90 antagonist-based therapy of mantle cell lymphoma
    Kapil Bhalla; Fiscal Year: 2012
    ..Additionally, GAA treatment depleted the mediators of endoplasmic reticulum (ER) stress PKR and IRE-11. Treatment with hydroxamic acid analogue (HA) pan-histone deacetylase inhibitor (HDI), e.g...
  28. ANTIVIRAL PROTEIN KINASE AND TH2 RESPONSES
    Farhad Imani; Fiscal Year: 2002
    ..which consequently activates a ubiquitous anti viral protein kinase (Protein Kinase double-stranded RNA-activated, PKR)...
  29. Mark R Schleiss; Fiscal Year: 2015
    ..by targeting viral genes that subvert two key host defenses: MHC I homolog genes (NK cell evasins) and protein kinase R (PKR) evasins...
  30. Molecular Basis for PKR Activation by Viral RNAs
    JOSEPH PUGLISI; Fiscal Year: 2009
    ..Double-stranded RNA dependent protein kinase (PKR) is a 68 kDa protein that is activated by dsRNA binding, leading to phosphorylation of initiation factor elF2a...
  31. IL-17-Induced Regulation of C/EBPbeta
    MICHELLE ROSAN SIMPSON-ABELSON; Fiscal Year: 2012
    ..i) the role of an upstream open reading frame (uORF) within C/EBP?, and (ii) the role of the PI3K/AKT/mTOR and PKR signaling pathways in IL-17-mediated C/EBP? alternative translation...
  32. RNA-regulation and signal transduction by PKR
    CYNTHIA BURROWS; Fiscal Year: 2006
    DESCRIPTION (provided by applicant): PKR, the RNA-dependent protein kinase, is a member of the elF2 alpha kinase family that controls the rate of translation initiation in human cells in response to various environmental stresses...
  33. VIRUS/HOST INTERACTIONS MODULATED BY HEPATITIC C VIRUS
    Radhakrishnan Padmanabhan; Fiscal Year: 2001
    ..of these kinases has been identified to be interferon (IFN)-inducible double-stranded RNA activated protein kinase (PKR) and the identity of other kinase(s) is unknown...
  34. HOW ENVIRONMENTAL CHEMICALS IMPAIR IMMUNITY
    David Sherr; Fiscal Year: 2009
    ..1): We will: a) determine the role of death receptors in caspase-8 activation, b) evaluate the contribution of JNK, PKR, and ASK1 kinases to caspase-8-dependent apoptosis, and c) identify components of activated caspase-8 complexes by ..
  35. James C Alwine; Fiscal Year: 2015
    ..Adipocyte differentiation and the activation of lipogenic genes have previously been shown to be mediated by PKR-like endoplasmic reticulum kinase (PERK), an ER-resident sensor that is activated by endoplasmic reticulum stress, ..
  36. David J Pintel; Fiscal Year: 2015
    ..Our finding that Ad VA RNA mutants that could no longer inactivate the dsRNA- activated protein kinase R (PKR) could not support AAV replication led to our discovery of an element within the AAV capsid coding mRNA ..
  37. Role of Prokineticin 2 in Cerebral Ischemia
    Michelle Y Cheng; Fiscal Year: 2010
    ..of PK2 post- ischemia resulted in an increased infarct volume, and blocking the PK2 receptor with an antagonist (PKR-A) reduced infarct volume...
  38. Treatment of Speech Disorders in Children with Down Syndrome
    Stephen Camarata; Fiscal Year: 2009
    ..be randomly assigned to one of two treatments designed to improve speech skills: Phonological Knowledge Recast (PKR) treatment or Articulatory Training (AT) treatment...
  39. HERPES SIMPLEX VIRUS INFECTION AND CELLULAR RESPONSE
    Bin He; Fiscal Year: 2004
    ..It has been established that virus infection activates the double-stranded RNA dependent protein kinase (PKR), which phosphorylates the alpha subunit of translation initiation factor 2 (eIF-2alpha), leading to the shutoff of ..
  40. Evolutionary potential of a model poxvirus
    Nels C Elde; Fiscal Year: 2013
    ..and evolution of a fast evolving poxvirus protein called K3L that mimics the substrate ofthe anti-viral Protein kinase R (PKR) to disrupt anti-viral activity...
  41. PROTEIN SYNTHESIS INITIATION IN ANIMAL CELLS
    Bansidhar Datta; Fiscal Year: 2002
    ..p67, a cellular glycoprotein, protects eIF2alpha from phosphorylation by active kinases, PKR and HCR. The O-GlcNAc moieties of p67 are required for its activity...
  42. Mechanisms of Trichothecene Toxicity
    James Pestka; Fiscal Year: 2005
    ..Our central hypothesis is that double stranded RNA-activated protein kinase (PKR) and hematopoietic cell kinase (Hck) are critical for trichothecene-induced p38 activation and downstream toxicity...
  43. Mauro Costa-Mattioli; Fiscal Year: 2016
    ..new treatments for conditions associated with memory loss such as aging, Alzheimer's disease, and Huntington's disease, all conditions where PKR activity is abnormally elevated and GABAergic synaptic transmission is altered.
  44. Activation of Innate Immunity by Small Ribonucleoprotein
    Westley Reeves; Fiscal Year: 2007
    ..innate immunity by binding to dsRNA binding proteins such as TLR3 and/or the dsRNA dependent protein kinase (PKR), causing increased production of type I interferon (IFN) leading to an antiviral response...
  45. Intrahepatic IRF-3 and NF-kB Signaling and Interferon Responses in Hepatitis C
    Stanley M Lemon; Fiscal Year: 2010
    ..of IFN and proinflammatory cytokines (including the PAMP receptors, RIG-I and TLR3, as well as 2'5'OAS, PKR, TRIM25, RNF125, and NLRX1), and determine if their expression is altered by HCV infection...
  46. CARDIOVIRAL POLY (C) TRACTS AND VIRUS PATHOGENICITY
    Ann Palmenberg; Fiscal Year: 2000
    ..on their long poly(C)s to bind and inactivate sentinel cellular enzymes, such as dsRNA-activated protein kinase (PKR) in a manner analogous to adenovirus VAI RNAs...
  47. Alphavirus Minus Strand RNA Synthesis and RNase L
    DOROTHEA SAWICKI; Fiscal Year: 2009
    ..Thus, RNase L and nsP2 play role(s) in cessation and RC stability. Cessation was normal in PKR ko and wt MEF, eliminating roles for Mx1 and PKR. Four aims are proposed...
  48. EFFECT OF OPIOIDS ON 2-5OAS/PKR PATHWAY IN HIV INFECTION
    ROBERT SUHADOLNIK; Fiscal Year: 2002
    ..e., the 2', 5'-oligoadenylate synthetase (2-5OAS)/RNase L and p68 kinase (PKR) pathway...
  49. DYSREGULATED 2-5A SYNTHETASE/RNASE L/PKR PATHWAYS IN CFS
    ROBERT SUHADOLNIK; Fiscal Year: 1999
    ..investigator's laboratory has focused on the two dsRNA-dependent IFN- inducible 2'5'oligoA synthetase/RNase L and PKR pathways...
  50. TRANSLATIONAL CONTROL BY HEPATITIS C VIRUS
    Michael Gale; Fiscal Year: 2004
    ..are linked to disruption of cellular translational control and apoptotic programs through viral repression of the PKR protein kinase...
  51. REGULATION OF SMOOTH MUSCLE PROLIFERATION
    Rekha Patel; Fiscal Year: 2003
    ..b>PKR (protein kinase, RNA activated) is an IFN induced, growth inhibitory protein kinase, which is activated by double ..
  52. Autophagy: A Novel Antiviral Host Defense Pathway
    Beth Levine; Fiscal Year: 2007
    ..In addition, our recent data demonstrate that the well-characterized IFN-inducible antiviral molecule, PKR, is required for herpes simplex virus (HSV)-induced autophagy and that the HSV-l-encoded neurovirulence gene ..
  53. Autophagy:A Novel Antiviral Host Defense Pathway
    Beth Levine; Fiscal Year: 2002
    ..In addition, our preliminary data demonstrate that the well-characterized IFN-inducible antiviral molecule, PKR, is required for herpes simplex virus (HSV)-induced autophagy and that the HSV-1-encoded neurovirulence gene ..
  54. Regulation of Bcl2 Function Via Ceramide-Activated PP2A
    Peter Ruvolo; Fiscal Year: 2006
    ..Recently, we have found that ceramide can activate the double-stranded RNA dependent protein kinase (PKR). Interestingly, PKR can phosphorylate the B56 a regulatory B subunit of PP2A resulting in enhanced PP2A activity...
  55. Targeted Degradation of PKR mRNA with 2-5A Antisense
    Zan Xu; Fiscal Year: 2003
    ..b>PKR is emerging as an important mediator for inflammatory process by transducing signaling activation of NF-kappa B or ..
  56. PKR signaling in HIV-Associated Neurodegeneration
    Mehrdad Alirezaei; Fiscal Year: 2006
    ..b>PKR is an important pro-apoptotic kinase induced by TNF that triggers programmed cell death in a variety of cell types ..
  57. HSV US11 MEDIATED EVASION OF HOST SHUTOFF
    KEVIN CASSADY; Fiscal Year: 2001
    ..their pathogenic potential and evade an intracellular host defense system, the interferon induced protein kinase (PKR)...
  58. Function of ISG15 during Viral Infection
    DEBORAH LENSCHOW; Fiscal Year: 2006
    ..While several of these genes, such as PKR, RNaseL, and Mx have been studied, hundreds of these genes still have no known function...
  59. Hepatitis C Virus Proteins and Ethanol
    STEPHEN POLYAK; Fiscal Year: 2004
    ..abstract_text> ..
  60. Hepatitis C Virus Induced IL-8 & Inhibition of Interferon
    STEPHEN POLYAK; Fiscal Year: 2007
    ..Moreover, IL-8 or its receptors may prove to be suitable targets for therapeutic intervention in chronic hepatitis C. ..
  61. Proteomic Analysis of the Innate Antiviral Response
    Michael Katze; Fiscal Year: 2004
    ..abstract_text> ..
  62. Immunogenicity of Hepatitis C Virus (HCV) like particles
    Glen Barber; Fiscal Year: 2007
    ..abstract_text> ..
  63. Comparative Mouse Genomics Center
    Warren Ladiges; Fiscal Year: 2006
    ....
  64. The Role of CXCL9 in Genital HSV-2 Infection
    Daniel Carr; Fiscal Year: 2009
    ..g., vaccine or gene transfer) to reduce the incidence of infection or reduce the capacity of latent virus to reactivate. ..