Eif2ak2

Summary

Gene Symbol: Eif2ak2
Description: eukaryotic translation initiation factor 2-alpha kinase 2
Alias: 2310047A08Rik, 4732414G15Rik, AI467567, AI747578, Pkr, Prkr, Tik, interferon-induced, double-stranded RNA-activated protein kinase, IFN- type I-induced and dsRNA-activated kinase, IFN-induced and double-stranded RNA-activated kinase, P1/eIF-2A protein kinase, T-cell viral integration site, dsRNA-activated kinase, eIF-2 alpha, eIF-2A protein kinase 2, interferon-inducible RNA-dependent protein kinase, p68 kinase, protein kinase R, protein kinase RNA-activated, protein kinase, interferon-inducible double stranded RNA dependent, serine/threonine-protein kinase TIK, tyrosine-protein kinase EIF2AK2
Species: mouse
Products:     Eif2ak2

Top Publications

  1. Nakamura T, Furuhashi M, Li P, Cao H, Tuncman G, Sonenberg N, et al. Double-stranded RNA-dependent protein kinase links pathogen sensing with stress and metabolic homeostasis. Cell. 2010;140:338-48 pubmed publisher
    ..Here, we provide evidence that double-stranded RNA-dependent protein kinase (PKR) can respond to nutrient signals as well as endoplasmic reticulum (ER) stress and coordinate the activity of other ..
  2. Carr D, Wuest T, Tomanek L, Silverman R, Williams B. The lack of RNA-dependent protein kinase enhances susceptibility of mice to genital herpes simplex virus type 2 infection. Immunology. 2006;118:520-6 pubmed
    Mice deficient in RNA-dependent protein kinase (PKR-/-) or deficient in PKR and a functional 2',5'-oligoadenylate synthetase (OAS) pathway (PKR/RL-/-) are more susceptible to genital herpes simplex virus type 2 (HSV-2) infection than ..
  3. Talloczy Z, Jiang W, Virgin H, Leib D, Scheuner D, Kaufman R, et al. Regulation of starvation- and virus-induced autophagy by the eIF2alpha kinase signaling pathway. Proc Natl Acad Sci U S A. 2002;99:190-5 pubmed
    ..The mammalian IFN-inducible eIF2alpha kinase, PKR, rescues starvation-induced autophagy in GCN2-disrupted yeast, and pkr null and Ser-51 nonphosphorylatable mutant ..
  4. Shen S, Niso Santano M, Adjemian S, Takehara T, Malik S, Minoux H, et al. Cytoplasmic STAT3 represses autophagy by inhibiting PKR activity. Mol Cell. 2012;48:667-80 pubmed publisher
    ..domain of STAT3 was found to interact with the catalytic domain of the eIF2? kinase 2 EIF2AK2, best known as protein kinase R (PKR)...
  5. 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 ..
  6. 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...
  7. Cabanski M, Steinmüller M, Marsh L, Surdziel E, Seeger W, Lohmeyer J. PKR regulates TLR2/TLR4-dependent signaling in murine alveolar macrophages. Am J Respir Cell Mol Biol. 2008;38:26-31 pubmed
    The double-stranded RNA (dsRNA)-activated serine/threonine kinase R (PKR) is well characterized as an essential component of the innate antiviral response...
  8. Peidis P, Papadakis A, Muaddi H, Richard S, Koromilas A. Doxorubicin bypasses the cytoprotective effects of eIF2? phosphorylation and promotes PKR-mediated cell death. Cell Death Differ. 2011;18:145-54 pubmed publisher
    ..Different forms of DNA damage were shown to induce eIF2? phosphorylation by using PERK, GCN2 or PKR. However, the specificity of the eIF2? kinases and the biological role of eIF2? phosphorylation pathway in the DNA ..
  9. 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 ..
  10. Baltzis D, Li S, Koromilas A. Functional characterization of pkr gene products expressed in cells from mice with a targeted deletion of the N terminus or C terminus domain of PKR. J Biol Chem. 2002;277:38364-72 pubmed
    The interferon-inducible double-stranded RNA (dsRNA)-activated protein kinase, PKR, plays an important role in messenger (m) RNA translation by phosphorylating the alpha subunit of eukaryotic initiation factor 2...

Detail Information

Publications83

  1. Nakamura T, Furuhashi M, Li P, Cao H, Tuncman G, Sonenberg N, et al. Double-stranded RNA-dependent protein kinase links pathogen sensing with stress and metabolic homeostasis. Cell. 2010;140:338-48 pubmed publisher
    ..Here, we provide evidence that double-stranded RNA-dependent protein kinase (PKR) can respond to nutrient signals as well as endoplasmic reticulum (ER) stress and coordinate the activity of other ..
  2. Carr D, Wuest T, Tomanek L, Silverman R, Williams B. The lack of RNA-dependent protein kinase enhances susceptibility of mice to genital herpes simplex virus type 2 infection. Immunology. 2006;118:520-6 pubmed
    Mice deficient in RNA-dependent protein kinase (PKR-/-) or deficient in PKR and a functional 2',5'-oligoadenylate synthetase (OAS) pathway (PKR/RL-/-) are more susceptible to genital herpes simplex virus type 2 (HSV-2) infection than ..
  3. Talloczy Z, Jiang W, Virgin H, Leib D, Scheuner D, Kaufman R, et al. Regulation of starvation- and virus-induced autophagy by the eIF2alpha kinase signaling pathway. Proc Natl Acad Sci U S A. 2002;99:190-5 pubmed
    ..The mammalian IFN-inducible eIF2alpha kinase, PKR, rescues starvation-induced autophagy in GCN2-disrupted yeast, and pkr null and Ser-51 nonphosphorylatable mutant ..
  4. Shen S, Niso Santano M, Adjemian S, Takehara T, Malik S, Minoux H, et al. Cytoplasmic STAT3 represses autophagy by inhibiting PKR activity. Mol Cell. 2012;48:667-80 pubmed publisher
    ..domain of STAT3 was found to interact with the catalytic domain of the eIF2? kinase 2 EIF2AK2, best known as protein kinase R (PKR)...
  5. 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 ..
  6. 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...
  7. Cabanski M, Steinmüller M, Marsh L, Surdziel E, Seeger W, Lohmeyer J. PKR regulates TLR2/TLR4-dependent signaling in murine alveolar macrophages. Am J Respir Cell Mol Biol. 2008;38:26-31 pubmed
    The double-stranded RNA (dsRNA)-activated serine/threonine kinase R (PKR) is well characterized as an essential component of the innate antiviral response...
  8. Peidis P, Papadakis A, Muaddi H, Richard S, Koromilas A. Doxorubicin bypasses the cytoprotective effects of eIF2? phosphorylation and promotes PKR-mediated cell death. Cell Death Differ. 2011;18:145-54 pubmed publisher
    ..Different forms of DNA damage were shown to induce eIF2? phosphorylation by using PERK, GCN2 or PKR. However, the specificity of the eIF2? kinases and the biological role of eIF2? phosphorylation pathway in the DNA ..
  9. 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 ..
  10. Baltzis D, Li S, Koromilas A. Functional characterization of pkr gene products expressed in cells from mice with a targeted deletion of the N terminus or C terminus domain of PKR. J Biol Chem. 2002;277:38364-72 pubmed
    The interferon-inducible double-stranded RNA (dsRNA)-activated protein kinase, PKR, plays an important role in messenger (m) RNA translation by phosphorylating the alpha subunit of eukaryotic initiation factor 2...
  11. Dauber B, Martinez Sobrido L, Schneider J, Hai R, Waibler Z, Kalinke U, et al. Influenza B virus ribonucleoprotein is a potent activator of the antiviral kinase PKR. PLoS Pathog. 2009;5:e1000473 pubmed publisher
    Activation of the latent kinase PKR is a potent innate defense reaction of vertebrate cells towards viral infections, which is triggered by recognition of viral double-stranded (ds) RNA and results in a translational shutdown...
  12. Fishel R, Lescoe M, Rao M, Copeland N, Jenkins N, Garber J, et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993;75:1027-38 pubmed
    ..These data and reports indicating that S. cerevisiae msh2 mutations cause an instability of dinucleotide repeats like those associated with HNPCC suggest that hMSH2 is the HNPCC gene. ..
  13. Yang Y, Reis L, Pavlovic J, Aguzzi A, Schafer R, Kumar A, et al. Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase. EMBO J. 1995;14:6095-106 pubmed
    Double-stranded RNA-dependent protein kinase (PKR) has been implicated in interferon (IFN) induction, antiviral response and tumor suppression. We have generated mice devoid of functional PKR (Pkr%)...
  14. Kumar A, Yang Y, Flati V, Der S, Kadereit S, Deb A, et al. Deficient cytokine signaling in mouse embryo fibroblasts with a targeted deletion in the PKR gene: role of IRF-1 and NF-kappaB. EMBO J. 1997;16:406-16 pubmed
    The interferon (IFN)-induced double-stranded RNA (dsRNA)-activated Ser/Thr protein kinase (PKR) plays a role in the antiviral and antiproliferative effects of IFN...
  15. Lourenco M, Clarke J, Frozza R, Bomfim T, Forny Germano L, Batista A, et al. TNF-? mediates PKR-dependent memory impairment and brain IRS-1 inhibition induced by Alzheimer's ?-amyloid oligomers in mice and monkeys. Cell Metab. 2013;18:831-43 pubmed publisher
    ..dsRNA-dependent protein kinase (PKR) underlies peripheral insulin resistance in metabolic disorders...
  16. Balachandran S, Roberts P, Brown L, Truong H, Pattnaik A, Archer D, et al. Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection. Immunity. 2000;13:129-41 pubmed
    The double-stranded (ds) RNA-dependent protein kinase PKR is considered to play an important role in interferon's (IFN's) response to viral infection...
  17. Zhu P, Huang W, Kalikulov D, Yoo J, Placzek A, Stoica L, et al. Suppression of PKR promotes network excitability and enhanced cognition by interferon-?-mediated disinhibition. Cell. 2011;147:1384-96 pubmed publisher
    The double-stranded RNA-activated protein kinase (PKR) was originally identified as a sensor of virus infection, but its function in the brain remains unknown...
  18. Gorchakov R, Frolova E, Williams B, Rice C, Frolov I. PKR-dependent and -independent mechanisms are involved in translational shutoff during Sindbis virus infection. J Virol. 2004;78:8455-67 pubmed
    ..In this study, we used a combination of approaches, including the study of SIN replication in PKR(-/-) mouse embryo fibroblasts or in the presence of an excess of catalytically inactive PKR...
  19. 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...
  20. Min J, Li S, Sen G, Krug R. A site on the influenza A virus NS1 protein mediates both inhibition of PKR activation and temporal regulation of viral RNA synthesis. Virology. 2007;363:236-43 pubmed
    It is not known how influenza A viruses, important human pathogens, counter PKR activation, a crucial host antiviral response. Here we elucidate this mechanism...
  21. 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 ..
  22. Goh K, deVeer M, Williams B. The protein kinase PKR is required for p38 MAPK activation and the innate immune response to bacterial endotoxin. EMBO J. 2000;19:4292-7 pubmed
    Protein kinase RNA-regulated (PKR) is an established component of innate antiviral immunity. Recently, PKR has been shown to be essential for signal transduction in other situations of cellular stress...
  23. White C, Whitmore M, Williams B. Enlarged spleens without enlarged lymph nodes in tlr3-/- pkr-/- mice. J Interferon Cytokine Res. 2007;27:6-12 pubmed
    ..phenotypic studies in a mouse containing mutations in both toll-like receptor 3 (TLR3) and RNA-de-pendent protein kinase R (PKR) revealed comparable spleen and bone marrow cell populations in tlr3(-/)-, pkr(-/-), and tlr3(-/-)pkr(-/-..
  24. Wang X, Fan Z, Wang B, Luo J, Ke Z. Activation of double-stranded RNA-activated protein kinase by mild impairment of oxidative metabolism in neurons. J Neurochem. 2007;103:2380-90 pubmed
    ..The double-stranded RNA-activated protein kinase (PKR), has been well known for its anti-viral function...
  25. Thakur S, Zalinger Z, Johnson T, Imani F. Protein kinase R is a novel mediator of CD40 signaling and plays a critical role in modulating immunoglobulin expression during respiratory syncytial virus infection. Clin Vaccine Immunol. 2011;18:2060-6 pubmed publisher
    ..Previous studies in our laboratory have demonstrated that protein kinase R (PKR) plays a crucial role in IgE responses to double-stranded RNA (dsRNA) in vitro...
  26. Baltzis D, Pluquet O, Papadakis A, Kazemi S, Qu L, Koromilas A. The eIF2alpha kinases PERK and PKR activate glycogen synthase kinase 3 to promote the proteasomal degradation of p53. J Biol Chem. 2007;282:31675-87 pubmed
    ..This role is not specific for PERK, because the eIF2alpha kinase PKR also promotes p53 degradation in response to double-stranded RNA...
  27. Kazemi S, Mounir Z, Baltzis D, Raven J, Wang S, Krishnamoorthy J, et al. A novel function of eIF2alpha kinases as inducers of the phosphoinositide-3 kinase signaling pathway. Mol Biol Cell. 2007;18:3635-44 pubmed
    ..Herein, we show that a conditionally active form of the eIF2alpha kinase PKR acts upstream of PI3K and turns on the Akt/PKB-FRAP/mTOR pathway leading to S6 and 4E-BP1 phosphorylation...
  28. Nakayama Y, Plisch E, Sullivan J, Thomas C, Czuprynski C, Williams B, et al. Role of PKR and Type I IFNs in viral control during primary and secondary infection. PLoS Pathog. 2010;6:e1000966 pubmed publisher
    ..anti-viral signaling mechanisms of Type I IFNs is mediated by the IFN-inducible dsRNA activated protein kinase, PKR. Here, we have investigated the role of PKR and Type I IFNs in regulating viral clearance and CD8+ T cell response ..
  29. Hsu L, Park J, Zhang K, Luo J, Maeda S, Kaufman R, et al. The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature. 2004;428:341-5 pubmed
    ..of anti- and pro-apoptotic signalling events triggered by TLR4 identified the dsRNA responsive protein kinase PKR as a critical mediator of pathogen-induced macrophage apoptosis...
  30. Lu B, Nakamura T, Inouye K, Li J, Tang Y, Lundbäck P, et al. Novel role of PKR in inflammasome activation and HMGB1 release. Nature. 2012;488:670-4 pubmed publisher
    ..release mechanisms, here we identify a role for double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) in inflammasome activation. Exposure of macrophages to inflammasome agonists induced PKR autophosphorylation...
  31. Krishnamoorthy J, Mounir Z, Raven J, Koromilas A. The eIF2alpha kinases inhibit vesicular stomatitis virus replication independently of eIF2alpha phosphorylation. Cell Cycle. 2008;7:2346-51 pubmed
    ..Using mouse embryonic fibroblasts (MEFs) from knock-out mice we show that PKR and HRI have no effects on VSV replication as opposed to PERK and GCN2, which exhibit strong inhibitory effects...
  32. Chakrabarti A, Sadler A, Kar N, Young H, Silverman R, Williams B. Protein kinase R-dependent regulation of interleukin-10 in response to double-stranded RNA. J Biol Chem. 2008;283:25132-9 pubmed publisher
    The double-stranded RNA-activated protein kinase R (PKR) is an important component of antiviral defense...
  33. Kadereit S, Xu H, Engeman T, Yang Y, Fairchild R, Williams B. Negative regulation of CD8+ T cell function by the IFN-induced and double-stranded RNA-activated kinase PKR. J Immunol. 2000;165:6896-901 pubmed
    The IFN-induced and dsRNA-activated kinase (PKR) mediates the antiviral and antiproliferative effects of IFN-alpha and IFN-gamma. Despite these findings, PKR:(-/-) mice have no overt immunological phenotype...
  34. Abraham N, Stojdl D, Duncan P, Methot N, Ishii T, Dube M, et al. Characterization of transgenic mice with targeted disruption of the catalytic domain of the double-stranded RNA-dependent protein kinase, PKR. J Biol Chem. 1999;274:5953-62 pubmed
    The interferon-inducible, double-stranded RNA-dependent protein kinase PKR has been implicated in anti-viral, anti-tumor, and apoptotic responses...
  35. Couturier J, Morel M, Pontcharraud R, Gontier V, Fauconneau B, Paccalin M, et al. Interaction of double-stranded RNA-dependent protein kinase (PKR) with the death receptor signaling pathway in amyloid beta (Abeta)-treated cells and in APPSLPS1 knock-in mice. J Biol Chem. 2010;285:1272-82 pubmed publisher
    ..AD patients that translation is down-regulated by the activation of double-stranded RNA-dependent protein kinase (PKR)...
  36. Samuel C. The eIF-2 alpha protein kinases, regulators of translation in eukaryotes from yeasts to humans. J Biol Chem. 1993;268:7603-6 pubmed
  37. Khabar K, Siddiqui Y, Al Zoghaibi F, Al Haj L, Dhalla M, Zhou A, et al. RNase L mediates transient control of the interferon response through modulation of the double-stranded RNA-dependent protein kinase PKR. J Biol Chem. 2003;278:20124-32 pubmed
    ..of eukaryotic initiation factor 2alpha, eIF2alpha, by the double-stranded RNA-dependent protein kinase, PKR, constitutes a means of inhibiting viral replication...
  38. Zwaferink H, Stockinger S, Reipert S, Decker T. Stimulation of inducible nitric oxide synthase expression by beta interferon increases necrotic death of macrophages upon Listeria monocytogenes infection. Infect Immun. 2008;76:1649-56 pubmed publisher
    ..caspase activation or other interferon-inducible, death-associated proteins, including TRAIL, protein kinase R, and p53, were not necessary for cell death...
  39. von Roretz C, Gallouzi I. Protein kinase RNA/FADD/caspase-8 pathway mediates the proapoptotic activity of the RNA-binding protein human antigen R (HuR). J Biol Chem. 2010;285:16806-13 pubmed publisher
    ..Here, we show that this cleavage event is dependent on protein kinase RNA (PKR)...
  40. Elbahesh H, Scherbik S, Brinton M. West Nile virus infection does not induce PKR activation in rodent cells. Virology. 2011;421:51-60 pubmed publisher
    dsRNA-activated protein kinase (PKR) is activated by viral dsRNAs and phosphorylates eIF2a reducing translation of host and viral mRNA...
  41. Carpentier P, Williams B, Miller S. Distinct roles of protein kinase R and toll-like receptor 3 in the activation of astrocytes by viral stimuli. Glia. 2007;55:239-52 pubmed
    ..We found that the cytoplasmic dsRNA-activated kinase PKR is important for innate immune responses to TMEV infection, but has no role in their induction by poly I:C ..
  42. Qi Y, Zhang M, Li H, Frank J, Dai L, Liu H, et al. MicroRNA-29b regulates ethanol-induced neuronal apoptosis in the developing cerebellum through SP1/RAX/PKR cascade. J Biol Chem. 2014;289:10201-10 pubmed publisher
    ..Furthermore, our data indicated that miR-29b mediated ethanol neurotoxicity through the SP1/RAX/PKR cascade...
  43. 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 ..
  44. Couturier J, Paccalin M, Morel M, Terro F, Milin S, Pontcharraud R, et al. Prevention of the ?-amyloid peptide-induced inflammatory process by inhibition of double-stranded RNA-dependent protein kinase in primary murine mixed co-cultures. J Neuroinflammation. 2011;8:72 pubmed publisher
    ..In virus-infected cells, double-stranded RNA-dependent protein kinase (PKR) controls the NF-?B signaling pathway. It is well-known that PKR is activated in AD...
  45. Minor R, Limmon G, Miller DeGraff L, Dixon D, Andrews D, Kaufman R, et al. Double-stranded RNA-activated protein kinase regulates early innate immune responses during respiratory syncytial virus infection. J Interferon Cytokine Res. 2010;30:263-72 pubmed publisher
    ..The double-stranded RNA-activated protein kinase (PKR) functions to inhibit viral replication and participates in several signaling pathways associated with innate ..
  46. Oliver G, Wehr R, Jenkins N, Copeland N, Cheyette B, Hartenstein V, et al. Homeobox genes and connective tissue patterning. Development. 1995;121:693-705 pubmed
    ..Six 1 and Six 2 also are expressed in skeletal and smooth muscle, respectively. These genes may participate in the patterning of the distal tendons of the limb phalanges by setting positional values along the limb axes. ..
  47. Dorner M, Horwitz J, Donovan B, Labitt R, Budell W, Friling T, et al. Completion of the entire hepatitis C virus life cycle in genetically humanized mice. Nature. 2013;501:237-41 pubmed publisher
  48. Child S, Geballe A. Binding and relocalization of protein kinase R by murine cytomegalovirus. J Virol. 2009;83:1790-9 pubmed publisher
    Many viruses have evolved mechanisms to evade the repression of translation mediated by protein kinase R (PKR)...
  49. Cheng X, Byrne M, Brown K, Konopleva M, Kornblau S, Bennett R, et al. PKR inhibits the DNA damage response, and is associated with poor survival in AML and accelerated leukemia in NHD13 mice. Blood. 2015;126:1585-94 pubmed publisher
    Increased expression of the interferon-inducible double-stranded RNA-activated protein kinase (PKR) has been reported in acute leukemia and solid tumors, but the role of PKR has been unclear...
  50. Dagon Y, Dovrat S, Vilchik S, Hacohen D, Shlomo G, Sredni B, et al. Double-stranded RNA-dependent protein kinase, PKR, down-regulates CDC2/cyclin B1 and induces apoptosis in non-transformed but not in v-mos transformed cells. Oncogene. 2001;20:8045-56 pubmed
    The interferon (IFN)-induced, double stranded RNA (dsRNA)-activated serine/threonine kinase, PKR, is a potent negative regulator of cell growth when overexpressed in yeast or mammalian cells...
  51. Yoon C, Lee E, Lim D, Bae Y. PKR, a p53 target gene, plays a crucial role in the tumor-suppressor function of p53. Proc Natl Acad Sci U S A. 2009;106:7852-7 pubmed publisher
    Type I IFN-induced expression of dsRNA-activated protein kinase (PKR) during viral infection is a well-established antiviral mechanism...
  52. Singh M, Fowlkes V, Handy I, Patel C, Patel R. Essential role of PACT-mediated PKR activation in tunicamycin-induced apoptosis. J Mol Biol. 2009;385:457-68 pubmed publisher
    ..In this study, we examined the involvement of double-stranded RNA (dsRNA)-activated protein kinase (PKR) and its protein activator PACT in tunicamycin-induced apoptosis...
  53. Agranat L, Raitskin O, Sperling J, Sperling R. The editing enzyme ADAR1 and the mRNA surveillance protein hUpf1 interact in the cell nucleus. Proc Natl Acad Sci U S A. 2008;105:5028-33 pubmed publisher
    ..This study suggests a regulatory pathway by a combination of ADAR1 A-to-I editing enzyme and RNA degradation presumably with the aid of hUpf1...
  54. Pena J, Harris E. Dengue virus modulates the unfolded protein response in a time-dependent manner. J Biol Chem. 2011;286:14226-36 pubmed publisher
    ..These results demonstrate that time-dependent activation of the unfolded protein response by DENV-2 can override inhibition of translation, prevent apoptosis, and prolong the viral life cycle. ..
  55. Reineke L, Dougherty J, Pierre P, Lloyd R. Large G3BP-induced granules trigger eIF2? phosphorylation. Mol Biol Cell. 2012;23:3499-510 pubmed publisher
    ..embryonic fibroblasts depleted for individual eukaryotic initiation factor 2? (eIF2?) kinases, we identified protein kinase R as the principal kinase that mediates eIF2? phosphorylation by large G3BP-induced granules...
  56. Icely P, Gros P, Bergeron J, Devault A, Afar D, Bell J. TIK, a novel serine/threonine kinase, is recognized by antibodies directed against phosphotyrosine. J Biol Chem. 1991;266:16073-7 pubmed
    ..Among the remaining clones, we have characterized a cDNA encoding a novel kinase which we have designated TIK. Sequence analysis of this cDNA indicates that the TIK enzyme lacks the features thought to be conserved among ..
  57. Daher A, Laraki G, Singh M, Melendez Peña C, Bannwarth S, Peters A, et al. TRBP control of PACT-induced phosphorylation of protein kinase R is reversed by stress. Mol Cell Biol. 2009;29:254-65 pubmed publisher
    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...
  58. Gil M, Bohn E, O Guin A, Ramana C, Levine B, Stark G, et al. Biologic consequences of Stat1-independent IFN signaling. Proc Natl Acad Sci U S A. 2001;98:6680-5 pubmed
    ..Thus, the IFN receptors engage alternative Stat1-independent signaling pathways that have important physiological consequences. ..
  59. Honda K, Sakaguchi S, Nakajima C, Watanabe A, Yanai H, Matsumoto M, et al. Selective contribution of IFN-alpha/beta signaling to the maturation of dendritic cells induced by double-stranded RNA or viral infection. Proc Natl Acad Sci U S A. 2003;100:10872-7 pubmed
    ..the absence of either of the two target genes of IFN-alpha/beta, TLR3 and PKR (double-stranded-RNA-dependent protein kinase R), indicating the complexity of the IFN-alpha/beta-induced transcriptional program in DCs...
  60. Jiang H, Wek S, McGrath B, Lu D, Hai T, Harding H, et al. Activating transcription factor 3 is integral to the eukaryotic initiation factor 2 kinase stress response. Mol Cell Biol. 2004;24:1365-77 pubmed
  61. Austin B, James C, Silverman R, Carr D. Critical role for the oligoadenylate synthetase/RNase L pathway in response to IFN-beta during acute ocular herpes simplex virus type 1 infection. J Immunol. 2005;175:1100-6 pubmed
    ..However, protein kinase R mRNA was not up-regulated in the eye...
  62. Clavarino G, Cláudio N, Dalet A, Terawaki S, Couderc T, Chasson L, et al. Protein phosphatase 1 subunit Ppp1r15a/GADD34 regulates cytokine production in polyinosinic:polycytidylic acid-stimulated dendritic cells. Proc Natl Acad Sci U S A. 2012;109:3006-11 pubmed publisher
    ..GADD34, however, was shown to be required for normal cytokine production both in vitro and in vivo. These observations have important implications in linking further pathogen detection with the integrated stress response pathways. ..
  63. Feng G, Chong K, Kumar A, Williams B. Identification of double-stranded RNA-binding domains in the interferon-induced double-stranded RNA-activated p68 kinase. Proc Natl Acad Sci U S A. 1992;89:5447-51 pubmed
    The double-stranded RNA (dsRNA)-binding domain of the human p68 kinase has been localized to the N-terminal half of the enzyme by using progressive deletion analysis and in vitro binding assays...
  64. Yoshida K, Okamura H, Amorim B, Hinode D, Yoshida H, Haneji T. PKR-mediated degradation of STAT1 regulates osteoblast differentiation. Exp Cell Res. 2009;315:2105-14 pubmed publisher
    The double-stranded RNA-dependent protein kinase (PKR) plays a critical role in various biological responses including antiviral defense, cell differentiation, apoptosis, and tumorigenesis...
  65. Hirai K, Martinkova M, Igarashi J, Saiful I, Yamauchi S, El Mashtoly S, et al. Identification of Cys385 in the isolated kinase insertion domain of heme-regulated eIF2 alpha kinase (HRI) as the heme axial ligand by site-directed mutagenesis and spectral characterization. J Inorg Biochem. 2007;101:1172-9 pubmed
    ..Based on these spectroscopic findings, we conclude that Cys385 is an axial ligand of isolated KI. ..
  66. Goplen N, Gorska M, Stafford S, Rozario S, Guo L, Liang Q, et al. A phosphosite screen identifies autocrine TGF-beta-driven activation of protein kinase R as a survival-limiting factor for eosinophils. J Immunol. 2008;180:4256-64 pubmed
    ..The molecules that were differentially regulated include STATs and protein kinase R (PKR)...
  67. Wu S, Chang S, Wu H, Liao P, Chang M. Hepatitis C virus NS5A protein down-regulates the expression of spindle gene Aspm through PKR-p38 signaling pathway. J Biol Chem. 2008;283:29396-404 pubmed publisher
    ..effect was abolished when amino acid substitutions P2209L, T2214A, and T2217G known to interrupt the NS5A-PKR interaction were introduced into the NS5A protein...
  68. Pataer A, Vorburger S, Chada S, Balachandran S, Barber G, Roth J, et al. Melanoma differentiation-associated gene-7 protein physically associates with the double-stranded RNA-activated protein kinase PKR. Mol Ther. 2005;11:717-23 pubmed
    ..the melanoma differentiation-associated gene-7 (Ad-mda7; approved gene symbol IL24) leads to the rapid induction of PKR and activation of its downstream targets, resulting in apoptosis induction in human lung cancer cells...
  69. Taddeo B, Luo T, Zhang W, Roizman B. Activation of NF-kappaB in cells productively infected with HSV-1 depends on activated protein kinase R and plays no apparent role in blocking apoptosis. Proc Natl Acad Sci U S A. 2003;100:12408-13 pubmed
    ..In this report we show that activation of NF-kappaB in infected cells is linked to the activation of protein kinase R (PKR)...
  70. Teramachi J, Morimoto H, Baba R, Doi Y, Hirashima K, Haneji T. Double stranded RNA-dependent protein kinase is involved in osteoclast differentiation of RAW264.7 cells in vitro. Exp Cell Res. 2010;316:3254-62 pubmed publisher
    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...
  71. Yang M, May W, Ito T. JAZ requires the double-stranded RNA-binding zinc finger motifs for nuclear localization. J Biol Chem. 1999;274:27399-406 pubmed
    ..Thus, JAZ may belong to a class of zinc finger proteins that features dsRNA binding and may regulate cell growth via the unique dsRNA binding properties. ..
  72. Raveh T, Hovanessian A, Meurs E, Sonenberg N, Kimchi A. Double-stranded RNA-dependent protein kinase mediates c-Myc suppression induced by type I interferons. J Biol Chem. 1996;271:25479-84 pubmed
    ..We report in this work that interferon-induced double-stranded RNA-activated kinase (PKR) is one of the specific mediators of the antiproliferative effects of the cytokine...
  73. Dougherty J, Reineke L, Lloyd R. mRNA decapping enzyme 1a (Dcp1a)-induced translational arrest through protein kinase R (PKR) activation requires the N-terminal enabled vasodilator-stimulated protein homology 1 (EVH1) domain. J Biol Chem. 2014;289:3936-49 pubmed publisher
    ..Expression of wild-type or mutant GFP-Dcp1a induced phosphorylation of eIF2? through the eIF2? kinase protein kinase R (PKR). Activation of PKR required the amino-terminal EVH1 domain of Dcp1a...
  74. Pelsue S, Schweitzer P, Beamer W, Shultz L. Mapping of the flaky skin (fsn) mutation on distal mouse chromosome 17. Mamm Genome. 1995;6:758 pubmed
  75. Li Y, Xiao J, Tan Y, Wang J, Zhang Y, Deng X, et al. Inhibition of PKR ameliorates lipopolysaccharide-induced acute lung injury by suppressing NF-κB pathway in mice. Immunopharmacol Immunotoxicol. 2017;39:165-172 pubmed publisher
    ..Although protein kinase R (PKR) (double-stranded RNA-activated serine/threonine kinase) has been implicated in inflammatory response to ..
  76. Sen A, Pruijssers A, Dermody T, García Sastre A, Greenberg H. The early interferon response to rotavirus is regulated by PKR and depends on MAVS/IPS-1, RIG-I, MDA-5, and IRF3. J Virol. 2011;85:3717-32 pubmed publisher
    ..Interestingly, absence of the double-stranded RNA-dependent protein kinase PKR led to a profound defect in the capacity of host cells to secrete IFN-β in response to virus...
  77. Kang M, Lee C, Lee J, Dela Cruz C, Chen Z, Enelow R, et al. Cigarette smoke selectively enhances viral PAMP- and virus-induced pulmonary innate immune and remodeling responses in mice. J Clin Invest. 2008;118:2771-84 pubmed publisher
    ..induction of IL-12/IL-23 p40 and IFN-gamma, and the activation of double-stranded RNA-dependent protein kinase (PKR) and eukaryotic initiation factor-2alpha (eIF2alpha)...
  78. Okumura F, Okumura A, Uematsu K, Hatakeyama S, Zhang D, Kamura T. Activation of double-stranded RNA-activated protein kinase (PKR) by interferon-stimulated gene 15 (ISG15) modification down-regulates protein translation. J Biol Chem. 2013;288:2839-47 pubmed publisher
    ..However, how ISGylation contributes to innate immune responses is not clear. The dsRNA-dependent protein kinase (PKR) inhibits translation by phosphorylating eIF2? to exert its anti-viral effect...