| Function |
IFN-induced dsRNA-dependent serine/threonine-protein kinase which plays a key role in the innate immune response to viral infection and is also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation. Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1). Inhibits viral replication via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (EIF2S1), this phosphorylation impairs the recycling of EIF2S1 between successive rounds of initiation leading to inhibition of translation which eventually results in shutdown of cellular and viral protein synthesis. Also phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11. In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteosomal degradation. Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding proinflammatory cytokines and IFNs. Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6. Can act as both a positive and negative regulator of the insulin signaling pathway (ISP). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes. Can trigger apoptosis via FADD-mediated activation of CASP8. Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin. |
| Gene References into Functions |
- We demonstrated the activation of PKR pathway in CADASIL PMID: 30073405
- These results establish that PKR regulation through stress-induced TRBP phosphorylation is an important mechanism ensuring cellular recovery and preventing apoptosis due to sustained PKR activation. PMID: 29348664
- Auto-phosphorylation represses PKR activity. PMID: 28281686
- The finding that zebularine upregulates CYP gene expression through DNMT1 and PKR modulation sheds light on the mechanisms controlling hepatocyte function and thus may aid in the development of new in-vitro systems using high-functioning hepatocytes PMID: 28112215
- Multiples studies identified PKR as a crucial component of the host defense mechanism against viruses. The dynamic nature of PKR's structure allows it to interact with viral and many cellular molecules that ultimately affect the function of target molecules and downstream components of their pathways. [review] PMID: 29716441
- High PKR expression is associated with Colorectal Cancer Cell Invasiveness. PMID: 30275201
- The data demonstrate that E3 promotes F1 expression by blocking activation of the double-stranded RNA-activated protein kinase R (PKR). PMID: 29997208
- findings indicate that MSI1 plays a leading role in stress granule formation that grants cancer stem cell properties and chemoresistant stress granules in GBM, in response to stressful conditions via the PKR/eIF2alpha signalling cascade. PMID: 29486283
- Here, the authors report that LRP16 selectively interacts and activates double-stranded RNA-dependent kinase (PKR), and also acts as scaffolds to assist the formation of a ternary complex of PKR and IKKbeta, prolonging the polymers of ADP-ribose (PAR)-dependent nuclear factor kappa B (NF-kappaB) transactivation caused by DNA-damaging agents and confers acquired chemoresistance. PMID: 28820388
- These data suggest that even a modest increase in expression of this weak PKR antagonist is sufficient to enable RhCMV replication in human cells. PMID: 29263260
- Activation of PKR by TNF-alpha mRNA element enables PKR phosphorylation. PKR phosphorylation on Ser51 is necessary and sufficient for efficient splicing of TNF-alpha mRNA. PMID: 28683312
- PKR is co-opted by EV-A71 via viral protease 3C-mediated proteolytic activation to facilitate viral replication. PMID: 28702377
- Findings suggest a novel role for PKR in lung cancer cells as a mediator of radiation resistance possibly through translocation of the protein product to the nucleus. PMID: 27203671
- a novel, positive role for PKR activation and eIF2alpha phosphorylation in human globin mRNA splicing, is reported. PMID: 28374749
- Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated ablation of double-stranded RNA (dsRNA)-activated protein kinase R (PKR) restored p53 responses while boosting hepatitis C virus replication, showing that p53 inhibition results directly from viral activation of PKR. PMID: 28442604
- Gene silencing studies showed that the suppression of immunoproteasome induction is essentially dependent on protein kinase R (PKR). Indeed, the generation of a strictly immunoproteasome-dependent cytotoxic T lymphocyte epitope was impaired in in vitro processing experiments using isolated 20S proteasomes from HCV-infected cells and was restored by the silencing of PKR expression. PMID: 27833096
- data provide the first evidence that KSHV ORF57 plays a role in modulating PKR/eIF2alpha/SG axis and enhances virus production during virus lytic infection. PMID: 29084250
- The PKR is a key constituent of the metaflammasome and interacts directly with several inflammatory kinases, such as inhibitor kappaB (IkappaB) kinase (IKK) and c-Jun N-terminal kinase (JNK), insulin receptor substrate 1 (IRS1), and component of the translational machinery such as eIF2alpha. PMID: 26831644
- infection with New World arenaviruses JUNV and MACV, but not OW LASV, activated PKR, concomitant with elevated phosphorylation of the translation initiation factor alpha subunit of eukaryotic initiation factor 2 PMID: 28794024
- The stem-loop of noncoding RNA 886 is structural feature not only critical for inhibiting PKR autophosphorylation, but also the phosphorylation of its cellular substrate, EIF-2alpha. PMID: 28069888
- Protein kinase R (PKR) was required for induction of stress granules (SGs) by mumps virus (MuV) infection and regulated type III IFN (IFN-lambda1) mRNA stability. PMID: 27560627
- data establish a model in which the Influenza A virus NS1 N-terminal domain engages in a binding interaction to inhibit activation of PKR and ensure efficient viral propagation and virulence PMID: 28250123
- It was established in this report that interactions between PACT, ADAR1 and HIV-1-encoded Tat protein diminish the activation of PKR in response to HIV-1 infection. PMID: 28167698
- In insulitic islets from living patients with recent-onset T1D, most of the overexpressed ISGs, including GBP1, TLR3, OAS1, EIF2AK2, HLA-E, IFI6, and STAT1, showed higher expression in the islet core compared with the peri-islet area containing the surrounding immune cells PMID: 27422384
- NF90 exerts its antiviral activity by antagonizing the inhibitory role of NS1 on PKR phosphorylation PMID: 27423063
- Crucially, Chlamydia trachomatis infection resulted in robust IRE1alpha RNAse activity that was dependent on TLR4 signalling and inhibition of IRE1alpha RNAse activity prevented PKR activation. PMID: 27021640
- the expression of a Tat construct containing mutations in the basic region (49-57aa), which is responsible for the interaction with PKR, favored neither parasite growth nor IL-10 expression in infected macrophages. PMID: 26608746
- This study provides insight into the molecular pathology of Cornelia de Lange syndrome by establishing a relationship between NIPBL and HDAC8 mutations and PKR activation. PMID: 26725122
- The Newcastle disease virus-induced translation shutoff at late infection times was attributed to sustaining phosphorylation of eIF2a, which is mediated by continual activation of PKR and degradation of PP1. PMID: 26869028
- The sole essential function of cytomegalovirus TRS1 is to antagonize host PKR. PMID: 26716879
- results show that ceramide acts at two distinct levels of the insulin signaling pathway (IRS1 and Akt). PKR, which is induced by both inflammation signals and ceramide, could play a major role in the development of insulin resistance in muscle cells. PMID: 26698173
- Classical swine fever virus (CSFV) infection increased the phosphorylation of eukaryotic translation initiation factor (eIF)2alpha and its kinase PKR. The activation of PKR during CSFV infection is beneficial to the virus. PMID: 25899421
- these data indicate a pivotal role for PKR's protein-binding function on the proliferation of pancreatic beta cells through TRAF2/RIP1/NF-kappaB/c-Myc pathways. PMID: 25715336
- The results from this study indicate an important role of RAX/PKR association in regulating PKR activity as well as ethanol neurotoxicity PMID: 25592072
- The G3BP1-Caprin1-PKR complex represents a new mode of PKR activation and is important for antiviral activity of G3BP1 and PKR during infection with mengovirus. PMID: 25784705
- The data support a model in which activating RNAs induce formation of a back-to-back parallel PKR kinase dimer whereas nonactivating RNAs either fail to induce dimerization or produce an alternative, inactive dimer configuration. PMID: 26488609
- Tyrosine phosphorylated EIF2AK2 plays a role in the regulation of insulin induced protein synthesis and in maintaining insulin sensitivity. PMID: 26321373
- PKR expression correlates with inferior survival and shorter remission duration for acute myeloid leukemia patients. PMID: 26202421
- No significant association was determined between the rs2254958 EIF2AK2 polymorphism and the development of IBD, or clinical outcome. PMID: 25607115
- the affinity of PACT-PACT and PACT-PKR interactions is enhanced in dystonia patient lymphoblasts, thereby leading to intensified PKR activation and enhanced cellular death. PMID: 26231208
- Protein levels of PRKR were significantly increased in prefrontal cortex in chronic excessive alcohol use. PMID: 25704249
- Mechanism by which PK2 inhibits the model eIF2alpha kinase human RNA-dependent protein kinase (PKR) as well as native insect eIF2alpha kinases, is reported. PMID: 26216977
- G3BP1, G3BP2 and CAPRIN1 are required for translation of interferon stimulated mRNAs and are targeted by a dengue virus non-coding RNA. PMID: 24992036
- This study demonstrates that two interferon stimulated genes, i.e. PKR and ADAR1 have opposite effects on HTLV replication in vivo. PMID: 25389016
- PKR directly interacts with HIV-1 Tat and phosphorylates the first exon of Tat exclusively at five Ser/Thr residues, which inhibits Tat-mediated provirus transcription. PMID: 25653431
- Authors show that the PXXP domain within G3BP1 is essential for the recruitment of PKR to stress granules, for eIF2alpha phosphorylation driven by PKR, and for nucleating stress granules of normal composition. PMID: 25520508
- Further studies revealed that Andes virus nucleocapsid protein inhibited PKR dimerization, a critical step required for PKR autophosphorylation to attain activity. PMID: 25410857
- SUMO potentiates the inhibition of protein synthesis induced by PKR in response to dsRNA. PMID: 25074923
- Early dsRNA induced transient activation of the cellular dsRNA sensor protein kinase R (PKR), resulting in enhanced production of interferons and cytokines in cells and mice. PMID: 25297997
- Cyclophilin inhibitors reduce phosphorylation of PKR and eIF2alpha during HCV infection to allow for translation of ISG products. PMID: 24786893
- PKR is activated by dsRNA generated by Newcastle disease virus infection and inhibits Newcastle disease virus replication by eIF2alpha phosphorylation. PMID: 24684861
- This study identified 120 proteins present in active and inactive PKR nuclear complexes. PMID: 24347309
- In contrast to its previously described activity, PACT contributes to PKR dephosphorylation during HIV-1 replication. PMID: 24020926
- NF90 exerts antiviral activity through regulation of PKR phosphorylation and stress granules in infected cells. PMID: 24623135
- PKR is a maladaptive factor upregulated in hemodynamic overload that contributes to myocardial inflammation, cardiomyocyte apoptosis, and the development of congestive heart failure. PMID: 24463368
- PKR activation plays a major regulatory role in induction of apoptosis in response to ER stress and indicates the potential of PKR as possible target for neuroprotective therapeutics. PMID: 24334130
- Data suggest that M029 (an RNA-binding protein) plays pivotal role in determining cellular tropism of Myxoma virus in all mammalian cells tested; human protein kinase R/EIF2AK2 and RNA helicase A/DHX9 are two binding partners of M029. PMID: 23853588
- IFNA2 inhibits viral protein expression through PKR activation, leading to a decrease of viral protein synthesis. PMID: 24089560
- Low EIF2AK2 expression is associated with low response to therapy in endometrial cancer. PMID: 23682076
- STAT3 and EIF2AK2 interact and have roles in controlling fatty acid-induced autophagy PMID: 23221979
- RNA-dependent protein kinase is essential for 2-methoxyestradiol-induced autophagy in osteosarcoma cells. PMID: 23527187
- These results suggest that PKR and PKZ function by distinguishable mechanisms to modulate host responses including protein synthesis inhibition and stress granule formation. PMID: 23706307
- At the time of Alzheimer's disease diagnosis, a higher level of cerebrospinal fluid PKR can predict a faster rate of cognitive decline PMID: 23320095
- Low PKR and high EphA2 ratio is associated with non-small-cell lung cancer. PMID: 23370317
- PKR acts as a negative regulator of IFN induction triggered by DENVs and poly(IC), and this regulation relies on its dsRNA binding activity. PMID: 23372823
- PKR is crucial for the integrity of newly synthesized IFN mRNA, thereby generating an optimal host antiviral immune response. PMID: 23314571
- evidence that type 1 diabetes (DMT1) is response to viral infection: Data suggest that presence of immunoreactive enteroviral VP1 within pancreatic beta cells in DMT1 is associated with induction of PKR (and down-regulation of bcl-2-like protein 3). PMID: 23064357
- Authors conclude that host cells can employ PKR activation to restrict hepatitis C virus 1a replication through regulation of NF-kB expression. PMID: 23399035
- The results suggest that early in infection the herpes simplex virus 1 VHS RNase degrades RNAs that activate PKR. PMID: 23302873
- Activation of double-stranded RNA-activated protein kinase (PKR) by interferon-stimulated gene 15 (ISG15) modification down-regulates protein translation PMID: 23229543
- The substrate interacting residues in ck1alpha have been identified using the structural model of kinase - substrate peptide. The PKR interacting NS5A 1b residues have also been predicted. PMID: 23148689
- Suggest that PKR exerts a positive role in cell growth control of HCV-4 related hepatocellular carcinoma. PMID: 22894766
- Measles virus-induced stress granule formation was PKR dependent but impaired by ADAR1. PMID: 23115276
- PKR expression and the PKR binding domain of herpes simplex virus 1 Us11 are required for the antiautophagic activity of Us11. PMID: 23115300
- Report mechanism of autophagy control that involves STAT3 and PKR as interacting partners. PMID: 23084476
- The restriction of Bunyamwera virus replication mediated by interferon is an accumulated effect of at least three interferon-stimulated genes viperin, MTAP44 and PKR. PMID: 22896602
- an eIF-2alpha-dependent translation inhibition mechanism is sufficient to explain the PKR-mediated amplification of IPS-1-dependent IFN-beta induction by foreign RNA. PMID: 22948139
- Japanese encephalitis virus nonstructural protein 2A blocks double-stranded RNA-activated protein kinase PKR PMID: 22787234
- By binding to PKR with a comparable affinity, nc886 competes with dsRNA and attenuates PKR activation by dsRNA. PMID: 22986343
- 5'-triphosphate-containing, weakly structured RNAs activate PKR via interactions with both the dsRBD and a distinct triphosphate binding site that lacks 5'-nucleobase specificity. PMID: 22912486
- The PACT-PKR pathway represents a potential link between Abeta accumulation, PKR activation and tau phosphorylation. PMID: 21790829
- Data demonstrate that PACT-PACT interaction is essential for efficient PKR activation. PMID: 22473766
- results show a crucial role for PKR in inflammasome activation, and indicate that it should be possible to pharmacologically target this molecule to treat inflammation PMID: 22801494
- findings provide a new translational regulation of BACE1, under the control of double-stranded RNA dependant protein kinase in oxidative stress, where eIF2-alpha phosphorylation regulates PMID: 22306812
- The evaluation of CSF T-PKR and pPKR can discriminate between AD patients and NDC and could help to improve the biochemical diagnosis of AD. PMID: 22281122
- NF-kappa-B is involved in the protein activator of PKR-RNA-dependent protein kinase interaction and the production of pro-inflammatory cytokines in periodontitis. PMID: 21882225
- Cytomegalovirus TRS1 protein antagonize protein kinase R in a host-specific manner. PMID: 22278235
- This study used complementation of human cell lines stably deficient in PKR to probe the basis of PCR-mediated activation of MAPK and interferon beta induction by measles virus. PMID: 22381929
- Reduced PKR is associated with non-small cell lung cancer. PMID: 22102852
- PKR is involved in the innate immune effects mediated by HBx-siRNAs and further contributes to hepatitis B virus inhibition. PMID: 22174754
- Leishmania infection increased the expression of PKR and IFN-beta on induction of PKR-promoter activity. The observed effects required the engagement of TLR2. PMID: 21846836
- Specific inhibition of PKR at the peripheral level might decrease the inflammatory response in Alzheimer's disease. PMID: 21504114
- functions as a key mediator of IFN-alpha in opposing HBV replication PMID: 21710204
- Cellular localization studies showed that NP and Hsp40 co-localize primarily in the nucleus. During IAV infection in mammalian cells, expression of NP coincided with the dissociation of P58(IPK) from Hsp40 and decrease PKR phosphorylation PMID: 21698289
- The findings first indicate that PKR expression is an independent prognostic variable in non-small cell lung cancer patients. PMID: 20930042
- DRBP-120 is a double-stranded RNA (dsRNA)-binding protein, and it was detected in both the cytoplasm and the nucleus of HeLa cells associated with PKR. PMID: 16861808
- Mammalian orthoreovirus escape from host cell translational shutoff correlates with virus-induced cellular stress granules disruption and occurs in the presence of phosphorylated eIF2alpha in a PKR-independent manner. PMID: 21715487
- PKR activation led to selective apoptosis induction in K562 cells, which correlated with caspase-8 activity and enhanced expression of BAX. PMID: 21468538
- results demonstrate for the first time that stress-induced PACT phosphorylation functions to free PACT from the inhibitory interaction with TRBP and also to enhance its interaction with PKR PMID: 21526770
- These data demonstrate that the PKR- and NF-kappaB-dependent induction of pro-inflammatory molecules that accompanies reovirus-mediated killing. PMID: 21338484
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