Recombinant Mouse Interferon-induced, double-stranded RNA-activated protein kinase (Eif2ak2)

1. The mutant Rift Valley fever virus-C39S/C40S showed an attenuated phenotype in mice. The results show that two mechanisms are responsible for the attenuation; (1) loss of the interferon antagonistic propriety characteristic of the wild-type NSs and (2) the inability of the attenuated mutant to degrade Proteine Kinase R (PKR). PMID: 29530722
2. Pharmacological inhibition of the PKM2-EIF2AK2 pathway protects mice from lethal endotoxemia and polymicrobial sepsis. Conditional knockout of PKM2 in myeloid cells protects mice from septic death induced by NLRP3 and AIM2 inflammasome activation. PMID: 27779186
3. heme-regulated inhibitor (HRI), protein kinase R (PKR), PKR-like endoplasmic reticulum kinase, (PERK) and general control non-depressible 2 (GCN2) are sufficient for the integrated stress response; there are no additional eIF2alpha kinases in vertebrates PMID: 27633668
4. PKR inhibition ameliorated LPS-induced lung inflammation. PMID: 28511573
5. PKR activation is an essential part of the molecular switch from adaptation to inflammation in response to hyperosmotic stress. PMID: 27920257
6. We therefore concluded that in osteoblasts, P. gingivalis activated PKR, which in turn increased NLRP3 expression by activating NF-kappaB. Our results suggest that PKR modulates inflammation by regulating the expression of the NLRP3 inflammasome through the NF-kappaB pathway in periodontal diseases. PMID: 28341446
7. The data predicts that PKR diminishes inflammasome activity by controlling protein translation to repress the induction of factors that are critical for the activity of the cryopyrin inflammasome. PMID: 26794869
8. 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
9. Deletion of PKR does not affect HFD-induced obesity, hepatic steatosis or glucose metabolism, and only modestly affects adipose tissue inflammation. PMID: 26838266
10. 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
11. Data (including data from studies in transgenic/knockout mice) suggest that PACT/RAX (protein activator of protein kinase R) functions as negative regulator of PKR/Eif2ak2 (protein kinase R) in development of postnatal anterior pituitary tissue. PMID: 26414443
12. Data indicate increasing expression of PKR during TNF-a-induced osteoclast formation. Its inhibition prevents TNF-a-induced bone destruction in vivo and can be then considered as new therapeutic target for bone disease. PMID: 25739386
13. The authors show that Murine cytomegalovirus m142 and m143 knockout mutants attain organ titers equivalent to those attained by wild-type virus in Pkr knockout mice. PMID: 26512090
14. 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
15. Activated PKR inhibits pancreatic beta-cell proliferation through sumoylation-dependent stabilization of P53. PMID: 26446704
16. These data indicate that the association between PKR and TRBP integrates metabolism with translational control and inflammatory signaling and plays important roles in metabolic homeostasis and disease. PMID: 25843719
17. The age-associated accumulation of somatic mutations that occurs in the Nup98-HOXD13 (NHD13) mouse model of leukemia progression was significantly elevated by co-expression of a PKR transgene. PMID: 26202421
18. these findings demonstrate that PKR plays a major role in brain changes induced by LPS and could be a valid target to modulate neuroinflammation and Abeta production. PMID: 25687824
19. Thiamine deficiency activates the PKR-eIF2alpha pathway, increases the BACE1 expression levels of amyloid beta in specific thalamus nuclei and induces motor deficits and neurodegeneration. PMID: 25590804
20. These results suggest an unprecedented and unexpected model whereby snoRNAs play a role in the activation of PKR under metabolic stress. PMID: 25848059
21. PKR mediates angiogenesis through a VEGF pathway, which may form the basis for future intervention of Peripheral artery disease. PMID: 25587101
22. 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
23. The results demonstrate the ability of PKR to balance neuroinflammation by selectively modulating key cytokines and chemokines in CNS resident and CD4 T cells. PMID: 24642385
24. miR-29b mediated ethanol neurotoxicity through the SP1/RAX/PKR cascade. PMID: 24554719
25. PKR-induced translational inhibition appears to be specific to Dcp1a because the expression of other P-body components, Pan2, Pan3, Ccr4, or Caf1, did not result in the inhibition of poliovirus gene expression or induce eIF2alpha phosphorylation. PMID: 24382890
26. findings identified PKR as a mediator of anti-microbial activity and promoter of protection against disease caused by a non-viral pathogen, revealed that PKR is activated by CD40 via TRAF6 and TRAF2 PMID: 23990781
27. Local control of protein synthesis at synapses is crucial for synaptic plasticity, memory formation and learning processes. PMID: 23418065
28. PKR has important functions in the differentiation of chondrocytes. PMID: 23180319
29. Activation of double-stranded RNA-activated protein kinase (PKR) by interferon-stimulated gene 15 (ISG15) modification down-regulates protein translation PMID: 23229543
30. Data show that protein kinase R as the principal kinase that mediates eukaryotic initiation factor 2alpha (eIF2alpha) phosphorylation by large RasGAP SH3-binding protein (G3BP)-induced granules. PMID: 22833567
31. Report mechanism of autophagy control that involves STAT3 and PKR as interacting partners. PMID: 23084476
32. PKR may have a role in insulin sensitivity under normal physiological conditions and may represent a central mechanism for the integration of pathogen response and innate immunity with insulin action and metabolic pathways that are critical in obesity. PMID: 22948222
33. PKR positively regulates the differentiation of osteoblasts by mediating GSK-3beta activity through a beta-catenin-independent pathway. PMID: 22484461
34. Japanese encephalitis virus nonstructural protein 2A blocks double-stranded RNA-activated protein kinase PKR PMID: 22787234
35. 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
36. Heme-regulated eIF2alpha kinase activated Atf4 signaling pathway in oxidative stress and erythropoiesis. PMID: 22498744
37. The authors demonstrate for the first time that upon CD40 ligation, PKR is rapidly phosphorylated and activated, indicating that PKR is an early and novel downstream mediator of CD40 signaling pathways. PMID: 21994357
38. Loss of PKR increases the late phase of long-lasting synaptic potentiation (L-LTP) in hippocampal slices. These effects are caused by an IFN-gamma-mediated selective reduction in GABAergic synaptic action. PMID: 22153080
39. PKR is not activated by the West Nile virus dsRNA in infected cells. PMID: 21982595
40. Data show that PKR inhibition prevented Abeta42-induced activation of IkappaB and NF-kappaB, strongly decreased production and release of tumor necrosis factor (TNFalpha) and interleukin (IL)-1beta, and limited apoptosis. PMID: 21699726
41. sunitinib treatments prevent antiviral innate immune responses mediated by RNase L and PKR. PMID: 21636578
42. A critical role of PKR in regulating virus-host interaction. PMID: 21311764
43. In endotoxin tolerance, the kinetics of the differential ubiquitination of PKR is altered, resulting in a predominance of K48-linked chains, concomitant with a loss of PKR activation. PMID: 20978539
44. These findings reveal that activation of the antiviral response by rotavirus is dependent on MAVS/IPS-1 and IRF3 and involves both RIG-I and MDA-5 and that IFN-beta secretion during rotavirus infection is regulated by PKR. PMID: 21307186
45. Hyperoxia increases CHOP expression via an endoplasmic reticulum stress-independent, PKR-dependent pathway and that increased CHOP expression protects against hyperoxia-induced lung injury. PMID: 21186267
46. The eIF2alpha kinases PKR and GCN2 promote apoptosis. PMID: 21076179
47. Activation of the dsRNA-activated protein kinase PKR by viral RNA enabled phosphorylation of NFAR1 and NFAR2 on Thr 188 and Thr 315 PMID: 21123651
48. PKR plays important roles in the differentiation of osteoclasts. PMID: 20728438
49. These data suggest that PKR is a signaling molecule for immune responses during Respiratory syncytial virus infections. PMID: 20038207
50. Taken together, PKR and Hck were critical for DON-induced ribosomal recruitment of p38, its subsequent phosphorylation, and, ultimately, p38-driven proinflammatory cytokine expression. PMID: 20181660

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KEGG: mmu:19106

STRING: 10090.ENSMUSP00000024884

UniGene: Mm.378990