Ask about this productRelated genes to: EIF2AK1 antibody
- Gene:
- EIF2AK1 NIH gene
- Name:
- eukaryotic translation initiation factor 2 alpha kinase 1
- Previous symbol:
- -
- Synonyms:
- HRI, KIAA1369
- Chromosome:
- 7p22.1
- Locus Type:
- gene with protein product
- Date approved:
- 2005-01-19
- Date modifiied:
- 2016-10-05
- Gene:
- EIF2AK2 NIH gene
- Name:
- eukaryotic translation initiation factor 2 alpha kinase 2
- Previous symbol:
- PRKR
- Synonyms:
- PKR, EIF2AK1, PPP1R83
- Chromosome:
- 2p22.2
- Locus Type:
- gene with protein product
- Date approved:
- 1992-12-04
- Date modifiied:
- 2017-07-12
Related products to: EIF2AK1 antibody
Related articles to: EIF2AK1 antibody
- Cellular stressors inhibit general protein synthesis while upregulating stress response transcripts and/or proteins. Phosphorylation of the translation factor eIF2α by one of the several stress-activated kinases is a trigger for such signaling, known as the integrated stress response (ISR). The ISR regulates cell survival and function under stress. Here, germline knockout mice were used to determine contributions by three major ISR kinases, HRI/EIF2AK1, GCN2/EIF2AK4, and PKR//EIF2AK2, to pathogenesis of moderate contusive spinal cord injury (SCI) at the thoracic T9 level. One-day post-injury (dpi), reduced levels of peIF2α were found in Hri and Gcn2 , but not in Pkr mice. In addition, Hri mice showed attenuated expression of the downstream ISR transcripts, Atf4 or Chop. Such differential effects of SCI-activated ISR correlated with a strong or moderate enhancement of locomotor recovery in Hri or Gcn2 mice, respectively. Hri mice also showed reduced white matter loss, increased content of oligodendrocytes (OL) and attenuated neuroinflammation, including decreased lipid accumulation in microglia/macrophages. Cultured neonatal Hri OLs showed lower ISR cytotoxicity. Moreover, cell autonomous reduction in neuroinflammatory potential was observed in microglia and bone marrow-derived macrophages derived from Hri mice. These data identify HRI as a major positive regulator of SCI-associated secondary injury. In addition, targeting HRI may enable multimodal neuroprotection to enhance functional recovery after SCI. - Source: PubMed
Publication date: 2025/01/06
Saraswat Ohri SujataMyers Scott ARood BenjaminBrown Brandon LChilton Paula MSlomnicki LukaszLiu YuWei George ZAndres Kariena RMohan DivyaHoward Russell MWhittemore Scott RHetman Michal - Highly pathogenic avian influenza viruses (HPAIVs) is an extremely contagious and high mortality rates in chickens resulting in substantial economic impact on the poultry sector. Therefore, it is necessary to elucidate the pathogenic mechanism of HPAIV for infection control. - Source: PubMed
Vu Thi HaoHeo JubiHong YeojinKang SuyeonTran Ha Thi ThanhDang Hoang VuTruong Anh DucHong Yeong Ho - (IFN-I) are important inducers of the antiviral immune response and immune modulators. IFN-β is the most highly expressed IFN-I in the (CNS). The infection of SJL mice with the BeAn or the DA strain of (TMEV) results in a progressive demyelinating disease. C57BL/6 mice are usually resistant to TMEV-induced demyelination and eliminate these strains from the CNS within several weeks. Using C57BL/6 (IFN-β) mice infected with TMEV, we evaluated the role of IFN-β in neuroinfection. Despite the resistance of C57BL/6 (WT) mice to TMEV infection, DA-infected IFN-β mice had to be killed at 7 to 8 (dpi) due to severe clinical disease. In contrast, BeAn-infected IFN-β mice survived until 98 dpi. Nevertheless at 14 dpi, BeAn-infected IFN-β mice showed a stronger encephalitis and astrogliosis, higher viral load as well as higher mRNA levels of , (PKR), , , , and in the cerebrum than BeAn-infected WT mice. Moreover, the majority of IFN-β mice did not clear the virus from the CNS and developed mild demyelination in the spinal cord at 98 dpi, whereas virus and lesions were absent in the spinal cord of WT mice. Persistently infected IFN-β mice also had higher , , , , and mRNA levels in the spinal cord at 98 dpi than their virus-negative counterparts indicating an activation of IFN-I signaling and ongoing inflammation. Most importantly, BeAn-infected NesCre IFN-β mice, which do not express IFN-β in neurons, astrocytes and oligodendrocytes, only developed mild brain lesions similar to WT mice. Consequently, IFN-β produced by neuroectodermal cells does not seem to play a critical role in the resistance of C57BL/6 mice against fatal and demyelinating disease induced by TMEV strains. - Source: PubMed
Publication date: 2022/02/09
Bühler MelanieRunft SandraLi DandanGötting JasperDetje Claudia NNippold VanessaStoff MelanieBeineke AndreasSchulz ThomasKalinke UlrichBaumgärtner WolfgangGerhauser Ingo - EIF2AK1 and EIF2AK2 encode members of the eukaryotic translation initiation factor 2 alpha kinase (EIF2AK) family that inhibits protein synthesis in response to physiologic stress conditions. EIF2AK2 is also involved in innate immune response and the regulation of signal transduction, apoptosis, cell proliferation, and differentiation. Despite these findings, human disorders associated with deleterious variants in EIF2AK1 and EIF2AK2 have not been reported. Here, we describe the identification of nine unrelated individuals with heterozygous de novo missense variants in EIF2AK1 (1/9) or EIF2AK2 (8/9). Features seen in these nine individuals include white matter alterations (9/9), developmental delay (9/9), impaired language (9/9), cognitive impairment (8/9), ataxia (6/9), dysarthria in probands with verbal ability (6/9), hypotonia (7/9), hypertonia (6/9), and involuntary movements (3/9). Individuals with EIF2AK2 variants also exhibit neurological regression in the setting of febrile illness or infection. We use mammalian cell lines and proband-derived fibroblasts to further confirm the pathogenicity of variants in these genes and found reduced kinase activity. EIF2AKs phosphorylate eukaryotic translation initiation factor 2 subunit 1 (EIF2S1, also known as EIF2α), which then inhibits EIF2B activity. Deleterious variants in genes encoding EIF2B proteins cause childhood ataxia with central nervous system hypomyelination/vanishing white matter (CACH/VWM), a leukodystrophy characterized by neurologic regression in the setting of febrile illness and other stressors. Our findings indicate that EIF2AK2 missense variants cause a neurodevelopmental syndrome that may share phenotypic and pathogenic mechanisms with CACH/VWM. - Source: PubMed
Publication date: 2020/03/19
Mao DongxueReuter Chloe MRuzhnikov Maura R ZBeck Anita EFarrow Emily GEmrick Lisa TRosenfeld Jill AMackenzie Katherine MRobak LaurieWheeler Matthew TBurrage Lindsay CJain MahimLiu PengfeiCalame DanielKüry SébastienSillesen MartinSchmitz-Abe KlausTonduti DavideSpaccini LuiginaIascone MariaGenetti Casie AKoenig Mary KGraf MadelineTran AlyssaAlejandro Mercedes Lee Brendan HThiffault IsabelleAgrawal Pankaj BBernstein Jonathan ABellen Hugo JChao Hsiao-Tuan - A sustained activation of the unfolded protein response and the subsequent endoplasmic reticulum (ER) stress has been involved in the onset and severity of several metabolic diseases. The aim of this study was to analyze the association of DNA methylation signatures at ER stress genes with adiposity traits and related metabolic disorders. An epigenomic analysis within the Methyl Epigenome Network Association (MENA) project was conducted in an adult population (n=474). DNA methylation status in peripheral white blood cells was analyzed by a microarray approach. KEGG database was used to the characterization and discrimination of genes involved in the "protein processing in endoplasmic reticulum pathway". Anthropometric measurements and plasma metabolic profiles were analyzed. A total of 15 CpG sites at genes participating in ER pathway were strongly correlated with BMI after adjusted linear regression analyses (p<0.0001). These included cg08188400 (MAP2K7), cg20541779 (CASP12), cg24776411 (EIF2AK1), cg14190817 (HSPA5), cg21376454 (ERN1), cg06666486 (EIF2AK1), cg03211481 (DNAJC1), cg18357645 (OS9), cg05801879 (MBTPS1), cg20964082 (ERO1LB), cg17300868 (NFE2L2), cg03384128 (EIF2AK4), cg02712587 (EIF2AK4), cg04972384 (SELS), cg02240686 (EIF2AK2). Noteworthy, most of them were implicated in ER stress (p=2.9E-09). However, only methylation levels at cg20964082 (ERO1LB), cg17300868 (NFE2L2), cg05801879 (MBTPS1), and cg03384128 (EIF2AK4) also correlated with total fat mass. Interestingly, significant associations between methylation patterns at cg20964082 (ERO1LB) and cg17300868 (NFE2L2) and insulin and HOMA-IR index were found, whereas cg05801879 (MBTPS1) and cg03384128 (EIF2AK4) were correlated with triglyceride levels. This study suggests associations of methylation signatures at ER stress genes with adiposity and insulin resistance, as revealed by discriminative pathway analyses. - Source: PubMed
Publication date: 2017/11/28
Ramos-Lopez OmarRiezu-Boj Jose IMilagro Fermin IMartinez J Alfredo