Gene Symbol: Eif2s1
Description: eukaryotic translation initiation factor 2, subunit 1 alpha
Alias: 0910001O23Rik, 2410026C18Rik, 35kDa, Eif2a, eIF2alpha, eukaryotic translation initiation factor 2 subunit 1, eIF-2-alpha, eIF-2A, eIF-2alpha, eukaryotic translation initiation factor 2 subunit alpha, eukaryotic translation initiation factor 2A
Species: mouse
Products:     Eif2s1

Top Publications

  1. Carnevalli L, Pereira C, Jaqueta C, Alves V, Paiva V, Vattem K, et al. Phosphorylation of the alpha subunit of translation initiation factor-2 by PKR mediates protein synthesis inhibition in the mouse brain during status epilepticus. Biochem J. 2006;397:187-94 pubmed
    In response to different cellular stresses, a family of protein kinases phosphorylates eIF2alpha (alpha subunit of eukaryotic initiation factor-2), contributing to regulation of both general and genespecific translation proposed to ..
  2. Harding H, Zhang Y, Bertolotti A, Zeng H, Ron D. Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol Cell. 2000;5:897-904 pubmed
    ..This response is believed to be mediated by increased phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) and is hypothesized to reduce the work load imposed on the folding machinery during stress...
  3. Harding H, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M, et al. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol Cell. 2000;6:1099-108 pubmed
    Protein kinases that phosphorylate the alpha subunit of eukaryotic initiation factor 2 (eIF2alpha) are activated in stressed cells and negatively regulate protein synthesis...
  4. Jousse C, Oyadomari S, Novoa I, Lu P, Zhang Y, Harding H, et al. Inhibition of a constitutive translation initiation factor 2alpha phosphatase, CReP, promotes survival of stressed cells. J Cell Biol. 2003;163:767-75 pubmed
    Phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) on serine 51 is effected by specific stress-activated protein kinases...
  5. Scheuner D, Vander Mierde D, Song B, Flamez D, Creemers J, Tsukamoto K, et al. Control of mRNA translation preserves endoplasmic reticulum function in beta cells and maintains glucose homeostasis. Nat Med. 2005;11:757-64 pubmed
    ..Here we show that regulation of mRNA translation through phosphorylation of eukaryotic initiation factor 2 (eIF2alpha) is essential to preserve the integrity of the endoplasmic reticulum (ER) and to increase insulin production to ..
  6. McEwen E, Kedersha N, Song B, Scheuner D, Gilks N, Han A, et al. Heme-regulated inhibitor kinase-mediated phosphorylation of eukaryotic translation initiation factor 2 inhibits translation, induces stress granule formation, and mediates survival upon arsenite exposure. J Biol Chem. 2005;280:16925-33 pubmed
    ..The results demonstrated an essential role for HRI in mediating arsenite stress-induced phosphorylation of eukaryotic translation initiation factor 2alpha, inhibition of protein synthesis, stress granule formation, and survival. ..
  7. Back S, Scheuner D, Han J, Song B, Ribick M, Wang J, et al. Translation attenuation through eIF2alpha phosphorylation prevents oxidative stress and maintains the differentiated state in beta cells. Cell Metab. 2009;10:13-26 pubmed publisher
    ..through PERK-mediated phosphorylation of eukaryotic initiation factor 2 on Ser51 of the alpha subunit (eIF2alpha)...
  8. Liu Y, László C, Liu Y, Liu W, Chen X, Evans S, et al. Regulation of G(1) arrest and apoptosis in hypoxia by PERK and GCN2-mediated eIF2alpha phosphorylation. Neoplasia. 2010;12:61-8 pubmed
    ..protein kinase-like endoplasmic reticulum-related kinase (PERK) and phosphorylation of alpha subunit of eIF2 (eIF2alpha) confer cell adaptation to hypoxic stress...
  9. Cai Q, Brooks H. Phosphorylation of eIF2? via the general control kinase, GCN2, modulates the ability of renal medullary cells to survive high urea stress. Am J Physiol Renal Physiol. 2011;301:F1202-7 pubmed publisher
    ..Loss of GCN2 sensitized cells to urea stress, increasing the expression of activated caspase-3 and decreasing cell survival. Loss of GCN2 ablated urea-induced phosphorylation of eIF2? and reduced the expression of ATF3. ..

More Information


  1. Costa Mattioli M, Gobert D, Stern E, Gamache K, Colina R, Cuello C, et al. eIF2alpha phosphorylation bidirectionally regulates the switch from short- to long-term synaptic plasticity and memory. Cell. 2007;129:195-206 pubmed
    ..Phosphorylation of eIF2alpha inhibits general translation but selectively stimulates translation of ATF4, a repressor of CREB-mediated late-..
  2. Rutkowski D, Arnold S, Miller C, Wu J, Li J, Gunnison K, et al. Adaptation to ER stress is mediated by differential stabilities of pro-survival and pro-apoptotic mRNAs and proteins. PLoS Biol. 2006;4:e374 pubmed
    ..It underscores the contribution of posttranscriptional and posttranslational mechanisms in influencing this outcome. ..
  3. Hamanaka R, Bennett B, Cullinan S, Diehl J. PERK and GCN2 contribute to eIF2alpha phosphorylation and cell cycle arrest after activation of the unfolded protein response pathway. Mol Biol Cell. 2005;16:5493-501 pubmed
    ..ER) stress leads to activation of PKR-like ER kinase (PERK), eukaryotic translation initiation factor 2alpha (eIF2alpha) phosphorylation, repression of cyclin D1 translation, and subsequent cell cycle arrest in G1 phase...
  4. Jiang H, Wek R. Phosphorylation of the alpha-subunit of the eukaryotic initiation factor-2 (eIF2alpha) reduces protein synthesis and enhances apoptosis in response to proteasome inhibition. J Biol Chem. 2005;280:14189-202 pubmed
    ..Phosphorylation of eIF2alpha in mouse embryo fibroblast (MEF) cells subjected to proteasome inhibition leads to a significant reduction in ..
  5. Scheuner D, Song B, McEwen E, Liu C, Laybutt R, Gillespie P, et al. Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol Cell. 2001;7:1165-76 pubmed
    ..synthesis initiation through phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha) at Ser51...
  6. Wang X, Rao R, Kosakowska Cholody T, Masood M, Southon E, Zhang H, et al. Mitochondrial degeneration and not apoptosis is the primary cause of embryonic lethality in ceramide transfer protein mutant mice. J Cell Biol. 2009;184:143-58 pubmed publisher
    ..Thus, global compromise of ER and mitochondrial integrity caused by ceramide accumulation in CERT mutant mice primarily affects organogenesis rather than causing cell death via apoptotic pathways. ..
  7. Devi L, Ohno M. PERK mediates eIF2? phosphorylation responsible for BACE1 elevation, CREB dysfunction and neurodegeneration in a mouse model of Alzheimer's disease. Neurobiol Aging. 2014;35:2272-81 pubmed publisher
    ..Together, these findings suggest that PERK may be a disease-modifying therapeutic target to prevent multiple memory-disrupting mechanisms associated with AD. ..
  8. Pereira C, Sattlegger E, Jiang H, Longo B, Jaqueta C, Hinnebusch A, et al. IMPACT, a protein preferentially expressed in the mouse brain, binds GCN1 and inhibits GCN2 activation. J Biol Chem. 2005;280:28316-23 pubmed
    Translational control directed by the eukaryotic translation initiation factor 2 alpha-subunit (eIF2alpha) kinase GCN2 is important for coordinating gene expression programs in response to nutritional deprivation...
  9. Hao S, Sharp J, Ross Inta C, McDaniel B, Anthony T, Wek R, et al. Uncharged tRNA and sensing of amino acid deficiency in mammalian piriform cortex. Science. 2005;307:1776-8 pubmed
    ..Thus, a basic mechanism of nutritional stress management functions in mammalian brain to guide food selection for survival. ..
  10. Lewerenz J, Maher P. Basal levels of eIF2alpha phosphorylation determine cellular antioxidant status by regulating ATF4 and xCT expression. J Biol Chem. 2009;284:1106-15 pubmed publisher
    b>eIF2alpha is part of a multimeric complex that regulates cap-dependent translation...
  11. Timchenko N, Wang G, Timchenko L. RNA CUG-binding protein 1 increases translation of 20-kDa isoform of CCAAT/enhancer-binding protein beta by interacting with the alpha and beta subunits of eukaryotic initiation translation factor 2. J Biol Chem. 2005;280:20549-57 pubmed
    ..Our data demonstrate that the interaction of CUGBP1 with the eIF2alpha enhances the association of CUGBP1 with ribosomes and correlates with increased translation of LIP in the liver ..
  12. Gomez E, Powell M, Bevington A, Herbert T. A decrease in cellular energy status stimulates PERK-dependent eIF2alpha phosphorylation and regulates protein synthesis in pancreatic beta-cells. Biochem J. 2008;410:485-93 pubmed
    In the present study, we demonstrate that, in pancreatic beta-cells, eIF2alpha (eukaryotic initiation factor 2alpha) phosphorylation in response to a decrease in glucose concentration is primarily mediated by the activation of PERK [PKR (..
  13. Di Prisco G, Huang W, Buffington S, Hsu C, Bonnen P, Placzek A, et al. Translational control of mGluR-dependent long-term depression and object-place learning by eIF2?. Nat Neurosci. 2014;17:1073-82 pubmed publisher
    ..Our findings identify a new model of mGluR-LTD, which promises to be of value in the treatment of mGluR-LTD-linked cognitive disorders. ..
  14. Kimball S, Jefferson L. Induction of REDD1 gene expression in the liver in response to endoplasmic reticulum stress is mediated through a PERK, eIF2? phosphorylation, ATF4-dependent cascade. Biochem Biophys Res Commun. 2012;427:485-9 pubmed publisher
    ..Moreover, the induction of REDD1 gene expression was shown to require the protein kinase PERK and enhanced phosphorylation of its substrate, the ?-subunit of eukaryotic initiation factor 2. ..
  15. Lindahl M, Danilova T, Palm E, Lindholm P, Voikar V, Hakonen E, et al. MANF is indispensable for the proliferation and survival of pancreatic ? cells. Cell Rep. 2014;7:366-75 pubmed publisher
    ..We demonstrate that MANF specifically promotes ? cell proliferation and survival, thereby constituting a therapeutic candidate for ? cell protection and regeneration. ..
  16. Deng J, Lu P, Zhang Y, Scheuner D, Kaufman R, Sonenberg N, et al. Translational repression mediates activation of nuclear factor kappa B by phosphorylated translation initiation factor 2. Mol Cell Biol. 2004;24:10161-8 pubmed
    ..stressful conditions activate kinases that phosphorylate the alpha subunit of translation initiation factor 2 (eIF2alpha), thus attenuating mRNA translation and activating a gene expression program known as the integrated stress ..
  17. Chan S, Zhao X, Elfowiris A, Ratnam C, Herbert T. The role of de novo protein synthesis and SIRT1 in ER stress-induced Atf4 and Chop mRNA expression in mammalian cells. Biochimie. 2017;138:156-167 pubmed publisher
    ..This work highlights and extends previous findings, and provides important new insights into the mechanism of ER stress-induced expression of Atf4 and Chop mRNA that clearly warrants further investigation. ..
  18. Ravindran R, Loebbermann J, Nakaya H, Khan N, Ma H, Gama L, et al. The amino acid sensor GCN2 controls gut inflammation by inhibiting inflammasome activation. Nature. 2016;531:523-527 pubmed publisher
    ..Importantly, acute amino acid starvation suppressed intestinal inflammation via a mechanism dependent on GCN2. These results reveal a mechanism that couples amino acid sensing with control of intestinal inflammation via GCN2. ..
  19. Jiang H, Jiang L, Wek R. The eukaryotic initiation factor-2 kinase pathway facilitates differential GADD45a expression in response to environmental stress. J Biol Chem. 2007;282:3755-65 pubmed
    ..This study highlights the molecular mechanisms by which environmental stresses can differentially control central regulatory proteins targeted by the eIF2 kinase pathway. ..
  20. Dagon Y, Avraham Y, Berry E. AMPK activation regulates apoptosis, adipogenesis, and lipolysis by eIF2alpha in adipocytes. Biochem Biophys Res Commun. 2006;340:43-7 pubmed
    ..We have identified the alpha-subunit of the eukaryotic initiation factor-2 (eIF2alpha) as a target gene which is phosphorylated following AICAR treatment...
  21. Kimball S, Horetsky R, Ron D, Jefferson L, Harding H. Mammalian stress granules represent sites of accumulation of stalled translation initiation complexes. Am J Physiol Cell Physiol. 2003;284:C273-84 pubmed
    ..Finally, we also show that stress granules contain many, if not all, of the components of the 48S preinitiation complex, but not 60S ribosomal subunits, suggesting that they represent stalled translation initiation complexes. ..
  22. Verpooten D, Feng Z, Valyi Nagy T, Ma Y, Jin H, Yan Z, et al. Dephosphorylation of eIF2alpha mediated by the gamma134.5 protein of herpes simplex virus 1 facilitates viral neuroinvasion. J Virol. 2009;83:12626-30 pubmed publisher
    ..redirects protein phosphatase 1 to dephosphorylate the alpha subunit of translation initiation factor 2 (eIF2alpha). Additionally, it inhibits the induction of antiviral genes by TANK-binding kinase 1...
  23. 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
    ..As a first step in this direction, we show that a selective PKR inhibitor replicates the Pkr(-/-) phenotype in WT mice, enhancing long-term memory storage and L-LTP. ..
  24. Hirasawa H, Jiang C, Zhang P, Yang F, Yokota H. Mechanical stimulation suppresses phosphorylation of eIF2alpha and PERK-mediated responses to stress to the endoplasmic reticulum. FEBS Lett. 2010;584:745-52 pubmed publisher
    ..as stress to the endoplasmic reticulum induce an integrated stress response, which activates phosphorylation of eIF2alpha and leads to alleviation of cellular injury or apoptosis...
  25. Wu H, Wei L, Fan F, Ji S, Zhang S, Geng J, et al. Integration of Hippo signalling and the unfolded protein response to restrain liver overgrowth and tumorigenesis. Nat Commun. 2015;6:6239 pubmed publisher
    ..Thus, we conclude Yap integrates Hippo and UPR signalling to control liver size and tumorigenesis. ..
  26. Zeng N, Li Y, He L, Xu X, Galicia V, Deng C, et al. Adaptive basal phosphorylation of eIF2? is responsible for resistance to cellular stress-induced cell death in Pten-null hepatocytes. Mol Cancer Res. 2011;9:1708-17 pubmed publisher
    ..In summary, our study suggested a novel role of PTEN in regulating stress response through modulating the CReP/eIF2? pathway. ..
  27. Datta B, Majumdar A, Datta R, Balusu R. Treatment of cells with the angiogenic inhibitor fumagillin results in increased stability of eukaryotic initiation factor 2-associated glycoprotein, p67, and reduced phosphorylation of extracellular signal-regulated kinases. Biochemistry. 2004;43:14821-31 pubmed
    ..p67 protects eIF2alpha from phosphorylation by its kinases...
  28. Igarashi J, Sasaki T, Kobayashi N, Yoshioka S, Matsushita M, Shimizu T. Autophosphorylation of heme-regulated eukaryotic initiation factor 2? kinase and the role of the modification in catalysis. FEBS J. 2011;278:918-28 pubmed publisher
    ..Accordingly, we suggest that Tyr193, Thr485 and Thr490 are essential residues in the catalysis. ..
  29. Han J, Murthy R, Wood B, Song B, Wang S, Sun B, et al. ER stress signalling through eIF2? and CHOP, but not IRE1?, attenuates adipogenesis in mice. Diabetologia. 2013;56:911-24 pubmed publisher
    ..These results demonstrate that eIF2?-CHOP suppresses adipogenesis and limits expansion of fat mass in vivo in mice, rendering this pathway a potential therapeutic target. ..
  30. Disney J, Johnson K, Magnuson N, Sylvester S, Reeves R. High-mobility group protein HMG-I localizes to G/Q- and C-bands of human and mouse chromosomes. J Cell Biol. 1989;109:1975-82 pubmed
    ..To our knowledge, this is the first well-characterized mammalian protein that localizes primarily to G-band regions of chromosomes. ..
  31. Ito M, Yuan C, Okano H, Darnell R, Roeder R. Involvement of the TRAP220 component of the TRAP/SMCC coactivator complex in embryonic development and thyroid hormone action. Mol Cell. 2000;5:683-93 pubmed
    ..These results indicate that TRAP220 is essential for a wide range of physiological processes but also that it has gene- and activator-selective functions. ..
  32. Terenin I, Dmitriev S, Andreev D, Shatsky I. Eukaryotic translation initiation machinery can operate in a bacterial-like mode without eIF2. Nat Struct Mol Biol. 2008;15:836-41 pubmed publisher
    ..The switch from the conventional eukaryotic mode of translation initiation to the eIF2-independent mechanism occurs when eIF2 is inactivated by phosphorylation under stress conditions. ..
  33. Shang J, Gao N, Kaufman R, Ron D, Harding H, Lehrman M. Translation attenuation by PERK balances ER glycoprotein synthesis with lipid-linked oligosaccharide flux. J Cell Biol. 2007;176:605-16 pubmed
    ..In metazoans phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) on Ser(51) by PERK (PKR-like ER kinase), which is activated by ER stress, attenuates translation initiation...
  34. Harding H, Zhang Y, Scheuner D, Chen J, Kaufman R, Ron D. Ppp1r15 gene knockout reveals an essential role for translation initiation factor 2 alpha (eIF2alpha) dephosphorylation in mammalian development. Proc Natl Acad Sci U S A. 2009;106:1832-7 pubmed publisher
    ..loss-of-function phenotypes are rescued by a mutation, Eif2a(S51A), that prevents regulated phosphorylation of eIF2alpha. These findings reveal that the essential process of eIF2(alphaP) dephosphorylation is the predominant role of ..
  35. Connor J, Lyles D. Inhibition of host and viral translation during vesicular stomatitis virus infection. eIF2 is responsible for the inhibition of viral but not host translation. J Biol Chem. 2005;280:13512-9 pubmed
    ..In VSV-infected cells, the accumulation of phosphorylated (inactivated) eIF2alpha did not begin until well after host protein synthesis was inhibited, suggesting that it only plays a role in ..
  36. Devi L, Ohno M. Phospho-eIF2? level is important for determining abilities of BACE1 reduction to rescue cholinergic neurodegeneration and memory defects in 5XFAD mice. PLoS ONE. 2010;5:e12974 pubmed publisher
  37. Gardner L. Hypoxic inhibition of nonsense-mediated RNA decay regulates gene expression and the integrated stress response. Mol Cell Biol. 2008;28:3729-41 pubmed publisher
    ..and that this inhibition is dependent on phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2alpha)...
  38. Rajesh K, Krishnamoorthy J, Kazimierczak U, Tenkerian C, Papadakis A, Wang S, et al. Phosphorylation of the translation initiation factor eIF2α at serine 51 determines the cell fate decisions of Akt in response to oxidative stress. Cell Death Dis. 2015;6:e1591 pubmed publisher
    ..Hence, we propose that inactivation of eIF2αP may be a suitable approach to unleash the killing power of Akt in tumor cells treated with pro-oxidant drugs. ..
  39. 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
    ..These findings reveal that PKR can be an important inducer of cell death in response to chemotherapies through its ability to act independently of eIF2? phosphorylation. ..
  40. Guan B, Krokowski D, Majumder M, Schmotzer C, Kimball S, Merrick W, et al. Translational control during endoplasmic reticulum stress beyond phosphorylation of the translation initiation factor eIF2?. J Biol Chem. 2014;289:12593-611 pubmed publisher
    ..These studies advance our knowledge on the complexity of the communicating signaling pathways in controlling protein synthesis rates during chronic stress. ..
  41. Ma T, Trinh M, Wexler A, Bourbon C, Gatti E, Pierre P, et al. Suppression of eIF2? kinases alleviates Alzheimer's disease-related plasticity and memory deficits. Nat Neurosci. 2013;16:1299-305 pubmed publisher
  42. Bettaieb A, Matsuo K, Matsuo I, Wang S, Melhem R, Koromilas A, et al. Protein tyrosine phosphatase 1B deficiency potentiates PERK/eIF2? signaling in brown adipocytes. PLoS ONE. 2012;7:e34412 pubmed publisher
    ..Collectively, the data demonstrate that PTP1B is a physiologically-relevant modulator of ER stress in brown adipocytes and that PTP1B deficiency modulates PERK-eIF2? phosphorylation and protein synthesis. ..
  43. Paesler K, Xie K, Hettich M, Siwek M, Ryan D, Schröder S, et al. Limited effects of an eIF2αS51A allele on neurological impairments in the 5xFAD mouse model of Alzheimer's disease. Neural Plast. 2015;2015:825157 pubmed publisher
  44. Segev Y, Barrera I, Ounallah Saad H, Wibrand K, Sporild I, Livne A, et al. PKR Inhibition Rescues Memory Deficit and ATF4 Overexpression in ApoE ε4 Human Replacement Mice. J Neurosci. 2015;35:12986-93 pubmed publisher
    ..We think that these results propose a new mechanism by which ApoE4 affects brain function and suggest that inhibition of PKR is a way to restore memory impairment in early stages of sporadic AD. ..
  45. McInerney G, Kedersha N, Kaufman R, Anderson P, Liljestrom P. Importance of eIF2alpha phosphorylation and stress granule assembly in alphavirus translation regulation. Mol Biol Cell. 2005;16:3753-63 pubmed
    ..of the cellular stress response via phosphorylation of eukaryotic translation initiation factor 2alpha subunit (eIF2alpha)...
  46. Kouroku Y, Fujita E, Tanida I, Ueno T, Isoai A, Kumagai H, et al. ER stress (PERK/eIF2alpha phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation. Cell Death Differ. 2007;14:230-9 pubmed
    ..The eucaryotic translation initiation factor 2 alpha (eIF2alpha) A/A mutation, a knock-in to replace a phosphorylatable Ser51 with Ala51, and dominant-negative PERK inhibited ..
  47. Segev Y, Michaelson D, Rosenblum K. ApoE ?4 is associated with eIF2? phosphorylation and impaired learning in young mice. Neurobiol Aging. 2013;34:863-72 pubmed publisher
  48. Yamaji M, Tanaka T, Shigeta M, Chuma S, Saga Y, Saitou M. Functional reconstruction of NANOS3 expression in the germ cell lineage by a novel transgenic reporter reveals distinct subcellular localizations of NANOS3. Reproduction. 2010;139:381-93 pubmed publisher
    ..These findings unveil the presence of distinct posttranscriptional regulations in PGCs soon after their specification, for which RNA-binding proteins such as NANOS3 and TIAL1 would play critical functions. ..
  49. Yang L, Li S, Miao L, Huang H, Liang F, Teng X, et al. Rescue of Glaucomatous Neurodegeneration by Differentially Modulating Neuronal Endoplasmic Reticulum Stress Molecules. J Neurosci. 2016;36:5891-903 pubmed publisher
    ..Our results suggest that neuronal ER stress is a general mechanism of degeneration for both neuronal cell body and axon, and that therapeutic targeting of ER stress produces significant functional recovery. ..
  50. Mazor K, Stipanuk M. GCN2- and eIF2α-phosphorylation-independent, but ATF4-dependent, induction of CARE-containing genes in methionine-deficient cells. Amino Acids. 2016;48:2831-2842 pubmed
  51. Reineke L, Dougherty J, Pierre P, Lloyd R. Large G3BP-induced granules trigger eIF2? phosphorylation. Mol Biol Cell. 2012;23:3499-510 pubmed publisher
    ..Furthermore, these data suggest that stress granules are active in signaling to the translational machinery and may be important regulators of the innate immune response...
  52. DuRose J, Scheuner D, Kaufman R, Rothblum L, Niwa M. Phosphorylation of eukaryotic translation initiation factor 2alpha coordinates rRNA transcription and translation inhibition during endoplasmic reticulum stress. Mol Cell Biol. 2009;29:4295-307 pubmed publisher
    ..the well-characterized mTOR (mammalian target of rapamycin) pathway; instead, PERK-dependent phosphorylation of eIF2alpha plays a critical role in the inactivation of RRN3/TIF-IA...
  53. Smith J, Schmechel S, Raghavan A, Abelson M, Reilly C, Katze M, et al. Reovirus induces and benefits from an integrated cellular stress response. J Virol. 2006;80:2019-33 pubmed
    ..transcript and protein levels of P58(IPK), the cellular inhibitor of the eukaryotic initiation factor 2alpha (eIF2alpha) kinases PKR and PERK...
  54. Khoutorsky A, Sorge R, Prager Khoutorsky M, Pawlowski S, Longo G, Jafarnejad S, et al. eIF2? phosphorylation controls thermal nociception. Proc Natl Acad Sci U S A. 2016;113:11949-11954 pubmed
    ..Our results demonstrate that the cellular stress response pathway, mediated via p-eIF2?, represents a mechanism that could be used to alleviate pathological heat sensation. ..
  55. Mielke N, Schwarzer R, Calkhoven C, Kaufman R, Dorken B, Leutz A, et al. Eukaryotic initiation factor 2alpha phosphorylation is required for B-cell maturation and function in mice. Haematologica. 2011;96:1261-8 pubmed publisher
    ..The data suggest that regulation of translation through eIF2? phosphorylation is dispensable in hematopoietic reconstitution but essential during late B-cell development. ..
  56. Peidis P, Papadakis A, Rajesh K, Koromilas A. HDAC pharmacological inhibition promotes cell death through the eIF2? kinases PKR and GCN2. Aging (Albany NY). 2010;2:669-77 pubmed
    ..These results reveal a dual nature for eIF2? kinases with potential implications in the treatment with histone deacetylase inhibitors. ..
  57. Yoshimura F, Luo X, Zhao X, Gerard H, Hudson A. Up-regulation of a cellular protein at the translational level by a retrovirus. Proc Natl Acad Sci U S A. 2008;105:5543-8 pubmed publisher
    ..The ability of a simple retrovirus to regulate cellular gene expression at the translational level may be an important mechanism that contributes to pathogenesis. ..
  58. Gomez E, Powell M, Greenman I, Herbert T. Glucose-stimulated protein synthesis in pancreatic beta-cells parallels an increase in the availability of the translational ternary complex (eIF2-GTP.Met-tRNAi) and the dephosphorylation of eIF2 alpha. J Biol Chem. 2004;279:53937-46 pubmed
  59. So J, Cho S, Min S, Kimball S, Lee A. IRE1α-Dependent Decay of CReP/Ppp1r15b mRNA Increases Eukaryotic Initiation Factor 2α Phosphorylation and Suppresses Protein Synthesis. Mol Cell Biol. 2015;35:2761-70 pubmed publisher
    ..Taken together, the results of our study reveal a novel function of IRE1α in the regulation of eIF2α phosphorylation and the translational control. ..
  60. De Sousa P, Watson A, Schultz R. Transient expression of a translation initiation factor is conservatively associated with embryonic gene activation in murine and bovine embryos. Biol Reprod. 1998;59:969-77 pubmed
    ..Our results suggest that transient expression of eIF-1A in the mouse and cow is a conserved pattern of gene expression associated with EGA in mammals. ..
  61. Leitman J, Barak B, Benyair R, Shenkman M, Ashery U, Hartl F, et al. ER stress-induced eIF2-alpha phosphorylation underlies sensitivity of striatal neurons to pathogenic huntingtin. PLoS ONE. 2014;9:e90803 pubmed publisher
    ..A dephosphorylated state of eIF2? has been linked to cognition, which suggests that the effect of pathogenic huntingtin might also be a source of the early cognitive impairment seen in patients. ..
  62. Lee S, Kim Y. Phosphorylation of eIF2? attenuates statin-induced apoptosis by inhibiting the stabilization and translocation of p53 to the mitochondria. Int J Oncol. 2013;42:810-6 pubmed publisher
  63. 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 ..
  64. Chitnis N, Pytel D, Bobrovnikova Marjon E, Pant D, Zheng H, Maas N, et al. miR-211 is a prosurvival microRNA that regulates chop expression in a PERK-dependent manner. Mol Cell. 2012;48:353-64 pubmed publisher
    ..Our data suggest a model in which PERK-dependent miR-211 induction prevents premature chop accumulation and thereby provides a window of opportunity for the cell to re-establish homeostasis prior to apoptotic commitment. ..
  65. Backes S, Sperling K, Zwilling J, Gasteiger G, Ludwig H, Kremmer E, et al. Viral host-range factor C7 or K1 is essential for modified vaccinia virus Ankara late gene expression in human and murine cells, irrespective of their capacity to inhibit protein kinase R-mediated phosphorylation of eukaryotic translation initiation . J Gen Virol. 2010;91:470-82 pubmed publisher
    Vaccinia virus (VACV) infection induces phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha), which inhibits cellular and viral protein synthesis...
  66. Mahboubi H, Koromilas A, Stochaj U. AMP Kinase Activation Alters Oxidant-Induced Stress Granule Assembly by Modulating Cell Signaling and Microtubule Organization. Mol Pharmacol. 2016;90:460-8 pubmed publisher
    ..Taken together, we provide mechanistic insights into the regulation of SG formation. We propose that AMPK activation stimulates oxidant-induced SG formation but limits their fusion into larger granules. ..
  67. Sequeira S, Wen H, Avivar Valderas A, Farias E, Aguirre Ghiso J. Inhibition of eIF2alpha dephosphorylation inhibits ErbB2-induced deregulation of mammary acinar morphogenesis. BMC Cell Biol. 2009;10:64 pubmed publisher
    ..Phosphorylation of the translation initiation factor, eIF2alpha inhibits global protein synthesis and activates a stress signaling and growth suppressive program...
  68. Ohgaki R, Ohmori T, Hara S, Nakagomi S, Kanai Azuma M, Kaneda Nakashima K, et al. Essential Roles of L-Type Amino Acid Transporter 1 in Syncytiotrophoblast Development by Presenting Fusogenic 4F2hc. Mol Cell Biol. 2017;37: pubmed publisher
  69. Deng J, Harding H, Raught B, Gingras A, Berlanga J, Scheuner D, et al. Activation of GCN2 in UV-irradiated cells inhibits translation. Curr Biol. 2002;12:1279-86 pubmed
    ..that UV irradiation elicits phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha) by activating the kinase GCN2 in a manner that does not require SAPK/JNK or p38 MAP kinase...