Eif2ak3

Summary

Gene Symbol: Eif2ak3
Description: eukaryotic translation initiation factor 2 alpha kinase 3
Alias: Pek, Perk, eukaryotic translation initiation factor 2-alpha kinase 3, PRKR-like endoplasmic reticulum kinase, pancreatic eIF2-alpha kinase
Species: mouse
Products:     Eif2ak3

Top Publications

  1. Ghosh R, Lipson K, Sargent K, Mercurio A, Hunt J, Ron D, et al. Transcriptional regulation of VEGF-A by the unfolded protein response pathway. PLoS ONE. 2010;5:e9575 pubmed publisher
    ..IRE1alpha, PERK, and ATF6alpha, master regulators of the unfolded protein response (UPR), are activated under these conditions and ..
  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. Blais J, Filipenko V, Bi M, Harding H, Ron D, Koumenis C, et al. Activating transcription factor 4 is translationally regulated by hypoxic stress. Mol Cell Biol. 2004;24:7469-82 pubmed
    ..by eukaryotic initiation factor 2alpha (eIF2alpha) phosphorylation by the endoplasmic reticulum (ER) kinase PERK. Here we show through microarray analysis of polysome-bound RNA in aerobic and hypoxic HeLa cells that a subset of ..
  4. 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
    Exposure of cells to endoplasmic reticulum (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 ..
  5. Wang R, McGrath B, Kopp R, Roe M, Tang X, Chen G, et al. Insulin secretion and Ca2+ dynamics in ?-cells are regulated by PERK (EIF2AK3) in concert with calcineurin. J Biol Chem. 2013;288:33824-36 pubmed publisher
    Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) (EIF2AK3) is essential for normal development and function of the insulin-secreting ?-cell...
  6. Brewer J, Diehl J. PERK mediates cell-cycle exit during the mammalian unfolded protein response. Proc Natl Acad Sci U S A. 2000;97:12625-30 pubmed
    ..Three ER transmembrane protein kinases (Ire1alpha, Ire1beta, and PERK) have been implicated as proximal effectors of the mammalian UPR...
  7. Lin Y, Huang G, Jamison S, Li J, Harding H, Ron D, et al. PERK activation preserves the viability and function of remyelinating oligodendrocytes in immune-mediated demyelinating diseases. Am J Pathol. 2014;184:507-19 pubmed publisher
    ..Activation of pancreatic endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic reticulum stress modulates cell viability and function under stressful ..
  8. Harding H, Zeng H, Zhang Y, Jungries R, Chung P, Plesken H, et al. Diabetes mellitus and exocrine pancreatic dysfunction in perk-/- mice reveals a role for translational control in secretory cell survival. Mol Cell. 2001;7:1153-63 pubmed
    The protein kinase PERK couples protein folding in the endoplasmic reticulum (ER) to polypeptide biosynthesis by phosphorylating the alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha), attenuating translation ..
  9. Zhang P, McGrath B, Li S, Frank A, Zambito F, Reinert J, et al. The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas. Mol Cell Biol. 2002;22:3864-74 pubmed
    ..Among the four eIF-2 alpha kinases present in mammals, PERK is most highly expressed in the pancreas, suggesting that it may be responsible for the high eIF-2 alpha[P] levels ..

More Information

Publications70

  1. Liu L, Wise D, Diehl J, Simon M. Hypoxic reactive oxygen species regulate the integrated stress response and cell survival. J Biol Chem. 2008;283:31153-62 pubmed publisher
    ..mRNA translation by modulating the mammalian target of rapamycin (mTOR) and pancreatic eIF2alpha kinase (PERK) pathways...
  2. Gupta S, McGrath B, Cavener D. PERK (EIF2AK3) regulates proinsulin trafficking and quality control in the secretory pathway. Diabetes. 2010;59:1937-47 pubmed publisher
    Loss-of-function mutations in Perk (EIF2AK3) result in permanent neonatal diabetes in humans (Wolcott-Rallison Syndrome) and mice...
  3. Harding H, Zhang Y, Zeng H, Novoa I, Lu P, Calfon M, et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell. 2003;11:619-33 pubmed
    ..b>Perk(-/-) cells, lacking an upstream ER stress-activated eIF2alpha kinase that activates Atf4, accumulate endogenous ..
  4. 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
    ..Here, we demonstrate that the endoplasmic reticulum-resident eIF2alpha kinase PERK mediates the proteasomal degradation of p53 independently of translational control...
  5. Iwawaki T, Akai R, Yamanaka S, Kohno K. Function of IRE1 alpha in the placenta is essential for placental development and embryonic viability. Proc Natl Acad Sci U S A. 2009;106:16657-62 pubmed publisher
    ..These findings reveal that IRE1alpha plays an essential function in extraembryonic tissues and highlight the relationship of physiological ER stress and angiogenesis in the placenta during pregnancy in mammals. ..
  6. Delepine M, Nicolino M, Barrett T, Golamaully M, Lathrop G, Julier C. EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. Nat Genet. 2000;25:406-9 pubmed
    ..The gene encoding the eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) resides in this interval; thus we explored it as a candidate...
  7. 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
    ..Genetic deletion of eIF2? kinase PERK prevented enhanced phosphorylation of eIF2? and deficits in protein synthesis, synaptic plasticity and spatial ..
  8. Feng D, Wei J, Gupta S, McGrath B, Cavener D. Acute ablation of PERK results in ER dysfunctions followed by reduced insulin secretion and cell proliferation. BMC Cell Biol. 2009;10:61 pubmed publisher
    A deficiency in Perk (EIF2AK3) causes multiple neonatal defects in humans known as the Wolcott Rallison syndrome. Perk KO mice exhibit the same array of defects including permanent neonatal diabetes (PND)...
  9. Cullinan S, Zhang D, Hannink M, Arvisais E, Kaufman R, Diehl J. Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival. Mol Cell Biol. 2003;23:7198-209 pubmed
    Activation of PERK following the accumulation of unfolded proteins in the endoplasmic reticulum (ER) promotes translation inhibition and cell cycle arrest...
  10. Bobrovnikova Marjon E, Hatzivassiliou G, Grigoriadou C, Romero M, Cavener D, Thompson C, et al. PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation. Proc Natl Acad Sci U S A. 2008;105:16314-9 pubmed publisher
    The role of the endoplasmic reticulum stress-regulated kinase, PERK, in mammary gland function was assessed through generation of a targeted deletion in mammary epithelium...
  11. 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
    ..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...
  12. Fernandez J, Bode B, Koromilas A, Diehl J, Krukovets I, Snider M, et al. Translation mediated by the internal ribosome entry site of the cat-1 mRNA is regulated by glucose availability in a PERK kinase-dependent manner. J Biol Chem. 2002;277:11780-7 pubmed
    ..in a manner dependent upon phosphorylation of eukaryotic initiation factor 2alpha by the transmembrane ER kinase, PERK. Because PERK is a key constituent of the UPR, it is concluded that induction of cat-1 gene expression is part of ..
  13. Kumar R, Azam S, Sullivan J, Owen C, Cavener D, Zhang P, et al. Brain ischemia and reperfusion activates the eukaryotic initiation factor 2alpha kinase, PERK. J Neurochem. 2001;77:1418-21 pubmed
    ..in all reperfused groups, the RNA-dependent protein kinase (PKR)-like endoplasmic reticulum eIF2alpha kinase (PERK) exhibited an isoform mobility shift on SDS-PAGE, consistent with the activation of the kinase...
  14. Cullinan S, Diehl J. PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell survival following endoplasmic reticulum stress. J Biol Chem. 2004;279:20108-17 pubmed
    ..b>PERK-dependent activation of NF-E2-related factor-2 (Nrf2) is critical for survival signaling during this response; ..
  15. Wu J, Rutkowski D, Dubois M, Swathirajan J, Saunders T, Wang J, et al. ATF6alpha optimizes long-term endoplasmic reticulum function to protect cells from chronic stress. Dev Cell. 2007;13:351-64 pubmed
    In vertebrates, three proteins--PERK, IRE1alpha, and ATF6alpha--sense protein-misfolding stress in the ER and initiate ER-to-nucleus signaling cascades to improve cellular function...
  16. Iida K, Li Y, McGrath B, Frank A, Cavener D. PERK eIF2 alpha kinase is required to regulate the viability of the exocrine pancreas in mice. BMC Cell Biol. 2007;8:38 pubmed
    Deficiency of the PERK eIF2 alpha kinase in humans and mice results in postnatal exocrine pancreatic atrophy as well as severe growth and metabolic anomalies in other organs and tissues...
  17. Marciniak S, Garcia Bonilla L, Hu J, Harding H, Ron D. Activation-dependent substrate recruitment by the eukaryotic translation initiation factor 2 kinase PERK. J Cell Biol. 2006;172:201-9 pubmed
    ..translation initiation factor 2 (eIF2alpha) by the endoplasmic reticulum (ER) stress-activated protein kinase PERK modulates protein synthesis and couples the production of ER client proteins with the organelle's capacity to fold ..
  18. Harding H, Zhang Y, Ron D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature. 1999;397:271-4 pubmed
    ..Here we describe the cloning of perk, a gene encoding a type I transmembrane ER-resident protein...
  19. Bertolotti A, Zhang Y, Hendershot L, Harding H, Ron D. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol. 2000;2:326-32 pubmed
    b>PERK and IRE1 are type-I transmembrane protein kinases that reside in the endoplasmic reticulum (ER) and transmit stress signals in response to perturbation of protein folding...
  20. Wei J, Sheng X, Feng D, McGrath B, Cavener D. PERK is essential for neonatal skeletal development to regulate osteoblast proliferation and differentiation. J Cell Physiol. 2008;217:693-707 pubmed publisher
    Loss of function mutations of Perk (eukaryotic translation initiation factor 2 alpha kinase 3) in humans and mice cause severe neonatal developmental defects, including diabetes, growth retardation and multiple skeletal dysplasias...
  21. Hamanaka R, Bobrovnikova Marjon E, Ji X, Liebhaber S, Diehl J. PERK-dependent regulation of IAP translation during ER stress. Oncogene. 2009;28:910-20 pubmed publisher
    ..One of the proximal effectors of the ER stress response, the PKR-like ER kinase (PERK), leads to cellular adaptation to stress by multiple mechanisms, including attenuation of protein synthesis and ..
  22. Huang G, Yao J, Zeng W, Mizuno Y, Kamm K, Stull J, et al. ER stress disrupts Ca2+-signaling complexes and Ca2+ regulation in secretory and muscle cells from PERK-knockout mice. J Cell Sci. 2006;119:153-61 pubmed
    ..against ER stress by activation of the unfolded protein response (UPR) that is regulated by the protein kinase PERK, which phosphorylates the translation initiation factor 2 eIF2alpha to attenuate protein synthesis...
  23. Liang S, Zhang W, McGrath B, Zhang P, Cavener D. PERK (eIF2alpha kinase) is required to activate the stress-activated MAPKs and induce the expression of immediate-early genes upon disruption of ER calcium homoeostasis. Biochem J. 2006;393:201-9 pubmed
    The eIF2alpha (eukaryotic initiation factor-2alpha) kinase PERK (doublestranded RNA-activated protein kinase-like ER kinase) is essential for the normal function of highly secretory cells in the pancreas and skeletal system, as well as ..
  24. Pavio N, Romano P, Graczyk T, Feinstone S, Taylor D. Protein synthesis and endoplasmic reticulum stress can be modulated by the hepatitis C virus envelope protein E2 through the eukaryotic initiation factor 2alpha kinase PERK. J Virol. 2003;77:3578-85 pubmed
    ..Here we show that the PKR-like ER-resident kinase (PERK) binds to and is also inhibited by E2...
  25. Yan W, Frank C, Korth M, Sopher B, Novoa I, Ron D, et al. Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK. Proc Natl Acad Sci U S A. 2002;99:15920-5 pubmed
    ..P58(IPK) interacts with and inhibits the PKR-like ER-localized eIF2alpha kinase PERK, which is normally activated during the ER-stress response to protect cells from ER stress by attenuating protein ..
  26. Gupta S, McGrath B, Cavener D. PERK regulates the proliferation and development of insulin-secreting beta-cell tumors in the endocrine pancreas of mice. PLoS ONE. 2009;4:e8008 pubmed publisher
    b>PERK eIF2alpha kinase is required for the proliferation of the insulin-secreting beta- cells as well as insulin synthesis and secretion...
  27. Zhou J, Liu C, Back S, Clark R, Peisach D, Xu Z, et al. The crystal structure of human IRE1 luminal domain reveals a conserved dimerization interface required for activation of the unfolded protein response. Proc Natl Acad Sci U S A. 2006;103:14343-8 pubmed
    ..Inositol-requiring kinase 1 (IRE1) and PKR-related ER kinase (PERK) are two type I transmembrane ER-localized protein kinase receptors that signal the UPR through a process that ..
  28. Yamaguchi Y, Larkin D, Lara Lemus R, Ramos Castaneda J, Liu M, Arvan P. Endoplasmic reticulum (ER) chaperone regulation and survival of cells compensating for deficiency in the ER stress response kinase, PERK. J Biol Chem. 2008;283:17020-9 pubmed publisher
    The activity of PERK, an endoplasmic reticulum (ER) transmembrane protein kinase, assists in an ER stress response designed to inhibit general protein synthesis while allowing upregulated synthesis of selective proteins such as the ATF4 ..
  29. 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...
  30. Lin W, Harding H, Ron D, Popko B. Endoplasmic reticulum stress modulates the response of myelinating oligodendrocytes to the immune cytokine interferon-gamma. J Cell Biol. 2005;169:603-12 pubmed
    ..expression of IFN-gamma in mice that were heterozygous for a loss of function mutation in pancreatic ER kinase (PERK) dramatically reduced animal survival, promoted CNS hypomyelination, and enhanced oligodendrocyte loss...
  31. Li Y, Iida K, O Neil J, Zhang P, Li S, Frank A, et al. PERK eIF2alpha kinase regulates neonatal growth by controlling the expression of circulating insulin-like growth factor-I derived from the liver. Endocrinology. 2003;144:3505-13 pubmed
    Humans afflicted with the Wolcott-Rallison syndrome and mice deficient for PERK (pancreatic endoplasmic reticulum eIF2alpha kinase) show severe postnatal growth retardation...
  32. Mann M, Pereira E, Liao N, Hendershot L. UPR-induced resistance to etoposide is downstream of PERK and independent of changes in topoisomerase II? levels. PLoS ONE. 2012;7:e47931 pubmed publisher
    ..Conversely, PERK activation did not contribute to changes in Topo II? protein levels, but it did play a significant role in the UPR-..
  33. Wang Y, Alam G, Ning Y, Visioli F, Dong Z, Nor J, et al. The unfolded protein response induces the angiogenic switch in human tumor cells through the PERK/ATF4 pathway. Cancer Res. 2012;72:5396-406 pubmed publisher
    ..In vitro studies revealed that partially blocking UPR signaling by silencing protein kinase RNA-like ER kinase (PERK) or activating transcription factor 4 (ATF4) significantly reduced the production of angiogenesis mediators induced ..
  34. Su Q, Wang S, Gao H, Kazemi S, Harding H, Ron D, et al. Modulation of the eukaryotic initiation factor 2 alpha-subunit kinase PERK by tyrosine phosphorylation. J Biol Chem. 2008;283:469-75 pubmed
    The endoplasmic reticulum (ER)-resident protein kinase PERK attenuates protein synthesis in response to ER stress through the phosphorylation of translation initiation factor eIF2alpha at serine 51...
  35. Lin W, Lin Y, Li J, Fenstermaker A, Way S, Clayton B, et al. Oligodendrocyte-specific activation of PERK signaling protects mice against experimental autoimmune encephalomyelitis. J Neurosci. 2013;33:5980-91 pubmed publisher
    ..Activation of pancreatic endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic reticulum (ER) stress increases cell survival under various cytotoxic ..
  36. Mulvey M, Arias C, Mohr I. Maintenance of endoplasmic reticulum (ER) homeostasis in herpes simplex virus type 1-infected cells through the association of a viral glycoprotein with PERK, a cellular ER stress sensor. J Virol. 2007;81:3377-90 pubmed
    ..whereas the other arm activates the eIF-2alpha (alpha subunit of eukaryotic initiation factor 2) kinase PERK to transiently arrest production of new polypeptide clientele...
  37. Owen C, Kumar R, Zhang P, McGrath B, Cavener D, Krause G. PERK is responsible for the increased phosphorylation of eIF2alpha and the severe inhibition of protein synthesis after transient global brain ischemia. J Neurochem. 2005;94:1235-42 pubmed
    ..To address the role of the eIF2alpha kinase RNA-dependent protein kinase-like endoplasmic reticulum kinase (PERK) in the reperfused brain, transgenic mice with a targeted disruption of the Perk gene were subjected to 20 min of ..
  38. 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
    ..to endoplasmic reticulum (ER) stress or amino acid starvation by a mechanism requiring eIF2 kinases PEK (Perk or EIF2AK3) and GCN2 (EIF2AK4), respectively...
  39. 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
    ..Here we report that mutating the gene encoding the ER stress-activated eIF2alpha kinase PERK abolishes the phosphorylation of eIF2alpha in response to accumulation of malfolded proteins in the ER resulting in ..
  40. Cui W, Li J, Ron D, Sha B. The structure of the PERK kinase domain suggests the mechanism for its activation. Acta Crystallogr D Biol Crystallogr. 2011;67:423-8 pubmed publisher
    ..The ER-localized transmembrane kinase PERK is one of three major ER stress transducers...
  41. 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
    ..phosphorylation in response to a decrease in glucose concentration is primarily mediated by the activation of PERK [PKR (protein kinase RNA activated)-like endoplasmic reticulum kinase]...
  42. Trinh M, Kaphzan H, Wek R, Pierre P, Cavener D, Klann E. Brain-specific disruption of the eIF2? kinase PERK decreases ATF4 expression and impairs behavioral flexibility. Cell Rep. 2012;1:676-88 pubmed publisher
    Translational control depends on phosphorylation of eIF2? by PKR-like ER kinase (PERK). To examine the role of PERK in cognitive function, we selectively disrupted PERK expression in the adult mouse forebrain...
  43. 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
    ..When activated by their cognate upstream stress signals, the mammalian eIF2 kinases PERK and GCN2 repress translation of most mRNAs but selectively increase translation of Activating Transcription Factor ..
  44. Zhang W, Feng D, Li Y, Iida K, McGrath B, Cavener D. PERK EIF2AK3 control of pancreatic beta cell differentiation and proliferation is required for postnatal glucose homeostasis. Cell Metab. 2006;4:491-7 pubmed
    Mutations in PERK (EIF2AK3) result in permanent neonatal diabetes as well as several other anomalies that underlie the human Wolcott-Rallison syndrome, and these anomalies are mirrored in Perk knockout mice...
  45. 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
    ..PTP1B deficiency led to upregulation of PERK-eIF2? phosphorylation and IRE1?-XBP1 sub-arms of the unfolded protein response...
  46. Yang L, Xue Z, He Y, Sun S, Chen H, Qi L. A Phos-tag-based approach reveals the extent of physiological endoplasmic reticulum stress. PLoS ONE. 2010;5:e11621 pubmed publisher
    ..Our study may pave the foundation for future studies on physiological UPR, aid in the diagnosis of ER-associated diseases and improve and facilitate therapeutic strategies targeting UPR in vivo. ..
  47. Zhang Y, Zhang M, Wu J, Lei G, Li H. Transcriptional regulation of the Ufm1 conjugation system in response to disturbance of the endoplasmic reticulum homeostasis and inhibition of vesicle trafficking. PLoS ONE. 2012;7:e48587 pubmed publisher
    ..Taken together, our study provided critical insight into the regulatory mechanism of the Ufm1 system and established a direct link between this novel Ubl system and the ER network. ..
  48. Gass J, Jiang H, Wek R, Brewer J. The unfolded protein response of B-lymphocytes: PERK-independent development of antibody-secreting cells. Mol Immunol. 2008;45:1035-43 pubmed
    ..Three specific stress sensors, IRE1, PERK/PEK and ATF6, are central to the recognition of ER stress and induction of the UPR...
  49. Larhammar M, Huntwork Rodriguez S, Jiang Z, Solanoy H, Sengupta Ghosh A, Wang B, et al. Dual leucine zipper kinase-dependent PERK activation contributes to neuronal degeneration following insult. elife. 2017;6: pubmed publisher
    The PKR-like endoplasmic reticulum kinase (PERK) arm of the Integrated Stress Response (ISR) is implicated in neurodegenerative disease, although the regulators and consequences of PERK activation following neuronal injury are poorly ..
  50. Rojas Rivera D, Armisen R, Colombo A, Martinez G, Eguiguren A, Diaz A, et al. TMBIM3/GRINA is a novel unfolded protein response (UPR) target gene that controls apoptosis through the modulation of ER calcium homeostasis. Cell Death Differ. 2012;19:1013-26 pubmed publisher
    ..Tmbim3 mRNA levels are strongly upregulated in cellular and animal models of ER stress, controlled by the PERK signaling branch of the unfolded protein response...
  51. Vandewynckel Y, Laukens D, Devisscher L, Bogaerts E, Paridaens A, Van den Bussche A, et al. Placental growth factor inhibition modulates the interplay between hypoxia and unfolded protein response in hepatocellular carcinoma. BMC Cancer. 2016;16:9 pubmed publisher
    ..inhibitions of PlGF reduced the chaperone levels and the activation of the PKR-like endoplasmic reticulum kinase (PERK) pathway of the UPR in diethylnitrosamine-induced HCC...
  52. Upton J, Wang L, Han D, Wang E, Huskey N, Lim L, et al. IRE1? cleaves select microRNAs during ER stress to derepress translation of proapoptotic Caspase-2. Science. 2012;338:818-22 pubmed publisher
    ..Thus, IRE1? regulates translation of a proapoptotic protein through terminating microRNA biogenesis, and noncoding RNAs are part of the ER stress response. ..
  53. Radford H, Moreno J, Verity N, Halliday M, Mallucci G. PERK inhibition prevents tau-mediated neurodegeneration in a mouse model of frontotemporal dementia. Acta Neuropathol. 2015;130:633-42 pubmed publisher
    The PERK-eIF2α branch of the Unfolded Protein Response (UPR) mediates the transient shutdown of translation in response to rising levels of misfolded proteins in the endoplasmic reticulum...
  54. Stone S, Ho Y, Li X, Jamison S, Harding H, Ron D, et al. Dual role of the integrated stress response in medulloblastoma tumorigenesis. Oncotarget. 2016;7:64124-64135 pubmed publisher
    In response to endoplasmic reticulum (ER) stress, activation of pancreatic ER kinase (PERK) coordinates an adaptive program known as the integrated stress response (ISR) by phosphorylating translation initiation factor 2α (eIF2α)...
  55. Novosyadlyy R, Kurshan N, Lann D, Vijayakumar A, Yakar S, LeRoith D. Insulin-like growth factor-I protects cells from ER stress-induced apoptosis via enhancement of the adaptive capacity of endoplasmic reticulum. Cell Death Differ. 2008;15:1304-17 pubmed publisher
    ..augments the adaptive capacity of the ER by enhancing compensatory mechanisms such as the IRE1 alpha-, PERK- and ATF6-mediated arms of ER stress signalling...
  56. Wahlin K, Adler R, Zack D, Campochiaro P. Neurotrophic signaling in normal and degenerating rodent retinas. Exp Eye Res. 2001;73:693-701 pubmed
    ..by performing immunohistochemical staining for the phosphorylated form of extracellular receptor kinase (pERK) or c-fos after intravitreous injection of neurotrophic factors in wild type rats or mice, or those with inherited ..
  57. Wilding Crawford L, Tweedie Ables E, Oh Y, Boone B, Levy S, Gannon M. Gene expression profiling of a mouse model of pancreatic islet dysmorphogenesis. PLoS ONE. 2008;3:e1611 pubmed publisher
    ..This study provides a unique dataset that can act as a starting point for other investigators to explore the role of the identified genes in pancreatogenesis, islet morphogenesis and mature beta cell function. ..
  58. Yang W, Zhou X, Zimmermann H, Cavener D, Klann E, Ma T. Repression of the eIF2? kinase PERK alleviates mGluR-LTD impairments in a mouse model of Alzheimer's disease. Neurobiol Aging. 2016;41:19-24 pubmed publisher
    ..and that the mGluR-LTD failure is reversed by either genetically or pharmacologically suppressing the activity of PERK, a kinase for the mRNA translation factor eIF2?...
  59. Xiong G, Hindi S, Mann A, Gallot Y, Bohnert K, Cavener D, et al. The PERK arm of the unfolded protein response regulates satellite cell-mediated skeletal muscle regeneration. elife. 2017;6: pubmed publisher
    ..The UPR is relayed to the cell through the activation of PERK, IRE1/XBP1, and ATF6...
  60. 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. ..
  61. Guthrie L, Abiraman K, Plyler E, Sprenkle N, Gibson S, McFarland B, et al. Attenuation of PKR-like ER Kinase (PERK) Signaling Selectively Controls Endoplasmic Reticulum Stress-induced Inflammation Without Compromising Immunological Responses. J Biol Chem. 2016;291:15830-40 pubmed publisher
    ..evidence that inhibition or genetic haploinsufficiency of protein kinase R-like endoplasmic reticulum kinase (PERK) can selectively control inflammation brought on by ER stress without impinging on UPR-dependent survival and ..