PERK

Summary

Gene Symbol: PERK
Description: eukaryotic translation initiation factor 2 alpha kinase 3
Alias: PEK, PERK, WRS, eukaryotic translation initiation factor 2-alpha kinase 3, PRKR-like endoplasmic reticulum kinase, pancreatic EIF2-alpha kinase
Species: human

Top Publications

  1. ncbi Nck-1 selectively modulates eIF2alphaSer51 phosphorylation by a subset of eIF2alpha-kinases
    Eric Cardin
    Polypeptide Laboratory, Department of Experimental Medicine, McGill University, Montreal, Canada
    FEBS J 274:5865-75. 2007
  2. pmc Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control
    Y Shi
    Diabetes Research, Endocrine Division, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA
    Mol Cell Biol 18:7499-509. 1998
  3. pmc Hepatic CYP3A suppression by high concentrations of proteasomal inhibitors: a consequence of endoplasmic reticulum (ER) stress induction, activation of RNA-dependent protein kinase-like ER-bound eukaryotic initiation factor 2alpha (eIF2alpha)-kinase (PERK
    Poulomi Acharya
    Dept of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA
    Mol Pharmacol 76:503-15. 2009
  4. ncbi EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome
    M Delepine
    Centre National de Genotypage, Evry, France
    Nat Genet 25:406-9. 2000
  5. ncbi Dimerization and release of molecular chaperone inhibition facilitate activation of eukaryotic initiation factor-2 kinase in response to endoplasmic reticulum stress
    Kun Ma
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    J Biol Chem 277:18728-35. 2002
  6. ncbi Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene
    Anna Biason-Lauber
    University Children s Hospital, Division of Pediatric Endocrinology Diabetology, Steinwiesstrasse 75, 8032 Zurich, Switzerland
    Diabetes 51:2301-5. 2002
  7. pmc 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
    Nicole Pavio
    Howard Hughes Medical Institute, Department of Molecular Microbiology and Immunology, School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    J Virol 77:3578-85. 2003
  8. pmc Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival
    Sara B Cullinan
    The Leonard and Madlyn Abramson Family Cancer Research Institute and Cancer Center, Department of Cancer Biology, University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania 19104, USA
    Mol Cell Biol 23:7198-209. 2003
  9. ncbi Wolcott-Rallison Syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity
    Valérie Senée
    Génétique des Maladies Infectieuses et Autoimmunes, INSERM E102, Institut Pasteur, Paris, France
    Diabetes 53:1876-83. 2004
  10. pmc ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth
    Meixia Bi
    Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    EMBO J 24:3470-81. 2005

Research Grants

  1. Human Tryptophanyl-tRNA Synthetase-A Functional Analysis
    Jerry Johnson; Fiscal Year: 2006
  2. MELANOMA CELL SURFACE PROTEOGLYCANS IN METASTASIS
    James B McCarthy; Fiscal Year: 2010
  3. Randal J Kaufman; Fiscal Year: 2014
  4. Constantinos Koumenis; Fiscal Year: 2016
  5. Translational Machinery in Stress Signaling and Tumor Suppression
    THOMAS J contact BEGLEY; Fiscal Year: 2010
  6. Elucidating the role of the eIF2alpha kinase PERK in synaptic plasticity and memo
    MY AI TRINH; Fiscal Year: 2010
  7. Drug-like small molecule modulators of the Integrated Stress Response
    David Ron; Fiscal Year: 2010
  8. Tracy G Anthony; Fiscal Year: 2015
  9. Makoto Miyazaki; Fiscal Year: 2016
  10. Bertal H Aktas; Fiscal Year: 2015

Detail Information

Publications437 found, 100 shown here

  1. ncbi Nck-1 selectively modulates eIF2alphaSer51 phosphorylation by a subset of eIF2alpha-kinases
    Eric Cardin
    Polypeptide Laboratory, Department of Experimental Medicine, McGill University, Montreal, Canada
    FEBS J 274:5865-75. 2007
    ..In mammals, four eIF2alpha-kinases [PKR-like endoplasmic reticulum kinase (PERK), dsRNA-activated protein kinase (PKR), heme regulated inhibitor (HRI) and general control nonderepressible-2 (GCN2)..
  2. pmc Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control
    Y Shi
    Diabetes Research, Endocrine Division, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA
    Mol Cell Biol 18:7499-509. 1998
    ..from rat pancreatic islet cells that encodes a new related kinase, which we term pancreatic eIF-2alpha kinase, or PEK. In addition to a catalytic domain with sequence and structural features conserved among eIF-2alpha kinases, PEK ..
  3. pmc Hepatic CYP3A suppression by high concentrations of proteasomal inhibitors: a consequence of endoplasmic reticulum (ER) stress induction, activation of RNA-dependent protein kinase-like ER-bound eukaryotic initiation factor 2alpha (eIF2alpha)-kinase (PERK
    Poulomi Acharya
    Dept of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA
    Mol Pharmacol 76:503-15. 2009
    ..MG132 concentrations, such CYP3A suppression could be due to ER stress induction, so we monitored the activity of PERK [PKR (RNA-dependent protein kinase)-like ER kinase (EIF2AK3)], the ER stress-activated eukaryotic initiation factor ..
  4. ncbi EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome
    M Delepine
    Centre National de Genotypage, Evry, France
    Nat Genet 25:406-9. 2000
    Wolcott-Rallison syndrome (WRS) is a rare, autosomal recessive disorder characterized by permanent neonatal or early infancy insulin-dependent diabetes. Epiphyseal dysplasia, osteoporosis and growth retardation occur at a later age...
  5. ncbi Dimerization and release of molecular chaperone inhibition facilitate activation of eukaryotic initiation factor-2 kinase in response to endoplasmic reticulum stress
    Kun Ma
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    J Biol Chem 277:18728-35. 2002
    ..This study addresses the mechanisms activating PEK, also designated PERK or EIF2AK3...
  6. ncbi Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene
    Anna Biason-Lauber
    University Children s Hospital, Division of Pediatric Endocrinology Diabetology, Steinwiesstrasse 75, 8032 Zurich, Switzerland
    Diabetes 51:2301-5. 2002
    Wolcott-Rallison syndrome (WRS) is an autosomal recessive disorder characterized by neonatal or early infancy type 1 diabetes, epiphyseal dysplasia, and growth retardation...
  7. pmc 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
    Nicole Pavio
    Howard Hughes Medical Institute, Department of Molecular Microbiology and Immunology, School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    J Virol 77:3578-85. 2003
    ..Here we show that the PKR-like ER-resident kinase (PERK) binds to and is also inhibited by E2...
  8. pmc Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival
    Sara B Cullinan
    The Leonard and Madlyn Abramson Family Cancer Research Institute and Cancer Center, Department of Cancer Biology, University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania 19104, USA
    Mol Cell Biol 23:7198-209. 2003
    Activation of PERK following the accumulation of unfolded proteins in the endoplasmic reticulum (ER) promotes translation inhibition and cell cycle arrest...
  9. ncbi Wolcott-Rallison Syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity
    Valérie Senée
    Génétique des Maladies Infectieuses et Autoimmunes, INSERM E102, Institut Pasteur, Paris, France
    Diabetes 53:1876-83. 2004
    Wolcott-Rallison syndrome (WRS) is a rare autosomal-recessive disorder characterized by the association of permanent neonatal or early-infancy insulin-dependent diabetes, multiple epiphyseal dysplasia and growth retardation, and other ..
  10. pmc ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth
    Meixia Bi
    Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    EMBO J 24:3470-81. 2005
    ..Inactivation of ISR signaling by mutations in the ER kinase PERK and the translation initiation factor eIF2alpha or by a dominant-negative PERK impairs cell survival under extreme ..
  11. ncbi Carbon monoxide induces heme oxygenase-1 via activation of protein kinase R-like endoplasmic reticulum kinase and inhibits endothelial cell apoptosis triggered by endoplasmic reticulum stress
    Ki Mo Kim
    Department of Immunology, Wonkwang University School of Medicine, Iksan, Chunbug 570 749, Republic of Korea
    Circ Res 101:919-27. 2007
    ..exogenous CO activated Nrf2 through the phosphorylation of protein kinase R-like endoplasmic reticulum kinase (PERK), resulting in HO-1 expression...
  12. ncbi PERK-dependent regulation of HSP70 expression and the regulation of autophagy
    Margaret A Park
    Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, USA
    Autophagy 4:364-7. 2008
    ..It notes that in PKR-like endoplasmic reticulum kinase null cells (PERK-/-) the lethality of OSU is attenuated...
  13. pmc Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families
    Oscar Rubio-Cabezas
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter EX2 5DW, United Kingdom
    J Clin Endocrinol Metab 94:4162-70. 2009
    Mutations in EIF2AK3 cause Wolcott-Rallison syndrome (WRS), a rare recessive disorder characterized by early-onset diabetes, skeletal abnormalities, and liver dysfunction...
  14. pmc Activation of PERK signaling attenuates Abeta-mediated ER stress
    Do Yeon Lee
    Department of Anatomy and Cell Biology, College of Medicine, Chung Ang University, Seoul, Korea
    PLoS ONE 5:e10489. 2010
    ..Abeta mediated UPR pathway accompanies the activation of protective pathways such as Grp78/Bip and PERK-eIF2alpha pathway, as well as the apoptotic pathways of the UPR such as CHOP and caspase-4...
  15. pmc Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy
    Günter U Höglinger
    Department of Neurology, Philipps Universitat, Marburg, Germany
    Nat Genet 43:699-705. 2011
    ..The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component...
  16. pmc A functional haplotype in EIF2AK3, an ER stress sensor, is associated with lower bone mineral density
    Jie Liu
    Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    J Bone Miner Res 27:331-41. 2012
    ..Taken together, our results suggest that common nonsynonymous sequence variants in EIF2AK3 have a modest effect on ER stress response and may contribute to the risk for low BMD through this mechanism...
  17. pmc The unfolded protein response induces the angiogenic switch in human tumor cells through the PERK/ATF4 pathway
    Yugang Wang
    Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109 1078, USA
    Cancer Res 72:5396-406. 2012
    ..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 ..
  18. pmc Regulation of autophagy during ECM detachment is linked to a selective inhibition of mTORC1 by PERK
    A Avivar-Valderas
    Department of Medicine and Department of Otolaryngology, Tisch Cancer Institute, Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, NY, USA
    Oncogene 32:4932-40. 2013
    ..However, the mechanisms controlling detachment-induced autophagy remain unclear. Here we uncover that the kinase PERK rapidly promotes autophagy in ECM-detached cells by activating AMP-activated protein kinase (AMPK), resulting in ..
  19. pmc Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response
    Tetsuya Okada
    Graduate School of Biostudies, Kyoto University, 46 29 Yoshida Shimoadachi, Sakyo ku, Kyoto 606 8304, Japan
    Biochem J 366:585-94. 2002
    ..The ER-membrane-bound protein kinase double-stranded RNA-activated protein kinase-like ER kinase (PERK)-mediated signalling pathway appeared to be responsible for induction of the remaining genes, which are not ..
  20. pmc Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha
    Constantinos Koumenis
    Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    Mol Cell Biol 22:7405-16. 2002
    ..The endoplasmic reticulum (ER)-resident eIF2alpha kinase PERK was hyperphosphorylated upon hypoxic stress, and overexpression of wild-type PERK increased the levels of hypoxia-..
  21. pmc The role of nitric-oxide synthase in the regulation of UVB light-induced phosphorylation of the alpha subunit of eukaryotic initiation factor 2
    Wei Lu
    Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA
    J Biol Chem 284:24281-8. 2009
    ..Both eIF2 kinases, protein kinase-like endoplasmic reticulum kinase (PERK) and general control of nonderepressible protein kinase 2 (GCN2), have been shown to phosphorylate eIF2alpha in ..
  22. doi Wolcott-Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature
    M Nuri Ozbek
    Cukurova University, Pediatric Endocrinology and Metabolism, Balcali, Adana, Turkey
    Pediatr Diabetes 11:279-85. 2010
    Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by an early-infancy-onset diabetes mellitus associated with a variety of multisystemic clinical manifestations...
  23. doi Two novel mutations in the EIF2AK3 gene in children with Wolcott-Rallison syndrome
    Andre F Reis
    Endocrinology Unit, Federal University of Sao Paulo UNIFESP, Sao Paulo, Brazil
    Pediatr Diabetes 12:187-91. 2011
    Wolcott-Rallison syndrome (WRS, OMIM 226980) is a rare autosomal recessive disorder characterized by permanent neonatal diabetes mellitus, epiphyseal dysplasia, and other multisystemic clinical manifestations...
  24. ncbi A novel EIF2AK3 mutation leading to Wolcott-Rallison syndrome in a Chinese child
    Yanmei Sang
    Department of Endocrinology, Beijing Children s Hospital Affiliated to Capital Medical University, Bejiing, PR China
    J Pediatr Endocrinol Metab 24:181-4. 2011
    Mutations in the EIF2AK3 gene are known to cause Wolcott-Rallison syndrome (WRS), a rare recessive disorder characterized by early-onset diabetes, skeletal abnormalities, and liver dysfunction...
  25. pmc Hepatic heme-regulated inhibitor (HRI) eukaryotic initiation factor 2alpha kinase: a protagonist of heme-mediated translational control of CYP2B enzymes and a modulator of basal endoplasmic reticulum stress tone
    Poulomi Acharya
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA
    Mol Pharmacol 77:575-92. 2010
    ..ER) stress as revealed by the activation of ER stress-inducible RNA-dependent protein kinase-like ER-integral (PERK) eIF2 alpha-kinase, and induction of hepatic protein ubiquitination and ER chaperones Grp78 and Grp94...
  26. ncbi [Experimental studies of polymorphonuclear leukocyte on mandibular bone infection model in rabbit]
    A Abe
    Department of Oral and Maxillofacial Surgery I, Nippon Dental University, School of Dentistry at Tokyo
    Kansenshogaku Zasshi 72:526-35. 1998
    ..1) The number of leukocytes increased after treatment, reached a perk on day 3, gradually diminished later, but remained slightly higher than the baseline level on day 7, with ..
  27. ncbi Role of circadian rhythm and endogenous melatonin in pathogenesis of acute gastric bleeding erosions induced by stress
    T Brzozowski
    Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, Cracow, Poland
    J Physiol Pharmacol 58:53-64. 2007
    ..pineal glands and those with removed pineal glands (pinealectomy) exposed to water immersion and restraint stress (WRS) at both, day and night hours, we studied the effect of light and nocturnal melatonin on the formation of these ..
  28. ncbi Molecular pathways of protein synthesis inhibition during brain reperfusion: implications for neuronal survival or death
    Donald J DeGracia
    Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
    J Cereb Blood Flow Metab 22:127-41. 2002
    ..of the alpha subunit of eIF2 [eIF2(alphaP)] by the endoplasmic reticulum transmembrane eIF2alpha kinase PERK occurs immediately on reperfusion and inhibits translation initiation...
  29. ncbi Surgical and functional results of spine fusion in spinal muscular atrophy
    J C Brown
    Spine Deformity Service, Rancho Los Amigos Medical Center, Downey, California
    Spine (Phila Pa 1976) 14:763-70. 1989
    ..Surgical patients never approached their preoperative skill levels. Therapy evaluations further demonstrated that there were no difference in function between either operative group...
  30. ncbi Regulation of hemoglobin synthesis and proliferation of differentiating erythroid cells by heme-regulated eIF-2alpha kinase
    J S Crosby
    Harvard Massachusetts Institute of Technology, Division of Health Sciences and Technology, Cambridge MA, USA
    Blood 96:3241-8. 2000
    ..These results directly demonstrate the importance of HRI in the regulation of protein synthesis in immature erythroid cells and suggest a role of HRI in the regulation of the numbers of matured erythroid cells...
  31. ncbi Two heme-binding domains of heme-regulated eukaryotic initiation factor-2alpha kinase. N terminus and kinase insertion
    M Rafie-Kolpin
    Harvard MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Biol Chem 275:5171-8. 2000
    ..Thus, both the N terminus and the kinase insertion, which are unique to HRI, are involved in the heme binding and the heme regulation of HRI...
  32. ncbi CO binding study of mouse heme-regulated eIF-2alpha kinase: kinetics and resonance Raman spectra
    Jotaro Igarashi
    Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2 1 1 Katahira, Aoba ku, Sendai 980 8577, Japan
    Biochim Biophys Acta 1650:99-104. 2003
    ..Resonance Raman spectra suggest that the Fe-C-O adopts an almost linear and upright structure and that the bound CO interacts only weakly with nearby amino acid residues...
  33. doi Stress-induced overexpression of the heme-regulated eIF-2alpha kinase is regulated by Elk-1 activated through ERK pathway
    Vir B Singh
    Department of Biotechnology, University of Pune, Ganeshkhind, Pune, Maharashtra, India
    Biochem Biophys Res Commun 379:710-5. 2009
    ..We also demonstrate the involvement of ERK pathway in activating Elk-1 during stress resulting in an over expression of hHRI...
  34. doi Elucidation of the heme binding site of heme-regulated eukaryotic initiation factor 2alpha kinase and the role of the regulatory motif in heme sensing by spectroscopic and catalytic studies of mutant proteins
    Jotaro Igarashi
    Institute of Multidisciplinary Research for Advanced Materials, Tohoku University at Katahira, Sendai 980 8577, Japan
    J Biol Chem 283:18782-91. 2008
    ....
  35. pmc GCN2 protein kinase is required to activate amino acid deprivation responses in mice treated with the anti-cancer agent L-asparaginase
    Piyawan Bunpo
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Evansville, Indiana 47712, USA
    J Biol Chem 284:32742-9. 2009
    ..study were to assess the role of the eIF2 kinases and protein kinase R-like endoplasmic reticulum resident kinase (PERK) in controlling AADR to asparaginase and to compare the effects of asparaginase on mTORC1 to that of rapamycin...
  36. ncbi Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 2alpha kinase
    J J Berlanga
    Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid, Spain
    Eur J Biochem 265:754-62. 1999
    ..inhibitor (HRI), the interferon-inducible RNA-dependent kinase (PKR) and the endoplasmic reticulum-resident kinase (PERK)...
  37. ncbi The haem-regulated eukaryotic initiation factor 2alpha kinase: a molecular indicator of lead-toxicity anaemia in rabbits
    Sanjay Anand
    Department of Biotechnology, University of Pune, Pune 411 007, India
    Biotechnol Appl Biochem 36:57-62. 2002
    ..These observations further reiterate the use of HRI as a potential indicator for drug- and heavy-metal-induced anaemia in humans...
  38. pmc Endoplasmic reticulum stress response mediated by the PERK-eIF2(alpha)-ATF4 pathway is involved in osteoblast differentiation induced by BMP2
    Atsushi Saito
    From the Department of Biochemistry, Division of Genome Radiobiology and Medical Science, Graduate School of Biomedical Science, University of Hiroshima, Hiroshima 734 8553, Japan
    J Biol Chem 286:4809-18. 2011
    ..Double stranded RNA activated protein kinase (PKR)-like endoplasmic reticulum kinase (PERK) is a major transducer of the ER stress response and directly phosphorylates eIF2α, resulting in translational ..
  39. ncbi Identification of Cys385 in the isolated kinase insertion domain of heme-regulated eIF2 alpha kinase (HRI) as the heme axial ligand by site-directed mutagenesis and spectral characterization
    Kyoko Hirai
    Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai 980 8577, Japan
    J Inorg Biochem 101:1172-9. 2007
    ..Based on these spectroscopic findings, we conclude that Cys385 is an axial ligand of isolated KI...
  40. ncbi Characterization of the hemin-sensitive eukaryotic initiation factor 2alpha kinase from mouse nonerythroid cells
    J J Berlanga
    Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid, Canto Blanco, 28049 Madrid, Spain
    J Biol Chem 273:32340-6. 1998
    ..These results provide strong evidence that mHRI is a ubiquitous eIF2alpha kinase of mammalian cells, suggesting that it could play important roles in the translational regulation of nonerythroid tissues...
  41. pmc 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
    Shun Hsin Liang
    Department of Biology, The Pennsylvania State University, University Park, PA 16802, USA
    Biochem J 393:201-9. 2006
    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 ..
  42. ncbi Gastric ulcer healing and stress-lesion preventive properties of pioglitazone are attenuated in diabetic rats
    P C Konturek
    Department of Medicine, Thuringia Clinic Georgius Agricola Saalfeld, Teaching Hospital University Jena, Germany
    J Physiol Pharmacol 61:429-36. 2010
    ..on healing of acetic acid-induced gastric ulcers and prevention of acute water immersion and restraint stress (WRS)-induced gastric lesions in normal rats and those with streptozotocin (STZ)-induced diabetes mellitus; 2) to assess ..
  43. ncbi Lead-induced upregulation of the heme-regulated eukaryotic initiation factor 2alpha kinase is compromised by hemin in human K562 cells
    Angshuman Sarkar
    Department of Biotechnology, University of Pune, Pune 411 007, India
    Biochim Biophys Acta 1732:15-22. 2005
    ..Hemin may thus be useful for alleviation of stress-induced inhibition of protein synthesis...
  44. ncbi Brain ischemia and reperfusion activates the eukaryotic initiation factor 2alpha kinase, PERK
    R Kumar
    Department of Emergency Medicine, Wayne State University, Detroit, Michigan 48201, USA
    J Neurochem 77:1418-21. 2001
    ..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...
  45. ncbi Endoplasmic reticulum: a primary target in various acute disorders and degenerative diseases of the brain
    Wulf Paschen
    Department of Experimental Neurology, Max Planck Institute for Neurological Research, 50931 Koeln, Germany
    Cell Calcium 34:365-83. 2003
    ..UPR is characterized by activation of two ER-resident kinases, PKR-like ER kinase (PERK) and IRE1...
  46. pmc Cloning of the cDNA of the heme-regulated eukaryotic initiation factor 2 alpha (eIF-2 alpha) kinase of rabbit reticulocytes: homology to yeast GCN2 protein kinase and human double-stranded-RNA-dependent eIF-2 alpha kinase
    J J Chen
    Harvard Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge
    Proc Natl Acad Sci U S A 88:7729-33. 1991
    ..In addition, HRI has an unusually high degree of homology to three protein kinases (NimA, Wee1, and CDC2) that are involved in the regulation of the cell cycle...
  47. pmc 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
    Peichuan Zhang
    Department of Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA
    Mol Cell Biol 22:3864-74. 2002
    ..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 ..
  48. ncbi Time course of neurotrophic factor upregulation and retinal protection against light-induced damage after optic nerve section
    Krisztina Valter
    CNS Stability and Degeneration Group, Research School of Biological Sciences, The Australian National University, Canberra City, Canberra, ACT 2601, Australia
    Invest Ophthalmol Vis Sci 46:1748-54. 2005
    ..To assess neurotrophic factor upregulation in the retina after damage to the optic nerve and relate that regulation to changes in photoreceptor stability and function...
  49. pmc Amino acid microsequencing of internal tryptic peptides of heme-regulated eukaryotic initiation factor 2 alpha subunit kinase: homology to protein kinases
    J J Chen
    Harvard MIT Division of Health Sciences, Cambridge, MA 02139
    Proc Natl Acad Sci U S A 88:315-9. 1991
    ..Since little is known about the function of conserved domain IX, P-74 peptide may be useful in elucidating the role of this domain of protein kinases...
  50. doi Activation of eukaryotic initiation factor-2 α-kinases in okadaic acid-treated neurons
    S M Kim
    Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Korea
    Neuroscience 169:1831-9. 2010
    ..kinases, including double-stranded RNA-dependent protein kinase (PKR), PKR-like endoplasmic reticulum kinase (PERK), amino acids-regulated eIF2 alpha kinase (GCN2) and heme-regulated eIF2 alpha kinase (HRI)...
  51. ncbi A novel mutation in the EIF2AK3 gene with variable expressivity in two patients with Wolcott-Rallison syndrome
    F Durocher
    Cancer Genomics Laboratory, Oncology and Molecular Endocrinology Research Centre, Centre Hospitalier Universitaire de Quebec and Laval University, Quebec, Canada
    Clin Genet 70:34-8. 2006
    ..This supports the idea that there is no simple relationship among clinical manifestations and EIF2AK3 mutations...
  52. ncbi [Empirical study in the relation of gastric mucosal lesion with gastric emptying and gastric acid secretion]
    Hong Feng Zhang
    Department of Abdominal Surgery, Affiliated Tumor Hospital, Harbin Medical University, Harbin, China
    Zhonghua Wei Chang Wai Ke Za Zhi 11:472-6. 2008
    To study the precise cause and the specific procedure about gastric mucosal lesion in rats with water immersion-restraint stress(WRS).
  53. ncbi Comparison of tobramycin 0.3%/dexamethasone 0.1% and tobramycin 0.3%/loteprednol 0.5% in the management of blepharo-keratoconjunctivitis
    Steven S Rhee
    University of Pittsburgh School of Medicine, Department of Ophthalmology, UPMC Eye Center, Pittsburgh, PA 15213 2588, USA
    Adv Ther 24:60-7. 2007
    ..for 4 components: blepharitis, conjunctivitis, ocular discharge, and corneal punctate epithelial keratopathy (PEK). Only those patients with moderate to extensive inflammation (cumulative score >6) were included in the study...
  54. pmc Phosphorylation of eukaryotic initiation factor 2 by heme-regulated inhibitor kinase-related protein kinases in Schizosaccharomyces pombe is important for fesistance to environmental stresses
    Ke Zhan
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    Mol Cell Biol 22:7134-46. 2002
    ..These results demonstrate that HRI-related enzymes are not unique to vertebrates and suggest that these eIF2alpha kinases are important participants in diverse stress response pathways in some lower eukaryotes...
  55. pmc Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 is required for activation of NF-kappaB in response to diverse cellular stresses
    Hao Yuan Jiang
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    Mol Cell Biol 23:5651-63. 2003
    ..impaired protein folding and assembly in the endoplasmic reticulum (ER), phosphorylation of eIF2alpha by PEK (Perk or EIF2AK3) is essential for induction of NF-kappaB transcriptional activity...
  56. pmc PERK eIF2 alpha kinase is required to regulate the viability of the exocrine pancreas in mice
    Kaori Iida
    Department of History of Science and Technology, Johns Hopkins University, Baltimore, MD 21218, USA
    BMC Cell Biol 8:38. 2007
    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...
  57. pmc Sensory denervation modulates eIF-2 alpha kinase expression in the rabbit lacrimal gland
    Doan H Nguyen
    LSU Eye Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
    Curr Eye Res 31:287-95. 2006
    ..We used differential display of mRNA to identify genes associated with protein synthesis and secretion that may be altered in this situation...
  58. pmc eIF2alpha kinases GCN2 and PERK modulate transcription and translation of distinct sets of mRNAs in mouse liver
    An N Dang Do
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, USA
    Physiol Genomics 38:328-41. 2009
    ..HRI), double-stranded RNA-activated protein kinase (PKR), and PKR-like endoplasmic reticulum-resident kinase (PERK)...
  59. ncbi Exposure and nasal inflammation in workers heating polyurethane
    Margareta Littorin
    Department of Occupational and Environmental Medicine, University Hospital, 221 85 Lund, Sweden
    Int Arch Occup Environ Health 75:468-74. 2002
    ..To test the hypothesis that exposure to thermal-degradation products of polyurethane (PUR), particularly isocyanates, induced nasal inflammation...
  60. ncbi PERK is responsible for the increased phosphorylation of eIF2alpha and the severe inhibition of protein synthesis after transient global brain ischemia
    Cheri R Owen
    Department of Emergency Medicine, Wayne State University, Detroit, Michigan 48201, USA
    J Neurochem 94:1235-42. 2005
    ..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 ..
  61. doi Autophosphorylation of heme-regulated eukaryotic initiation factor 2α kinase and the role of the modification in catalysis
    Jotaro Igarashi
    Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Japan
    FEBS J 278:918-28. 2011
    ..Accordingly, we suggest that Tyr193, Thr485 and Thr490 are essential residues in the catalysis...
  62. doi Mismatch between changes in baicalein-induced memory-related biochemical parameters and behavioral consequences in mouse
    Se Jin Park
    Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, 1 Hoeki dong, Dongdaemoon Ku, Seoul 130 701, Republic of Korea
    Brain Res 1355:141-50. 2010
    ..o.) as compared to vehicle significantly increased the expression of phosphorylated ERK (pERK), phosphorylated CREB (pCREB), and BDNF but did not increase phosphorylated Akt expression in the hippocampus of ..
  63. pmc Glucosamine-induced endoplasmic reticulum stress attenuates apolipoprotein B100 synthesis via PERK signaling
    Wei Qiu
    Molecular Structure and Function, Research Institute, The Hospital for Sick Children, University of Toronto, Ontario, M5G 1X8, Canada
    J Lipid Res 50:1814-23. 2009
    ..47: 1749-1761). Here, we report that glucosamine also regulates apoB100 protein synthesis via ER-stress-induced PERK activation...
  64. ncbi Induction of Grp78/BiP by translational block: activation of the Grp78 promoter by ATF4 through and upstream ATF/CRE site independent of the endoplasmic reticulum stress elements
    Shengzhan Luo
    Department of Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine, Los Angeles, California 90089 9176, USA
    J Biol Chem 278:37375-85. 2003
    ..cells respond to endoplasmic reticulum (ER) stress by attenuation of protein translation mediated through the PERK-eIF2alpha pathway and transcriptional activation of genes such as Grp78/BiP encoding ER chaperone proteins...
  65. pmc Cisplatin enhances protein kinase R-like endoplasmic reticulum kinase- and CD95-dependent melanoma differentiation-associated gene-7/interleukin-24-induced killing in ovarian carcinoma cells
    Adly Yacoub
    Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298 0035, USA
    Mol Pharmacol 77:298-310. 2010
    ..Expression of MDA-7/IL-24 induced phosphorylation of protein kinase R-like endoplasmic reticulum kinase (PERK) and eukaryotic initiation factor2alpha (eIF2alpha)...
  66. ncbi Mucosal strengthening activity of central and peripheral melatonin in the mechanism of gastric defense
    I Brzozowska
    Department of Anatomy, Jagiellonian University Medical College, Cracow, Poland
    J Physiol Pharmacol 60:47-56. 2009
    ..manner the formation of on gastric lesions induced by topical irritants and water immersion restraint stress (WRS)...
  67. doi Acetaldehyde elicits ERK phosphorylation in the rat nucleus accumbens and extended amygdala
    Stefania Vinci
    Department of Toxicology, University of Cagliari, 09124 Cagliari, Italy
    Synapse 64:916-27. 2010
    ..In a recent study, we have shown that ethanol elicits the phosphorylation of extracellular signal-regulated kinase (pERK) in the nucleus accumbens and extended amygdala, via a dopamine D(1) receptor-mediated mechanism...
  68. doi The PERK/eIF2 alpha signaling pathway of Unfolded Protein Response is essential for N-(4-hydroxyphenyl)retinamide (4HPR)-induced cytotoxicity in cancer cells
    Wai Lung Lai
    Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong, China
    Exp Cell Res 314:1667-82. 2008
    ..These effects of 4HPR could be abolished by the over-expression of dominant negative mutants of PERK or eIF2 alpha...
  69. doi EIF2alpha and caspase-12 activation are involved in oxygen-glucose-serum deprivation/restoration-induced apoptosis of spinal cord astrocytes
    Ailiang Zhang
    Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China
    Neurosci Lett 478:32-6. 2010
    ..Although many studies have shown that oxygen-glucose deprivation (OGD) can induce astrocyte apoptosis, the role of PERK/eIF2 alpha/ATF4 integrated stress response (ISR) in astrocyte apoptosis mediated by oxygen-glucose-serum ..
  70. ncbi Translational control and the unfolded protein response
    Ronald C Wek
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    Antioxid Redox Signal 9:2357-71. 2007
    ..b>PERK (PEK/EIF2AK3) mediates the translational control arm of the UPR by enhancing phosphorylation of eIF2...
  71. ncbi Hsp90 mediates activation of the heme regulated eIF-2 alpha kinase during oxidative stress
    A P Kulkarni
    Department of Biotechnology, University of Pune, Pune 411 007, India
    Indian J Biochem Biophys 47:67-74. 2010
    ..Thus, we demonstrate that Hsps play an important role in the regulation of initiation of protein synthesis during oxidative stress...
  72. pmc PERK activation at low glucose concentration is mediated by SERCA pump inhibition and confers preemptive cytoprotection to pancreatic β-cells
    Claire E Moore
    Department of Cell Physiology and Pharmacology, The Henry Wellcome Building, University of Leicester, University Road, Leicester LE1 9HN, United Kingdom
    Mol Endocrinol 25:315-26. 2011
    Protein kinase R-like ER kinase (PERK) is activated at physiologically low glucose concentrations in pancreatic β-cells...
  73. pmc Heme-regulated eIF2alpha kinase modifies the phenotypic severity of murine models of erythropoietic protoporphyria and beta-thalassemia
    An Ping Han
    Harvard Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Clin Invest 115:1562-70. 2005
    ..Our findings also demonstrate that translational regulation could play a critical role in the clinical manifestation of rbc diseases...
  74. pmc Regulation of protein synthesis by the heme-regulated eIF2alpha kinase: relevance to anemias
    Jane Jane Chen
    Harvard Massachusetts Institute of Technology MIT Division of Health Sciences and Technology HST, MIT, Cambridge, MA 02139, USA
    Blood 109:2693-9. 2007
    ..The protective role of HRI may be more common among red cell disorders...
  75. ncbi Role of the endoplasmic reticulum unfolded protein response in glomerular epithelial cell injury
    Andrey V Cybulsky
    Department of Medicine, McGill University Health Centre, McGill University, Montreal, Quebec H3A 1A1, Canada
    J Biol Chem 280:24396-403. 2005
    ..e. activation of protein kinase R-like ER kinase (PERK or pancreatic ER kinase), which phosphorylates eukaryotic translation initiation factor 2-alpha (eIF2alpha), ..
  76. ncbi Agonist of peroxisome proliferator-activated receptor gamma (PPAR-gamma): a new compound with potent gastroprotective and ulcer healing properties
    Tomasz Brzozowski
    Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31 531 Cracow, Poland
    Inflammopharmacology 13:317-30. 2005
    ..5 h of water immersion and restraint stress (WRS) with or without pretreatment with indomethacin (5 mg/kg i.p...
  77. ncbi Characterization of heme-regulated eIF2alpha kinase: roles of the N-terminal domain in the oligomeric state, heme binding, catalysis, and inhibition
    Marketa Miksanova
    Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai 980 8577, Japan
    Biochemistry 45:9894-905. 2006
    ..Finally, we found that HRI is inhibited by bilirubin at physiological/pathological levels (IC(50) = 20 microM). The roles of the N-terminal domain and the binding of heme in the structural and functional properties of HRI are discussed...
  78. pmc Inhibition of human pancreatic ribonuclease by the human ribonuclease inhibitor protein
    R Jeremy Johnson
    Department of Biochemistry, University of Wisconsin Madison, Madison, WI 53706 1544, USA
    J Mol Biol 368:434-49. 2007
    ..Together, these results provide new insight into an unusual and important protein-protein interaction, and could expedite the development of human ribonucleases as chemotherapeutic agents...
  79. ncbi Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6alpha and XBP1
    Keisuke Yamamoto
    Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606 8502, Japan
    Dev Cell 13:365-76. 2007
    Metazoans express three unfolded protein response transducers (IRE1, PERK, and ATF6) ubiquitously to cope with endoplasmic reticulum (ER) stress...
  80. ncbi Viral subversion of immunogenic cell death
    Oliver Kepp
    INSERM, U848, Villejuif, France
    Cell Cycle 8:860-9. 2009
    ..g., the eIF2alpha-phosphorylating kinase PERK), the apoptotic machinery (e.g...
  81. doi Regulation and function of neuronal GTP-Ras in facial motor nerve regeneration
    Milan Makwana
    Perinatal Brain Repair Group, Department of Obstetrics and Gynaecology, EGA Institute of Women s Health, University College London, London, UK
    J Neurochem 108:1453-63. 2009
    ..9%). Similar increase was also observed in the pERK but not pAKT targets of the Ras cascade...
  82. pmc Activation of the unfolded protein response contributes toward the antitumor activity of vorinostat
    Soumen Kahali
    Radiation Oncology, H Lee Moffitt Cancer Center, Tampa, FL 33612, USA
    Neoplasia 12:80-6. 2010
    ..activation of its client protein double-stranded RNA-activated protein-like endoplasmic reticulum kinase (PERK)...
  83. doi Superoxide generated by lysophosphatidylcholine induces endothelial nitric oxide synthase downregulation in human endothelial cells
    Shinkyu Choi
    Department of Physiology and Medical Research Center, School of Medicine, Ewha Womans University, Seoul, Republic of Korea
    Cell Physiol Biochem 25:233-40. 2010
    ..levels of eNOS, superoxide dismutase1 (SOD1), catalase, and phospho-extracellular signal regulated kinase 1/2 (pERK 1/2) were assessed using immunoblotting. LPC treatment reduced SOD1 levels but increased catalase levels...
  84. doi Deregulation of PERK in the autoimmune disease pemphigus vulgaris occurs via IgG-independent mechanisms
    A Lanza
    Dipartimento di Discipline Odontostomatologiche, Seconda Universita di Napoli, Naples, Italy
    Br J Dermatol 164:336-43. 2011
    ..We have shown previously that one of the earliest pathogenic events in PV is the activation of protein kinases, including the PKR-like endoplasmic reticulum (ER) kinase PERK.
  85. doi Treatment of ammonium-rich swine waste in modified porphyritic andesite fixed-bed anaerobic bioreactor
    Qinghong Wang
    Graduate School of Life and Environmental Science, University of Tsukuba, 1 1 1 Tennodai, Tsukuba, Ibaraki 305 8572, Japan
    Bioresour Technol 111:70-5. 2012
    In this study, a modified porphyritic andesite (WRS) was developed as ammonium adsorbent and bed material for the anaerobic digestion of ammonium-rich swine waste...
  86. doi Caspase-7 in molar tooth development
    E Matalova
    Institute of Animal Physiology and Genetics CAS, v v i, Brno, Czech Republic
    Arch Oral Biol 57:1474-81. 2012
    The primary enamel knot (PEK) is a population of cells that shows spatio-temporal restricted apoptosis during tooth development...
  87. doi Endoplasmic reticulum stress and protein quality control in diabetic cardiomyopathy
    Lifang Yang
    Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi an 710032, China Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071, USA
    Biochim Biophys Acta 1852:209-18. 2015
    ..major transmembrane proteins, including inositol-requiring enzyme 1 (IRE1), protein kinase RNA-like ER kinase (PERK), and activating transcription factor (ATF) 6...
  88. doi Neural mechanism underlying hyperalgesic response to orofacial pain in Parkinson's disease model rats
    Hiroharu Maegawa
    Department of Dental Anesthesiology, Osaka University Graduate School of Dentistry, Suita, Osaka 565 0871, Japan Electronic address
    Neurosci Res 96:59-68. 2015
    ..We also examined expression of c-Fos and phosphorylated extracellular signal-regulated kinase (pERK) in the trigeminal spinal subnucleus caudalis (Vc) and expression of c-Fos in the periaqueductal gray matter (PAG)...
  89. doi Cell death induced by endoplasmic reticulum stress
    Raffaella Iurlaro
    Cell Death Regulation Group, Bellvitge Biomedical Research Institute IDIBELL, L Hospitalet de Llobregat, Spain
    FEBS J 283:2640-52. 2016
    ..Central to the unfolded protein response are the sensors PERK, IRE1 and ATF6, as well as other signaling nodes such as c-Jun N-terminal kinase 1 (JNK) and the downstream ..
  90. pmc TFEB and TFE3 are novel components of the integrated stress response
    Jose A Martina
    Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
    EMBO J 35:479-95. 2016
    ..Treatment with ER stressors causes translocation of TFEB and TFE3 to the nucleus in a process that is dependent on PERK and calcineurin but not on mTORC1...
  91. pmc Icariin displays anticancer activity against human esophageal cancer cells via regulating endoplasmic reticulum stress-mediated apoptotic signaling
    Chongxi Fan
    Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi an 710038, China
    Sci Rep 6:21145. 2016
    ..Furthermore, ICA treatments upregulated the levels of ERS-related molecules (p-PERK, GRP78, ATF4, p-eIF2α, and CHOP) and a pro-apoptotic protein (PUMA) and simultaneously downregulated an anti-..
  92. ncbi Critical role of regulator of calcineurin 1 in spinal cord injury
    Guodong Wang
    Department of Orthopedics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People s Republic of China
    J Physiol Biochem 72:605-613. 2016
    ..protein 78 (GRP78) and phosphorylation of protein kinase RNA-like endoplasmic reticulum (ER) kinase (PERK) in rats with SCI were inhibited by LVshRNAi-RCAN1...
  93. doi ERK activated by Histamine H1 receptor is anti-proliferative through spatial restriction in the cytosol
    Ruchi Jain
    Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India
    Eur J Cell Biol 95:623-634. 2016
    ..activation through PLCβ, Src, PKCδ and MEK pathway, but does not lead to nuclear relocalization of phospho-ERK (pERK), classically associated with pro-proliferative changes...
  94. ncbi Phosphorylation of extracellular signal-regulated kinase in primary afferent neurons by noxious stimuli and its involvement in peripheral sensitization
    Yi Dai
    Department of Anatomy and Neuroscience, Hyogo College of Medicine, Hyogo 663 8501, Japan
    J Neurosci 22:7737-45. 2002
    ..We demonstrated that very rapid phosphorylation of extracellular signal-regulated protein kinases (pERK) occurred in DRG neurons that were taking part in the transmission of various noxious signals...
  95. ncbi Intramolecular dephosphorylation of ERK by MKP3
    YoungJoo Kim
    Oregon Health and Science University, Department of Biochemistry and Molecular Biology, Portland, Oregon 97239 3098, USA
    Biochemistry 42:15197-207. 2003
    ..we address the function of the N-terminal domain of MKP3 in either inter- or intramolecular dephosphorylation of pERK (phosphorylated ERK) and the stoichiometry of the MKP3/pERK Michaelis complex...
  96. ncbi Different effects of opioid and cannabinoid receptor agonists on C-fiber-induced extracellular signal-regulated kinase activation in dorsal horn neurons in normal and spinal nerve-ligated rats
    Yasuhiko Kawasaki
    Pain Research Center, Department of Anesthesiology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Pharmacol Exp Ther 316:601-7. 2006
    ..In this study, we examined whether opioids and cannabinoids can affect C-fiber-induced ERK phosphorylation (pERK) in dorsal horn neurons in spinal cord slices from normal and spinal nerve-ligated rats...
  97. ncbi ER stress (PERK/eIF2alpha phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation
    Y Kouroku
    Division of Development, National Institute of Neuroscience, 4 1 1 Ogawahigashi machi, Kodaira, Tokyo 187 8502, Japan
    Cell Death Differ 14:230-9. 2007
    ..2 alpha (eIF2alpha) A/A mutation, a knock-in to replace a phosphorylatable Ser51 with Ala51, and dominant-negative PERK inhibited polyQ72-induced LC3 conversion...
  98. ncbi The eIF2alpha kinases inhibit vesicular stomatitis virus replication independently of eIF2alpha phosphorylation
    Jothilatha Krishnamoorthy
    Lady Davis Institute for Medical Research, McGill University, Sir Mortimer B Davis Jewish General Hospital, Montreal, Quebec, Canada
    Cell Cycle 7:2346-51. 2008
    ..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...
  99. pmc Role of the host cell's unfolded protein response in arenavirus infection
    Giulia Pasqual
    Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne CH 1011, Switzerland
    J Virol 85:1662-70. 2011
    ..and interacts with three mediators: kinase/endonuclease inositol-requiring protein 1 (IRE1), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6)...
  100. pmc Perk-dependent repression of miR-106b-25 cluster is required for ER stress-induced apoptosis
    S Gupta
    School of Medicine Pathology, Clinical Science Institute, National University of Ireland Galway, Galway, Ireland
    Cell Death Dis 3:e333. 2012
    Activation of the unfolded protein response sensor PKR-like endoplasmic reticulum kinase (Perk) attenuates endoplasmic reticulum (ER) stress levels...
  101. doi Akt inactivation induces endoplasmic reticulum stress-independent autophagy in fibroblasts from patients with Pompe disease
    Yurika Nishiyama
    Department of Gene Therapy, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo 105 8461, Japan
    Mol Genet Metab 107:490-5. 2012
    ..as evidenced by increased levels of LC3-II and autophagic vesicles was observed in patient fibroblasts, whereas PERK phosphorylation reflecting the presence of ER stress was not observed in them...

Research Grants74

  1. Human Tryptophanyl-tRNA Synthetase-A Functional Analysis
    Jerry Johnson; Fiscal Year: 2006
    ..The tryptophan specific enzyme (WRS) from mammals is unique in that it is also an autophosphorylating protein kinase...
  2. MELANOMA CELL SURFACE PROTEOGLYCANS IN METASTASIS
    James B McCarthy; Fiscal Year: 2010
    ..of the ERK/MAPK pathway, including BRAF (which is mutated to the V600E active form in these cells), pMEK and pERK all precipitated with a GST-MCSP cytoplasmic tail fusion protein, while a truncated fusion protein lacking the c-..
  3. Randal J Kaufman; Fiscal Year: 2014
    ..A subpathway of the UPR is signaled through activation of the ER kinase PERK and phosphorylation of eukaryotic translation initiation factor 2 on the alpha subunit to transiently attenuate ..
  4. Constantinos Koumenis; Fiscal Year: 2016
    ..We have previously shown that hypoxic stress activates the endoplasmic reticulum (ER) kinase PERK thereby inducing phosphorylation of the translation initiation factor eIF2? on ser51...
  5. Translational Machinery in Stress Signaling and Tumor Suppression
    THOMAS J contact BEGLEY; Fiscal Year: 2010
    ..linked to activation of an ER stress response characterized by attenuation of translation initiation dependent on PERK and eIF2? phosphorylation4...
  6. Elucidating the role of the eIF2alpha kinase PERK in synaptic plasticity and memo
    MY AI TRINH; Fiscal Year: 2010
    ..to determine the specific role that the RNA-dependent protein kinase-like endoplasmic reticulum (ER) elF2a kinase (PERK) plays in regulating translation during these processes...
  7. Drug-like small molecule modulators of the Integrated Stress Response
    David Ron; Fiscal Year: 2010
    ..goals we will develop high throughput screens (HTS) for compounds that inhibit the ER stress inducible elF2a kinase PERK and secondary screens to evaluate the potency, specificity, bioavailability and off-target effects of the compounds...
  8. Tracy G Anthony; Fiscal Year: 2015
    ..endoplasmic reticulum (ER) stress, leading to induction of another eIF2 kinase called PKR-like ER- resident Kinase (PERK)...
  9. Makoto Miyazaki; Fiscal Year: 2016
    ..such as inorganic phosphate, inflammatory cytokines (TNFa) and saturated fatty acids through the activation of the PERK-elF2a axis of the UPR in vascular smooth muscle cells (VSMCs);2) adenovirus-mediated overexpression of ATF4 induced ..
  10. Bertal H Aktas; Fiscal Year: 2015
    ..Translation initiation is inhibited through activation of protein kinase R (PKR)-like ER resident kinase PERK and phosphorylation of eukaryotic translation initiation factor 2 aplha (eIF2a)...
  11. John D Bartlett; Fiscal Year: 2016
    ..stress, eIF2a can be phosphorylated by any one of four different kinases -- Gcn2 (Eif2ak4), Hri (Eif2ak1), Perk (Eif2ak3), and Pkr (Eif2ak2) - each of which responds to different stress stimuli...
  12. James D Lechleiter; Fiscal Year: 2014
    ..We discovered that the Ca2+ dependent phosphatase calcineurin (CN) can bind to PERK, a stress sensor in the endoplasmic reticulum (ER), increases its auto-phosphorylation and enhance a cellular ..
  13. BRIAN J POPKO; Fiscal Year: 2016
    ..The ER stress response activates the pancreatic ER kinase (PERK), which phosphorylates the eukaryotic translation initiation factor 2[unreadable] and specifically maintains client ..
  14. Qinghua Sun; Fiscal Year: 2015
    ..Fat tissues will also be assessed for PERK-mediated UPR pathway on mitochondrial function, inflammation and apoptosis. PM2.5 with Nickel or PM2...
  15. Matthew M Lavail; Fiscal Year: 2014
    ..We found that three parallel branches of the UPR, governed by IRE1, ATF6 and PERK, behave significantly differently in time course and that these differences in the duration of their signaling may ..
  16. Maria Almira Correia; Fiscal Year: 2016
    ..Moreover, such global alterations of hepatic P450 turnover would also rationalize the impaired drug clearance clinically observed in porphyric patients. ..
  17. Makoto Miyazaki; Fiscal Year: 2016
    ..synthesized by SCD in the endoplasmic reticulum induces vascular osteogenesis and calcification by activating the PERK-eIF2[unreadable]-ATF4-CHOP pathway of the unfolded protein response in vivo...
  18. Raghu Vemuganti; Fiscal Year: 2014
    ..1) What is the role of PERK-mediated ER stress pathway after TBI? (2) In the post-injury brain, are ER stress and oxidative stress connected? ..
  19. Wensheng Lin; Fiscal Year: 2015
    ..Activation of the pancreatic endoplasmic reticulum kinase (PERK) branch of the UPR inhibits global protein biosynthesis, but stimulates the expression of certain stress-induced ..
  20. Reactive Oxygen Species Signaling in the Hippocampus
    Eric Klann; Fiscal Year: 2012
    ..oxidase, 3) determine whether A[unreadable]-induced blockade of LTP requires eIF2[unreadable] phosphorylation via PERK, and 4) determine whether genetic reduction of eIF2[unreadable] phosphorylation prevents impairments in hippocampal ..
  21. Signaling Cell Death from the Endoplasmic Reticulum
    Scott A Oakes; Fiscal Year: 2013
    ..Major effectors of the UPR in mammalian cells are the ER-resident transmembrane sensors IRE11, PERK, and AFT6...
  22. HTP chemical genomic screens to identify positive regulators of the Unfolded Prot
    Randal J Kaufman; Fiscal Year: 2010
    ..with an accumulation of mis-folded or poorly secreted proteins;and 2) Specific and robust activation of the PERK-eIF21-CHOP (apoptotic) arm will exacerbate the UPR and lead to cell death in malignant cells with hyper-active ..
  23. Lauren D Stutzbach; Fiscal Year: 2014
    ..This gene codes for PERK, an endoplasmic reticulum (ER) membrane protein that functions as a sensor of mis- or unfolded proteins within the ..
  24. METABOLIC REGULATION IN THE ACUTE PHASE
    HYUNG D RYOO; Fiscal Year: 2010
    ..To define the role of PERK signaling in survival or death of ER stressed cells by utilizing conditionally active forms of PERK that are ..
  25. Janis L Abkowitz; Fiscal Year: 2015
    ..We can thus determine whether these different lineages share regulatory pathways. Together these studies should provide significant insights into heme signaling and toxicities during hematopoietic cell differentiation. ..
  26. Scott R Whittemore; Fiscal Year: 2015
    ..The 3 pathways involved in the ERSR involve PERK, IRE1/XBP-1, and ATF6 signaling. Preliminary data demonstrate upregulation of all 3 ERSR pathways following SCI...
  27. Synucleins: Cell biology and transgenic mice
    Michael K Lee; Fiscal Year: 2012
    ..With these issues in mind, we will use series of mutant mouse models targeting the Perk/eIF2alpha arm of the ER stress response to establish importance of ER stress response in neurodegeneration ..
  28. Randal J Kaufman; Fiscal Year: 2016
    ..Upon accumulation of unfolded proteins in the lumen of the ER, PERK, IREIa, and ATF6a are activated to increase the capacity of the ER to meet the demand for increased protein folding ..
  29. HRI/elF2aP Signaling Pathway as Potential Pharmaceutical Targets for Thalassemia
    Jane Jane Chen; Fiscal Year: 2010
    ..This study may also lead to the discovery of novel drug treatments for red blood cell diseases. ..
  30. HRI-eIF2a Phosphorylation Signaling in Oxidative Stress and Erythropoiesis
    Jane Jane Chen; Fiscal Year: 2013
    ....
  31. Proteasome Inhibition and ER Stress
    David J McConkey; Fiscal Year: 2013
    ..We will test the hypothesis that PIs inhibit PERK activation by inducing the expression of a molecular chaparone (HSP70?) that blocks PERK homoaggregation in drug-..
  32. Pharmacological targeting of the Unfolded Protein Response as an antitumor strate
    Constantinos Koumenis; Fiscal Year: 2012
    ..The PERK/eIF2a/ATF4 pathway reduces the global rates of protein translation thereby alleviating metabolic stress under ..
  33. Guanabenz in the treatment of mutant SOD1 ALS mice
    RAYMOND PHILIP ROOS; Fiscal Year: 2013
    ..We recently published data that show that haploinsufficiency of PERK (which as part of the unfolded protein response [UPR] leads to phosphorylation of eIF2[unreadable] with a ..
  34. James C Alwine; Fiscal Year: 2015
    ..activation of lipogenic genes have previously been shown to be mediated by PKR-like endoplasmic reticulum kinase (PERK), an ER-resident sensor that is activated by endoplasmic reticulum stress, specifically the unfolded protein ..
  35. Fatty acid synthase inhibitors and prostate cancer
    Steven J Kridel; Fiscal Year: 2010
    ..transformed mouse embryonic fibroblasts (MEFs) with pathway specific mutations to determine the contribution of the PERK, IRE1 and ATF6 signaling pathways to the ER stress response when FAS is inhibited...
  36. IDENTIFYING NOVEL MECHANISMS OF THERAPY RESISTANCE IN HNSCC
    APARNA RANGANATHAN SERTIL; Fiscal Year: 2011
    ..these dormant HEp3 (D-HEp3) cells also displayed a p38-dependent increases in the ER stress markers BiP/grp78 and PERK signaling...
  37. Douglas R Cavener; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): The focus of this proposal is to investigate the role of the PERK eIF2a kinase (EIF2AK3) in regulating proinsulin trafficking and quality control in the endoplasmic reticulum...
  38. Scott R Whittemore; Fiscal Year: 2015
    ..The ERSR has three arms initiated by PERK, IRE1, ATF6, respectively...
  39. Upper Airway Nerve Injury in Apnea: BIP-CHOP-SIRT1 Crosstalk
    Sigrid C Veasey; Fiscal Year: 2013
    ..First, susceptible motoneurons show activation of an endoplasmic reticulum (ER) sensor, PERK, in response to IH...
  40. MATRIX MEDIATORS OF WOUND HEALING
    Paul J Higgins; Fiscal Year: 2010
    ..USF, furthermore, formed transient complexes with pERK and interference with EGFR, ppSO0"5"1 or p160ROCK activity or ERK/p38 signaling ablated induced PAI-1 expression...
  41. Jane Jane Chen; Fiscal Year: 2016
    ..The outcome of this study may lead to the discovery of novel drug treatment for red blood cell diseases. ..
  42. Francis Young In Lee; Fiscal Year: 2015
    ..We will examine the functional interactions between pERK/cytokine expression and two diverging PTH signaling pathways (Gs/adenylate cyclase/cAMP and Gq/11-phospholipase C)...
  43. Interaction of cationic lipids with dendritic cells
    Leaf Huang; Fiscal Year: 2012
    ..b>pERK activation leads to the production and the secretion of potent chemokines, CCL2 and CCL4, by BMDC...
  44. Endoplasmic Reticulum Stress and Parkinson's Disease
    David Ron; Fiscal Year: 2004
    ..We will determine if in mice lacking the key UPR gene, PERK dopaminergic neurons are hypersensitive to 6-hydroxydopamine...
  45. Cannabinoids and Neuroimmune Interactions
    Edgar Alfonso Romero Sandoval; Fiscal Year: 2010
    ..The inhibition of pERK-1/2 results in a reduction of algesic factors, such as cy1okines, nitric oxide (NO) or prostaglandins...
  46. Ronald B Gartenhaus; Fiscal Year: 2015
    ..Blood 2011;PMID: 21628402). We showed that AZD6244 down-regulated pERK and key substrates including MCT-1, c-MYC and MCL-1...
  47. Sally E Wenzel; Fiscal Year: 2014
    ..In Aim 2, we will address the mechanisms by which the 15 LO1/15 HETE-PE pathway interacts with the pERK pathway to modulate gene expression...
  48. High Throughput Chemical Genomic screening to identify novel ER stress-inducing
    ANDREW MICHAEL FRIBLEY; Fiscal Year: 2010
    ..developed a complementary cellbased assay using stably transfected CHO-K1 cells that individually report on the PERK/elF2o/CHOP (apoptotic) and the IRE1/XBP1 (adaptive) pathways of the UPR...
  49. Genomic screening to identify novel stress-inducing chemotherapies for carcinoma
    ANDREW MICHAEL FRIBLEY; Fiscal Year: 2013
    ..developed a Complementary cell-based assay using stably transfected CMQ-K1 cells that individually report on the PERK/elF2D/CH0P (apoptotic) and the IRE1/XBP1 (adaptive) pathways of the UPR...
  50. INHIBITION OF TRANSLATION INITIATION IN CANCER THERAPY
    Jose Halperin; Fiscal Year: 2005
    ..We will also evaluate the relative role of the two ER-resident eIF2 kinases, PKR and PERK, and of the ER-stress gene CHOP, as the downstream effectors of Ca-depleting TI inhibitors...
  51. Alcohol-Induced Regulation of Hepatic Protein Synthesis
    THOMAS VARY; Fiscal Year: 2007
    ..Ethanol or its metabolites may cause a selective activation of 1 of the known elF2 kinases (PERK, GCN2, PKR or HRI) or inhibit elF2a phosphatase activity...
  52. Radiosensitization of Breast Cancer Cells by Vitamin D3 and Vitamin D Analogs
    Eden Wilson; Fiscal Year: 2012
    ..of EB /1,25 D3 and radiation on the levels of crucial mediators involved in the ER stress (elF2a, JNK and XBP-1, PERK, IRE-1) and mTOR (4EBP-1 &S6k1) pathways in MCF-7, MCF-7 Her-2/neu and SKBR3 cells by western blot analysis...
  53. Screening for Inhibitors of the Integrated Stress Response
    David Ron; Fiscal Year: 2007
    ..Phosphorylation of translation initiation factor 2a (eIF2a) by the ER stress activated protein kinase PERK is a well understood and potentially malleable arm of the UPR that is referred to as the integrated stress response ..
  54. Serotonin Reuptake Inhibitors and 5-HT1A Receptors
    George Battaglia; Fiscal Year: 2009
    ..agonist activation of MAP kinase in the hypothalamic PVN and the localization of 5-HT1A activated MAP kinase (pERK) to oxytocin- and CRF-positive neurons;Aim 3 will determine the mechanisms by which serotonin/norepinephrine ..
  55. Activation of the Trigeminovascular Pathway
    Rami Burstein; Fiscal Year: 2011
    ..In Specific Aim 1/>, we will test the effect of CSD on dural expression of pERK, a surrogate marker for nociceptive activation...
  56. Norbert E Kaminski; Fiscal Year: 2016
    ..secreting cells, TCDD- treatment caused elevated and sustained levels of BCL6, and decreased levels of CD80, CD69, pERK, p- p65/NF?B, and p-cJun, which are hallmarks of impaired B cell activation...
  57. Constantinos Koumenis; Fiscal Year: 2016
    ..The UPR and specifically the PERK kinase, has recently been shown to facilitate oncogene-mediated tumor progression, suggesting that the UPR may also ..
  58. William E Armstrong; Fiscal Year: 2016
    ..Specific Aim 2. To test whether OT's effects on AHPs are mediated through a pERK 1/2-MAPK cascade, and whether it is associated with an increase expression of the AHP channels and/or the enzymes ..
  59. MARK ANDREW LAWSON; Fiscal Year: 2014
    ..We are investigating the mechanisms cells use to adapt to stress and preserve normal cell function. These regulatory pathways are essential to assure proper reproductive hormone synthesis and reproductive success. ..
  60. Marc B Schenker; Fiscal Year: 2016
    ..Physiological, cultural and work place information collected in the fields will define vulnerability to HRI and allow us to devise prevention strategies meaningful to the overwhelmingly Latino workforce. ..
  61. ANDREW MARK STRASSMAN; Fiscal Year: 2014
    ..Complementary studies will be carried out to examine anatomical markers of neural activation (fos and pERK) to correlate activation in superficial or deep dorsal horn laminae, as well as other central regions, with the ..
  62. Role of GPR30 in Mediating Estrogen Effects on Neurons and Cognitive Performance
    REBECCA L HAMMOND; Fiscal Year: 2012
    ..1997;Levin, 2005). Our studies will evaluate rapid induction of pCREB and pERK within cholinergic neurons in response to systemic and intracerebroventricular infusions of G-1and other ER ..
  63. Barry T Hinton; Fiscal Year: 2016
    ..that the switch between the FGF/FGFR/ PI3K/Akt/mTOR pathway, which is required for cell proliferation, toFGF/FGFR/pERK/pMEK pathway, which is required for cell protection is the result of PTEN upregulation, activation and/or ..
  64. M Celeste Simon; Fiscal Year: 2016
    ..Experiments proposed in Project 3 are based on the hypothesis that PERK (as a sensor of cellular nutrient availability) functions as a critical pro-survival factor via activation of a ..
  65. VALERIE VI THIEN MAC; Fiscal Year: 2016
    ..Results from this study will also expand HRI knowledge and contribute to interventions for other vulnerable working populations. ..
  66. CHARLES F GROSE; Fiscal Year: 2015
    ..experimental approach directed toward the three sensor pathways that lead from ER stress to the UPR (IRE1, ATF6 and PERK)...
  67. Diagnosing Emergence of Kinase Inhibitor Resistance on a Microchip
    Thomas G Graeber; Fiscal Year: 2013
    ..Namely, the platform will monitor pERK, PDGFR[unreadable], pAKT and the apoptosis reporter cleaved Caspase-3/7 using fine needle aspirate (FNA) biopsies...
  68. The Unfolded Protein Response After Brain Ischemia
    DONALD DEGRACIA; Fiscal Year: 2006
    ..Moreover, the kinase that phosphorylates eIF2alpha immediately after brain ischemia and reperfusion, PERK, is known to be activated only by the endoplasmic reticulum stress signaling system termed the unfolded protein ..
  69. Unfolded Protein Response in Glucose Homeostasis
    Randal Kaufman; Fiscal Year: 2006
    ..In addition, protein synthesis is transiently attenuated through PERK-mediated phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2()...
  70. The Unfolded Protein Response in Subjects with COPD
    Steven Kelsen; Fiscal Year: 2009
    ..We also found that cigarette smoke specifically activates the UPR-sensor, PERK (protein kinase R-like ER resident kinase) and its signaling pathway which up-regulates expression of the master ..
  71. REGULATION OF PROTEIN SYNTHESIS AND ERYTHROPOIESIS
    Jane Jane Chen; Fiscal Year: 2007
    ..HRI is also important for the survival of mice with thalassemia and erythropoietic protoporphria. Our proposed study may lead to potential application of HRI in treating human patients with red cell diseases. ..
  72. Nitric oxide mimetic NSAIDs for treatment of Alzheimer's Disease
    GREGORY THATCHER; Fiscal Year: 2007
    ..Aim 2: to assay drugs in hippocampal slice cultures, measuring by immunoblot, markers of cognition enhancement (pERK, pCREB) and inflammation (iNOS, MHC-II)...
  73. METABOLIC REGULATION IN THE ACUTE PHASE
    David Ron; Fiscal Year: 2002
    ..The second, Perk, plays a role in attenuating translation in response to the accumulation of unfolded proteins in the ER and as such ..
  74. Colon Cancer Risk Modification by PPI and HRI Therapy
    Yu Xiao Yang; Fiscal Year: 2007
    ..This award will enable the candidate to complete the development of the skills and experience necessary to evolve into an independent academic investigator. ..