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
Products:     PERK

Top Publications

  1. Shi Y, Vattem K, Sood R, An J, Liang J, Stramm L, et al. Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control. Mol Cell Biol. 1998;18:7499-509 pubmed
    ..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 ..
  2. Senée V, Vattem K, Delepine M, Rainbow L, Haton C, Lecoq A, et al. Wolcott-Rallison Syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity. Diabetes. 2004;53:1876-83 pubmed
    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 ..
  3. Ozbek M, Senée V, Aydemir S, Kotan L, Mungan N, Yuksel B, et al. Wolcott-Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature. Pediatr Diabetes. 2010;11:279-85 pubmed publisher
    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...
  4. Sang Y, Liu M, Yang W, Yan J, Chengzhu -, Ni G. A novel EIF2AK3 mutation leading to Wolcott-Rallison syndrome in a Chinese child. J Pediatr Endocrinol Metab. 2011;24:181-4 pubmed
    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...
  5. 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
    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...
  6. Ma K, Vattem K, Wek R. Dimerization and release of molecular chaperone inhibition facilitate activation of eukaryotic initiation factor-2 kinase in response to endoplasmic reticulum stress. J Biol Chem. 2002;277:18728-35 pubmed
    ..This study addresses the mechanisms activating PEK, also designated PERK or EIF2AK3...
  7. Okada T, Yoshida H, Akazawa R, Negishi M, Mori K. 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. Biochem J. 2002;366:585-94 pubmed
    ..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 ..
  8. 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...
  9. Kim K, Pae H, Zheng M, Park R, Kim Y, Chung H. 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. Circ Res. 2007;101:919-27 pubmed
    ..exogenous CO activated Nrf2 through the phosphorylation of protein kinase R-like endoplasmic reticulum kinase (PERK), resulting in HO-1 expression...

More Information

Publications105 found, 100 shown here

  1. Lu W, László C, Miao Z, Chen H, Wu S. The role of nitric-oxide synthase in the regulation of UVB light-induced phosphorylation of the alpha subunit of eukaryotic initiation factor 2. J Biol Chem. 2009;284:24281-8 pubmed publisher
    ..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 ..
  2. Lee D, Lee K, Lee H, Kim D, Noh Y, Yu K, et al. Activation of PERK signaling attenuates Abeta-mediated ER stress. PLoS ONE. 2010;5:e10489 pubmed publisher
    ..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...
  3. Reis A, Kannengiesser C, Jennane F, Manna T, Cheurfa N, Oudin C, et al. Two novel mutations in the EIF2AK3 gene in children with Wolcott-Rallison syndrome. Pediatr Diabetes. 2011;12:187-91 pubmed publisher
    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...
  4. 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 ..
  5. Koumenis C, Naczki C, Koritzinsky M, Rastani S, Diehl A, Sonenberg N, et al. Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha. Mol Cell Biol. 2002;22:7405-16 pubmed
    ..The endoplasmic reticulum (ER)-resident eIF2alpha kinase PERK was hyperphosphorylated upon hypoxic stress, and overexpression of wild-type PERK increased the levels of hypoxia-..
  6. Park M, Curiel D, Koumenis C, Graf M, Chen C, Fisher P, et al. PERK-dependent regulation of HSP70 expression and the regulation of autophagy. Autophagy. 2008;4:364-7 pubmed
    ..It notes that in PKR-like endoplasmic reticulum kinase null cells (PERK-/-) the lethality of OSU is attenuated...
  7. Biason Lauber A, Lang Muritano M, Vaccaro T, Schoenle E. Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene. Diabetes. 2002;51:2301-5 pubmed
    Wolcott-Rallison syndrome (WRS) is an autosomal recessive disorder characterized by neonatal or early infancy type 1 diabetes, epiphyseal dysplasia, and growth retardation...
  8. 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...
  9. Bi M, Naczki C, Koritzinsky M, Fels D, Blais J, Hu N, et al. ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth. EMBO J. 2005;24:3470-81 pubmed
    ..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 ..
  10. 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 ..
  11. Rubio Cabezas O, Patch A, Minton J, Flanagan S, Edghill E, Hussain K, et al. Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families. J Clin Endocrinol Metab. 2009;94:4162-70 pubmed publisher
    Mutations in EIF2AK3 cause Wolcott-Rallison syndrome (WRS), a rare recessive disorder characterized by early-onset diabetes, skeletal abnormalities, and liver dysfunction...
  12. Höglinger G, Melhem N, Dickson D, Sleiman P, Wang L, Klei L, et al. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat Genet. 2011;43:699-705 pubmed publisher
    ..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. ..
  13. Cao J, Dai D, Yao L, Yu H, Ning B, Zhang Q, et al. Saturated fatty acid induction of endoplasmic reticulum stress and apoptosis in human liver cells via the PERK/ATF4/CHOP signaling pathway. Mol Cell Biochem. 2012;364:115-29 pubmed publisher
    ..Silence of PRK-like ER kinase (PERK) expression in liver cells was through transient transfection of PERK shRNA...
  14. Avivar Valderas A, Bobrovnikova Marjon E, Alan Diehl J, Bardeesy N, Debnath J, Aguirre Ghiso J. Regulation of autophagy during ECM detachment is linked to a selective inhibition of mTORC1 by PERK. Oncogene. 2013;32:4932-40 pubmed publisher
    ..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 ..
  15. Liu J, Hoppman N, O Connell J, Wang H, Streeten E, McLenithan J, et al. A functional haplotype in EIF2AK3, an ER stress sensor, is associated with lower bone mineral density. J Bone Miner Res. 2012;27:331-41 pubmed publisher
    ..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. ..
  16. Engin A. Human Protein Kinases and Obesity. Adv Exp Med Biol. 2017;960:111-134 pubmed publisher
    ..protein response stress sensors, RNA-dependent protein kinase-like ER eukaryotic initiation factor-2alpha kinase (PERK) and activating transcription factor-6...
  17. Yun S, Han Y, Lee J, Kim S, Lee S. Enhanced Susceptibility to 5-Fluorouracil in Human Colon Cancer Cells by Silencing of GRP78. Anticancer Res. 2017;37:2975-2984 pubmed
    ..levels of ER stress marker proteins, such as phosphorylated protein kinase-like endoplasmic reticulum kinase (PERK), phosphorylated eukaryotic initiation factor 2 alpha (eIF2?), activating transcription factor 4 (ATF4), ..
  18. Mazzio E, Lewis C, Soliman K. Transcriptomic Profiling of MDA-MB-231 Cells Exposed to Boswellia Serrata and 3-O-Acetyl-B-Boswellic Acid; ER/UPR Mediated Programmed Cell Death. Cancer Genomics Proteomics. 2017;14:409-425 pubmed
    ..Bio-statistical analysis demarcates the primary effect of both BSE/3-OA?BA on the up-regulation of PERK (protein kinase RNA-like endoplasmic reticulum kinase)- endoplasmic reticulum (ER)/unfolded protein response (UPR) ..
  19. Lugea A, Gerloff A, Su H, Xu Z, Go A, Hu C, et al. The Combination of Alcohol and Cigarette Smoke Induces Endoplasmic Reticulum Stress and Cell Death in Pancreatic Acinar Cells. Gastroenterology. 2017;153:1674-1686 pubmed publisher
    ..AR42J cells, but induced oxidative stress and sustained activation (phosphorylation) of eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3, also called PERK) and increased protein levels of DNA damage inducible ..
  20. Baer A, Lundberg L, Swales D, Waybright N, Pinkham C, Dinman J, et al. Venezuelan Equine Encephalitis Virus Induces Apoptosis through the Unfolded Protein Response Activation of EGR1. J Virol. 2016;90:3558-72 pubmed publisher
    ..The protein kinase RNA-like endoplasmic reticulum kinase (PERK) arm of the UPR was activated, as the expression of both activating transcription factor 4 (ATF4) and CHOP (DDIT3), ..
  21. Phillipson Weiner L, Mirek E, Wang Y, McAuliffe W, Wek R, Anthony T. General control nonderepressible 2 deletion predisposes to asparaginase-associated pancreatitis in mice. Am J Physiol Gastrointest Liver Physiol. 2016;310:G1061-70 pubmed publisher
    ..GCN2 in a pancreas exposed to asparaginase induced ER stress, phosphorylation of protein kinase R-like ER kinase (PERK) and its substrate eIF2 was increased in the pancreas of asparaginase-treated ?Gcn2 mice...
  22. Zhao Y, Gao Y, Wu X, Wang J, Duan L. [Protective effect of earthworm active ingredients against endoplasmic reticulum stress-induced acute liver injury in mice]. Zhongguo Zhong Yao Za Zhi. 2017;42:1183-1188 pubmed publisher
    ..expressions of ERS related proteins, including glucose regulated protein 78(GRP78), protein kinase R-like ER kinase(PERK), eukaryotic transcription initiation factor 2?(eIF2?), active transcription factor-4(ATF4) and CCAAT/enhancer ..
  23. Villalobos Labra R, Sáez P, Subiabre M, Silva L, Toledo F, Westermeier F, et al. Pre-pregnancy maternal obesity associates with endoplasmic reticulum stress in human umbilical vein endothelium. Biochim Biophys Acta Mol Basis Dis. 2018;: pubmed publisher
    ..the expression and activation of the ER stress sensors protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1? (IRE1?), and activating transcription factor 6 (ATF6)...
  24. Zhang W, Sun Z, Meng F. Schisandrin B Ameliorates Myocardial Ischemia/Reperfusion Injury Through Attenuation of Endoplasmic Reticulum Stress-Induced Apoptosis. Inflammation. 2017;40:1903-1911 pubmed publisher
    ..such as C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6), and (PKR)-like ER kinase (PERK) were further measured by western blot, and their messenger RNA levels were measured by real-time PCR...
  25. Kahali S, Sarcar B, Fang B, Williams E, Koomen J, Tofilon P, et al. Activation of the unfolded protein response contributes toward the antitumor activity of vorinostat. Neoplasia. 2010;12:80-6 pubmed
    ..activation of its client protein double-stranded RNA-activated protein-like endoplasmic reticulum kinase (PERK)...
  26. Booth L, Roberts J, Sander C, Lee J, Kirkwood J, Poklepovic A, et al. The HDAC inhibitor AR42 interacts with pazopanib to kill trametinib/dabrafenib-resistant melanoma cells in vitro and in vivo. Oncotarget. 2017;8:16367-16386 pubmed publisher
    ..Knock down of PERK, eIF2?, Beclin1, ATG5 or AMPK?, or expression of I?B S32A S36A, ca-mTOR or TRX, reduced cell killing...
  27. Stan R, Silva R, de Camargo M. Human GRP78 affinity towards its signaling partners Ire1? and PERK is differently modulated by an unfolded protein client. Biochem Biophys Res Commun. 2017;487:375-380 pubmed publisher
    ..affinities between human GRP78, an essential chaperone located in ER, and two transmembrane UPR sensors (human PERK and Ire1?), with or without the addition of an unfolded protein client...
  28. Wen Y, Zhu Y. [Construction of a lentiviral vector of RNA interference of PERK gene and identification in human dental pulp cells]. Shanghai Kou Qiang Yi Xue. 2017;26:363-367 pubmed
    To construct an expression vector of a small hairpin RNA (shRNA) targeting human PERK gene and to observe gene-silencing effects of PERK in human dental pulp cells (DPCs).
  29. Tsukumo Y, Tsukahara S, Furuno A, Iemura S, Natsume T, Tomida A. TBL2 Associates With ATF4 mRNA Via Its WD40 Domain and Regulates Its Translation During ER Stress. J Cell Biochem. 2016;117:500-9 pubmed publisher
    PKR-like ER-resident kinase (PERK) phosphorylates eukaryotic translation initiation factor 2 α (eIF2α) under endoplasmic reticulum (ER) stress; this results in repression of general translation and induction of specific gene ..
  30. Rizvi S, Parveen A, Ahmad I, Ahmad I, Verma A, Arshad M, et al. Aluminum Activates PERK-EIF2α Signaling and Inflammatory Proteins in Human Neuroblastoma SH-SY5Y Cells. Biol Trace Elem Res. 2016;172:108-19 pubmed publisher
    ..It was observed that aluminum potentially enhanced protein levels of PERK, EIF2α, caspase 9, caspase 3, and inflammatory markers like NF-κB, NLRP3, HMGB1, and nitric oxide (NO)...
  31. Lumley E, Osborn A, Scott J, Scholl A, Mercado V, McMahan Y, et al. Moderate endoplasmic reticulum stress activates a PERK and p38-dependent apoptosis. Cell Stress Chaperones. 2017;22:43-54 pubmed publisher
    ..mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment...
  32. Dong Z, Zhou J, Zhang Y, Chen Y, Yang Z, Huang G, et al. Astragaloside-IV Alleviates Heat-Induced Inflammation by Inhibiting Endoplasmic Reticulum Stress and Autophagy. Cell Physiol Biochem. 2017;42:824-837 pubmed publisher
    ..AS IV alleviated heat-induced excessive autophagy in vitro and in vivo. Excessive autophagy was attenuated by the PERK inhibitor GSK2656157 and eIF2? siRNA, suggesting that heat stress-induced autophagy can activate the PERK-eIF2? ..
  33. Wang Y, Tu L, Li Y, Chen D, Liu Z, Hu X, et al. Notoginsenoside R1 Alleviates Oxygen-Glucose Deprivation/Reoxygenation Injury by Suppressing Endoplasmic Reticulum Calcium Release via PLC. Sci Rep. 2017;7:16226 pubmed publisher
    ..The results showed that NGR1 inhibited IICR and strengthened the binding of GRP78 with PERK and IRE1. NGR1 also alleviated the activation of the CaMKII pathway...
  34. da Rosa Couto R, Faversani J, Ceretta C, Ferreira P, Marchezan C, Basso Facco D, et al. Health risk assessment and soil and plant heavy metal and bromine contents in field plots after ten years of organic and mineral fertilization. Ecotoxicol Environ Saf. 2018;153:142-150 pubmed publisher
    ..The intake of corn and wheat fertilized with pig slurry manure, swine deep bed, liquid cattle manure and industrialized mineral fertilizer did not present TCR. ..
  35. Ochi N, Isozaki H, Takeyama M, Singer J, Yamane H, Honda Y, et al. Synergistic effect of pacritinib with erlotinib on JAK2-mediated resistance in epidermal gowth factor receptor mutation-positive non-small cell lung Cancer. Exp Cell Res. 2016;344:194-200 pubmed publisher
    ..The combination markedly suppressed pAKT and pERK although pSTAT3 expression was similar regardless of treatment with the pacritinib, pacritinib + erlotinib, or ..
  36. Huang Z, Chen R, Zhou X, Zhan H, Hu M, Liu B, et al. Long non-coding RNA MEG3 induces cell apoptosis in esophageal cancer through endoplasmic reticulum stress. Oncol Rep. 2017;37:3093-3099 pubmed publisher
    ..MEG3 overexpression increased the expression of ER stress?related proteins (GRP78, IRE1, PERK, ATF6, CHOP and cleaved?caspase-3). Our results first demonstrate that MEG3 is downregulated in ESCC tissues...
  37. Zou W, Bai Y, Wang X, Cheng K, Sun H, Zhang G, et al. PERK-Phosphorylated eIF2? Pathway Suppresses Tumor Metastasis Through Downregulating Expression of Programmed Death Ligand 1 and CXCL5 in Triple-Negative Breast Cancer. Cancer Biother Radiopharm. 2017;32:282-287 pubmed publisher
    ..PKR-like ER kinase-phosphorylated eukaryotic translation initiation factor 2? (PERK-p-eIF2?) pathway is one of the three main signal pathways in ER stress, however, its mechanism in regulating breast ..
  38. Tai W, Yong W, Lim C, Low L, Tham C, Koh T, et al. A phase Ib study of selumetinib (AZD6244, ARRY-142886) in combination with sorafenib in advanced hepatocellular carcinoma (HCC). Ann Oncol. 2016;27:2210-2215 pubmed publisher
    ..although associated with inhibition of tumour growth and angiogenesis in in vivo studies, leads to up-regulation of pERK. The addition of MEK inhibition could potentially abrogate this effect and potentiate anti-tumour activity...
  39. Fang P, Yu M, Min W, Han S, Shi M, Zhang Z, et al. Beneficial effect of baicalin on insulin sensitivity in adipocytes of diet-induced obese mice. Diabetes Res Clin Pract. 2018;139:262-271 pubmed publisher
    ..findings showed that administration of baicalin decreased food intake, body weight, HOMA-IR and p-p38 MAPK and pERK levels, but enhanced pAKT and PGC-1? contents, as well as GLUT4 mRNA, PGC-1? mRNA expression in adipocytes, and ..
  40. Li C, Fan Q, Quan H, Nie M, Luo Y, Wang L. The three branches of the unfolded protein response exhibit differential significance in breast cancer growth and stemness. Exp Cell Res. 2018;367:170-185 pubmed publisher
    ..namely inositol-requiring enzyme-1α (IRE1α), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) and activating transcription factor 6α (ATF6α)...
  41. Bolívar P, Mugal C, Nater A, Ellegren H. Recombination Rate Variation Modulates Gene Sequence Evolution Mainly via GC-Biased Gene Conversion, Not Hill-Robertson Interference, in an Avian System. Mol Biol Evol. 2016;33:216-27 pubmed publisher
    ..Analyses of the site-frequency spectrum showed that W-to-S mutations were skewed toward high, and S-to-W mutations toward low, frequencies, consistent with a prevalent gBGC-driven fixation bias. ..
  42. Bortnowska G, Krudos A, Schube V, Krawczyńska W, Krzemińska N, Mojka K. Effects of waxy rice and tapioca starches on the physicochemical and sensory properties of white sauces enriched with functional fibre. Food Chem. 2016;202:31-9 pubmed publisher
    ..the physicochemical and sensory properties of gluten-free white sauces (WSs) prepared with waxy rice starch (WRS) or tapioca starch (TS) and high amylose maize starch (HAMS) as the source of resistance starch RS2 type...
  43. Li Y, Tardif G, Hum D, Kapoor M, Fahmi H, Pelletier J, et al. The unfolded protein response genes in human osteoarthritic chondrocytes: PERK emerges as a potential therapeutic target. Arthritis Res Ther. 2016;18:172 pubmed publisher
    ..Several UPR genes, among them ERN1, PERK, and CREB3L2 were downregulated in OA compared to normal chondrocytes at both the mRNA and protein levels, but the ..
  44. Goto N, Morita Y, Terada K. Deposits from Creams Containing 20% (w/w) Urea and Suppression of Crystallization (Part 3): Novel Analytical Methods Based on Raman Spectroscopy for the Characterization of Deposits and Deposition Phenomena of Creams Containing 20% (w/w) Urea. Chem Pharm Bull (Tokyo). 2016;64:1099-107 pubmed publisher
    ..we demonstrate the usefulness of this new method, called application to glass-wide-field Raman spectroscopy (AG-WRS)...
  45. Gwak H, Kim S, Dhanasekaran D, Song Y. Resveratrol triggers ER stress-mediated apoptosis by disrupting N-linked glycosylation of proteins in ovarian cancer cells. Cancer Lett. 2016;371:347-53 pubmed publisher
    ..cellular apoptosis as indicated by the up-regulation of GADD153, followed by the activation of ER-stress sensors (PERK and ATF6α)...
  46. Cormenier J, Martin N, Deslé J, Salazar Cardozo C, Pourtier A, Abbadie C, et al. The ATF6? arm of the Unfolded Protein Response mediates replicative senescence in human fibroblasts through a COX2/prostaglandin E2 intracrine pathway. Mech Ageing Dev. 2018;170:82-91 pubmed publisher mediate cellular senescence in normal human fibroblasts, could be controlled by the UPR sensors ATF6?, IRE1? and PERK. We found that UPR inducers cause premature senescence through an increase in COX2 expression, and an ..
  47. Li J, Wang Y, Wang Y, Wen X, Ma X, Chen W, et al. Pharmacological activation of AMPK prevents Drp1-mediated mitochondrial fission and alleviates endoplasmic reticulum stress-associated endothelial dysfunction. J Mol Cell Cardiol. 2015;86:62-74 pubmed publisher enhancing dynamin-related protein 1 (Drp1) phosphorylation (Ser 637) and thereby attenuated IRE-1α and PERK phosphorylation, but their actions were blocked by knockdown of AMPK...
  48. Hurt A, Besselaar T, Daniels R, Ermetal B, Fry A, Gubareva L, et al. Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2014-2015. Antiviral Res. 2016;132:178-85 pubmed publisher
    ..9%), but similar to the 2012-13 period (0.6%). Based on the current analysis, the NAIs remain an appropriate choice for the treatment and prophylaxis of influenza virus infections. ..
  49. Ito T, Ozaki S, Chanasong R, Mizutani Y, Oyama T, Sakurai H, et al. Activation of ERK/IER3/PP2A-B56?-positive feedback loop in lung adenocarcinoma by allelic deletion of B56? gene. Oncol Rep. 2016;35:2635-42 pubmed publisher
    ..Phosphorylated ERK (pERK) was also overexpressed in almost all adenocarcinomas...
  50. Chang L, Hsieh M, Yang J, Lu C, Tsai F, Tsao J, et al. Effect of bis(hydroxymethyl) alkanoate curcuminoid derivative MTH-3 on cell cycle arrest, apoptotic and autophagic pathway in triple-negative breast adenocarcinoma MDA-MB-231 cells: An in vitro study. Int J Oncol. 2018;52:67-76 pubmed publisher
    ..MTH-3 also decreased the protein levels of Ero1, PDI, PERK and calnexin, as well as increased the expression of IRE1?, CHOP and Bip that consequently led to ER stress and MDA-..
  51. Jiang Z, Ma Y, Li M, Zhan X, Zhang X, Wang M. 5-Hydroxymethylfurfural protects against ER stress-induced apoptosis in GalN/TNF-α-injured L02 hepatocytes through regulating the PERK-eIF2α signaling pathway. Chin J Nat Med. 2015;13:896-905 pubmed publisher
    ..the disturbance of intracellular Ca(2+) concentration, the activation of protein kinase RNA (PKR)-like ER kinase (PERK), phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α), and expression of ATF4 and CHOP proteins, ..
  52. Nakaya Y, Tsuboi Y, Okada Ogawa A, Shinoda M, Kubo A, Chen J, et al. ERK-GluR1 phosphorylation in trigeminal spinal subnucleus caudalis neurons is involved in pain associated with dry tongue. Mol Pain. 2016;12: pubmed publisher
    ..These findings suggest that the pERK-pGluR1 cascade is involved in central sensitization of trigeminal spinal subnucleus caudalis nociceptive neurons, ..
  53. Soto Pantoja D, Wilson A, Clear K, Westwood B, Triozzi P, Cook K. Unfolded protein response signaling impacts macrophage polarity to modulate breast cancer cell clearance and melanoma immune checkpoint therapy responsiveness. Oncotarget. 2017;8:80545-80559 pubmed publisher
    The unfolded protein response (UPR) is a stress pathway controlled by GRP78 to mediate IRE1, PERK, and ATF6 signaling. We show that targeting GRP78, IRE1, and PERK differentially regulates macrophage polarization...
  54. Stockwell S, Platt G, Barrie S, Zoumpoulidou G, te Poele R, Aherne G, et al. Mechanism-based screen for G1/S checkpoint activators identifies a selective activator of EIF2AK3/PERK signalling. PLoS ONE. 2012;7:e28568 pubmed publisher
    ..initiation factor 2-alpha (EIF2A) through the eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3/PERK) as the mechanism of action of this compound...
  55. Wang M, Ye R, Barron E, Baumeister P, Mao C, Luo S, et al. Essential role of the unfolded protein response regulator GRP78/BiP in protection from neuronal apoptosis. Cell Death Differ. 2010;17:488-98 pubmed publisher
    ..Our studies uncover a novel link between GRP78 depletion and reduction in cytosolic ubiquitination and establish a novel mouse model of accelerated cerebellar degeneration with basic and clinical applications. ..
  56. Lu X, Qiao Y, Li Y, Yang B, Chen M, Xing C. Preclinical study of cinobufagin as a promising anti-colorectal cancer agent. Oncotarget. 2017;8:988-998 pubmed publisher
    ..reticulum stress (ER stress), the latter was evidenced by caspase-12 activation, CHOP expression, as well as PERK and IRE1 phosphorylations...
  57. Bernhart E, Kogelnik N, Prasch J, Gottschalk B, Goeritzer M, Depaoli M, et al. 2-Chlorohexadecanoic acid induces ER stress and mitochondrial dysfunction in brain microvascular endothelial cells. Redox Biol. 2018;15:441-451 pubmed publisher
    ..The protein kinase R-like ER kinase (PERK) inhibitor GSK2606414 suppressed 2-ClHA-mediated activating transcription factor 4 synthesis and IL-6/8 secretion, ..
  58. Liang Y, Chen J, Yu Q, Ji T, Zhang B, Xu J, et al. Phosphorylated ERK is a potential prognostic biomarker for Sorafenib response in hepatocellular carcinoma. Cancer Med. 2017;: pubmed publisher
    ..Previous study has demonstrated that phosphorylated ERK (pERK) is a key downstream component in the RAF/MEK/ERK signaling pathway...
  59. Cibella F, Cuttitta G, Romano S, Grassi B, Bonsignore G, Milic Emili J. Respiratory energetics during exercise at high altitude. J Appl Physiol (1985). 1999;86:1785-92 pubmed
    ..On the basis of simultaneous records of esophageal pressure and lung volume, the mechanical power of breathing (Wrs) was measured in four normal subjects during exercise at sea level (SL) and after a 1-mo sojourn at 5,050 m...
  60. Sun X, Liao W, Wang J, Wang P, Gao H, Wang M, et al. CSTMP induces apoptosis and mitochondrial dysfunction in human myeloma RPMI8226 cells via CHOP-dependent endoplasmic reticulum stress. Biomed Pharmacother. 2016;83:776-784 pubmed publisher
    ..CHOP, GRP78, GRP94 and cleaved caspase-12) and the activation of multiple branches of ER stress transducers (PERK-eIF2?, IRE1? and ATF6)...
  61. Ho Y, Li X, Jamison S, Harding H, McKinnon P, Ron D, et al. PERK Activation Promotes Medulloblastoma Tumorigenesis by Attenuating Premalignant Granule Cell Precursor Apoptosis. Am J Pathol. 2016;186:1939-1951 pubmed publisher
    Evidence suggests that activation of pancreatic endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic reticulum stress negatively or positively influences cell transformation by regulating apoptosis...
  62. Shimizu A, Kaira K, Yasuda M, Asao T, Ishikawa O. Clinical and Pathological Significance of ER Stress Marker (BiP/GRP78 and PERK) Expression in Malignant Melanoma. Pathol Oncol Res. 2017;23:111-116 pubmed publisher
    ..and tumor specimens were stained by immunohistochemistry for BiP/GRP78, PKR-like endoplasmic reticulum kinase (PERK), Ki-67, p53 and microvessel density (MVD) determined by CD34...
  63. Liu C, Yan D, Tan X, Ma Z, Wang C, Deng Y, et al. Effect of the cross-talk between autophagy and endoplasmic reticulum stress on Mn-induced alpha-synuclein oligomerization. Environ Toxicol. 2017;: pubmed publisher
    ..3-MA pretreatment inhibited autophagy resulting in increase of ?-Syn oligomers, and compensatorily activated PERK signaling pathway...
  64. Lucke Wold B, Logsdon A, Turner R, Huber J, Rosen C. Endoplasmic Reticulum Stress Modulation as a Target for Ameliorating Effects of Blast Induced Traumatic Brain Injury. J Neurotrauma. 2017;34:S62-S70 pubmed publisher
    ..bTBI significantly increased markers of injury in the cortex of the left hemisphere: p-PERK and p-eIF2? at 30?min, p-T205 tau at 6?h, and iron at 24?h...
  65. Yiu A, Ibeh C, Roy S, Bandyopadhyay B. Melamine induces Ca2+-sensing receptor activation and elicits apoptosis in proximal tubular cells. Am J Physiol Cell Physiol. 2017;313:C27-C41 pubmed publisher
    ..Additionally, cells exposed to melamine displayed a rise in pERK activation and lactate dehydrogenase release resulting in cytotoxicity...
  66. Urra H, Dufey E, Avril T, Chevet E, Hetz C. Endoplasmic Reticulum Stress and the Hallmarks of Cancer. Trends Cancer. 2016;2:252-262 pubmed publisher
    ..The three main UPR signaling branches initiated by IRE1α, PERK, and ATF6 are crucial for tumor growth and aggressiveness as well as for microenvironment remodeling or resistance ..
  67. Ma Z, Yang Y, Di S, Feng X, Liu D, Jiang S, et al. Pterostilbene exerts anticancer activity on non-small-cell lung cancer via activating endoplasmic reticulum stress. Sci Rep. 2017;7:8091 pubmed publisher
    ..e., p-PERK, IRE1, ATF4, CHOP), thus decreasing the cell viability and inducing apoptosis in human PC9 and A549 NSCLC cell ..
  68. Yuan K, He H, Zhang C, Li X, Weng S, He J, et al. Litopenaeus vannamei activating transcription factor 6 alpha gene involvement in ER-stress response and white spot symptom virus infection. Fish Shellfish Immunol. 2017;70:129-139 pubmed publisher
    ..enzyme-1-X-box binding protein 1 (IRE1-XBP1) pathway and the protein kinase RNA (PKR)-like ER kinase-eIF2? (PERK-eIF2?) pathway of shrimp play roles in the unfolded protein response (UPR)...
  69. Altpere A, Raud S, Sütt S, Reimets R, Visnapuu T, Toots M, et al. Mild stress induces brain region-specific alterations of selective ER stress markers' mRNA expression in Wfs1-deficient mice. Behav Brain Res. 2018;352:94-98 pubmed publisher
    ..ER stress markers were studied: activating transcription factor 6? (Atf6?), protein kinase-like ER kinase (Perk), X-box binding protein 1 (Xbp1) and its spliced form (Xbp1s), 78-kilodalton glucose regulated protein (Grp78), 94-..
  70. Tang Y, Cai Q, Wang Y, Fan S, Zhang Z, Xiao M, et al. Protective effect of autophagy on endoplasmic reticulum stress induced apoptosis of alveolar epithelial cells in rat models of COPD. Biosci Rep. 2017;37: pubmed publisher
    ..The expressions of PKR-like ER kinase (PERK) and CCAAT/enhancer-binding protein-homologous protein (CHOP) were detected by immunohistochemistry...
  71. Chesnokova E, Bal N, Kolosov P. Kinases of eIF2a Switch Translation of mRNA Subset during Neuronal Plasticity. Int J Mol Sci. 2017;18: pubmed publisher
    ..the neuron-specific activity of four kinases: protein kinase R (PKR), PKR-like endoplasmic reticulum kinase (PERK), general control nonderepressible 2 kinase (GCN2), and heme-reguated eIF2? kinase (HRI), the substrate for which ..
  72. Suragani R, Kamindla R, Ehtesham N, Ramaiah K. Interaction of recombinant human eIF2 subunits with eIF2B and eIF2alpha kinases. Biochem Biophys Res Commun. 2005;338:1766-72 pubmed
    ..b>PERK, an eIF2alpha kinase, is found to interact with wt and mutants of eIF2alpha in which the serine 51 or 48 residue is ..
  73. Deegan S, Koryga I, Glynn S, Gupta S, Gorman A, Samali A. A close connection between the PERK and IRE arms of the UPR and the transcriptional regulation of autophagy. Biochem Biophys Res Commun. 2015;456:305-11 pubmed publisher
    ..the transcriptional upregulation of the autophagy receptor genes SQSTM1/p62, NBR1 and BNIP3L/NIX in response to ER stress and show that the inhibition of the UPR transmembrane receptors, PERK and IRE1, abrogates this upregulation.
  74. Go S, Kurita H, Yokoo K, Inden M, Kambe T, Hozumi I. Protective function of SLC30A10 induced via PERK-ATF4 pathway against 1-methyl-4-phenylpyridinium. Biochem Biophys Res Commun. 2017;490:1307-1313 pubmed publisher
    ..Considering that PKR-like endoplasmic reticulum kinase (PERK) pathway is activated under ER stress induced by MPP+, we investigated whether the expression of ..
  75. Majumdar A, Ahmad F, Sheikh T, Bhagat R, Pathak P, Joshi S, et al. miR-217-casein kinase-2 cross talk regulates ERK activation in ganglioglioma. J Mol Med (Berl). 2017;95:1215-1226 pubmed publisher
    ..miR-217 over-expression-mediated decrease in pERK, CK-2?, and mGluR1 levels was accompanied with increase in glycogen accumulation...
  76. Willson J, Muir C, Evered C, Cepeda M, Damjanovski S. Stable expression of ?1-antitrypsin Portland in MDA-MB-231 cells increased MT1-MMP and MMP-9 levels, but reduced tumour progression. J Cell Commun Signal. 2018;12:479-488 pubmed publisher
    ..At this low but optimal amount of MT1-MMP protein, changes to MT1-MMP levels are always mirrored by MMP-9 and pERK levels, and always opposite to MMP-2 levels...
  77. Zhao Z, Gao Y, Gao L, Zhang M, Wang H, Zhang C. Protective effects of bellidifolin in hypoxia-induced in pheochromocytoma cells (PC12) and underlying mechanisms. J Toxicol Environ Health A. 2017;80:1187-1192 pubmed publisher
    ..of immunohistochemical staining analysis revealed that there were no marked alterations in the expression of pERK protein between all bellidifolin groups while the expression of p-p38MAPK protein was significantly enhanced by ..
  78. Gerstenecker A, Roberson E, Schellenberg G, Standaert D, Shprecher D, Kluger B, et al. Genetic influences on cognition in progressive supranuclear palsy. Mov Disord. 2017;: pubmed publisher
  79. Liang G, Yang J, Wang Z, Li Q, Tang Y, Chen X. Polycystin-2 down-regulates cell proliferation via promoting PERK-dependent phosphorylation of eIF2alpha. Hum Mol Genet. 2008;17:3254-62 pubmed publisher
    ..phosphorylation of eukaryotic translation initiation factor eIF2alpha by pancreatic ER-resident eIF2alpha kinase (PERK)...
  80. van Vliet A, Agostinis P. PERK and filamin A in actin cytoskeleton remodeling at ER-plasma membrane contact sites. Mol Cell Oncol. 2017;4:e1340105 pubmed publisher
    The endoplasmic reticulum (ER) stress sensor protein kinase RNA-like endoplasmic reticulum kinase (PERK) plays a major role during the unfolded protein response (UPR), mainly through eIF2? phosphorylation...
  81. Park S, Jin Y, Park B. Dual control of the vestibulosympathetic reflex following hypotension in rats. Korean J Physiol Pharmacol. 2017;21:675-686 pubmed publisher
    ..Expression of pERK in the intermediolateral cell column (IMC) of the T4~7 thoracic spinal regions, blood epinephrine levels, and blood ..
  82. Avivar Valderas A, Salas E, Bobrovnikova Marjon E, Diehl J, Nagi C, Debnath J, et al. PERK integrates autophagy and oxidative stress responses to promote survival during extracellular matrix detachment. Mol Cell Biol. 2011;31:3616-29 pubmed publisher
    ..Here, we demonstrate that the endoplasmic reticulum kinase PERK facilitates survival of ECM-detached cells by concomitantly promoting autophagy, ATP production, and an antioxidant ..
  83. Brown M, Naidoo N. The endoplasmic reticulum stress response in aging and age-related diseases. Front Physiol. 2012;3:263 pubmed publisher
    ..This review will discuss age-related changes in the ER stress response and the role of the UPR in age-related diseases. ..
  84. Kim J, Heo S, Song I, Park I, Kim Y, Gong G, et al. Activation of the PERK-eIF2? Pathway Is Associated with Tumor-infiltrating Lymphocytes in HER2-Positive Breast Cancer. Anticancer Res. 2016;36:2705-11 pubmed
    ..TILs and the immunohistochemical expression of protein kinase RNA-like endoplasmic reticulum kinase (PERK), phospho-eukaryotic translation initiation factor 2? (p-eIF2?) and phosphorylated S6 (pS6) were evaluated in 447 ..
  85. Ji C, Yang B, Huang S, Huang J, Cheng B. Salubrinal protects human skin fibroblasts against UVB-induced cell death by blocking endoplasmic reticulum (ER) stress and regulating calcium homeostasis. Biochem Biophys Res Commun. 2017;493:1371-1376 pubmed publisher
    ..the depletion of ER Ca2+ and increased the expression of ER stress marker including phosphorylated PERK, CHOP, and phosphorylated IRE1?...
  86. Gugliotta G, Sudo M, Cao Q, Lin D, Sun H, Takao S, et al. Valosin-Containing Protein/p97 as a Novel Therapeutic Target in Acute Lymphoblastic Leukemia. Neoplasia. 2017;19:750-761 pubmed publisher
    ..and DNAJB9); 2) increased activation of IRE1-alpha, as demonstrated by the splicing of XBP1; and 3) activation of PERK, which resulted in a significant overexpression of CHOP, and its downstream genes...
  87. Zhang M, Liu X, Wang Q, Ru Y, Xiong X, Wu K, et al. NDRG2 acts as a PERK co-factor to facilitate PERK branch and ERS-induced cell death. FEBS Lett. 2017;591:3670-3681 pubmed publisher
    ..the three branches of unfolded protein response signaling, NDRG2 facilitates protein kinase RNA-like ER kinase (PERK) pathway via interaction with PERK, enhancing its downstream ATF4 and CHOP...
  88. VerPlank J, Lokireddy S, Feltri M, Goldberg A, Wrabetz L. Impairment of protein degradation and proteasome function in hereditary neuropathies. Glia. 2018;66:379-395 pubmed publisher
    ..the rate of protein degradation in S63del sciatic nerves and unexpectedly increased the phosphorylation of eIF2? by Perk. Thus, proteasome content, composition and activity are altered in these diseases and USP14 inhibitors have ..
  89. Arima Y. Studying Hardness Meter Spring Strength to Understand Hardness Distribution on Body Surfaces. J Acupunct Meridian Stud. 2017;10:340-345 pubmed publisher
    ..the spring strength of the contact portion main axis of a biological tissue hardness meter (product name: PEK)...
  90. Doolen S, Iannitti T, Shaw B, Grachen C, Donahue R, Taylor B. Fingolimod Reduces Neuropathic Pain Behaviors in a Mouse Model of Multiple Sclerosis by a Sphingosine-1 Phosphate Receptor 1-Dependent Inhibition of Central Sensitization in the Dorsal Horn. Pain. 2017;: pubmed publisher
    ..the spinal cord: glutamate-evoked Ca signaling and stimulus-evoked phospho-extracellular signal-related kinase ERK (pERK) expression, as well as upregulation of astrocytes (GFAP) and macrophage/microglia (Iba1) immunoreactivity...
  91. 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...
  92. Gao J, Zhang Y, Yu C, Tan F, Wang L. Spontaneous nonalcoholic fatty liver disease and ER stress in Sidt2 deficiency mice. Biochem Biophys Res Commun. 2016;476:326-332 pubmed publisher
    ..specific for unfolded protein response activation, Grp78 and CHOP, as well as significant elevation of downstream p-PERK, p-eIF2a, p-IRE1a, along with ER damage...