PEK

Summary

Gene Symbol: PEK
Description: pancreatic eIF-2alpha kinase
Alias: CG2087, DPERK, DmPEK, Dmel\CG2087, DpERK, PERK, Pek, Perk, dPERK, dPerk, pERK, pek, perk, pancreatic eIF-2alpha kinase, CG2087-PA, CG2087-PB, CG2087-PC, PEK-PA, PEK-PB, PEK-PC, PERK, pancreatic eIF2alpha kinase
Species: fruit fly
Products:     PEK

Top Publications

  1. Kim H, Raphael A, LADOW E, McGurk L, Weber R, Trojanowski J, et al. Therapeutic modulation of eIF2? phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models. Nat Genet. 2014;46:152-60 pubmed publisher
    ..These findings indicate that the dysfunction induced by prolonged stress granule formation might contribute directly to ALS and that compounds that mitigate this process may represent a novel therapeutic approach. ..
  2. Malzer E, Daly M, Moloney A, Sendall T, Thomas S, Ryder E, et al. Impaired tissue growth is mediated by checkpoint kinase 1 (CHK1) in the integrated stress response. J Cell Sci. 2010;123:2892-900 pubmed publisher
    ..Overexpression of the ISR kinase PERK resulted in a striking atrophic eye phenotype in Drosophila melanogaster that could be rescued by co-expressing the ..
  3. Kang M, Chung J, Ryoo H. CDK5 and MEKK1 mediate pro-apoptotic signalling following endoplasmic reticulum stress in an autosomal dominant retinitis pigmentosa model. Nat Cell Biol. 2012;14:409-15 pubmed publisher
    ..These findings establish a previously unrecognized branch of ER-stress response signalling involved in degenerative diseases. ..
  4. Sood R, Porter A, Ma K, Quilliam L, Wek R. Pancreatic eukaryotic initiation factor-2alpha kinase (PEK) homologues in humans, Drosophila melanogaster and Caenorhabditis elegans that mediate translational control in response to endoplasmic reticulum stress. Biochem J. 2000;346 Pt 2:281-93 pubmed
    ..PEK, also referred to as RNA-dependent protein kinase (PKR)-like endoplasmic reticulum (ER) kinase (PERK) is a transmembrane protein implicated in translational control in response to stresses that impair protein folding ..
  5. Pomar N, Berlanga J, Campuzano S, Hernández G, Elías M, de Haro C. Functional characterization of Drosophila melanogaster PERK eukaryotic initiation factor 2alpha (eIF2alpha) kinase. Eur J Biochem. 2003;270:293-306 pubmed
    ..In this study, we have characterized the second eIF2alpha kinase found in Drosophila, a PERK homologue (DPERK). Expression of DPERK is developmentally regulated...
  6. Ryoo H. Drosophila as a model for unfolded protein response research. BMB Rep. 2015;48:445-53 pubmed
    ..The fact that the basic UPR pathways are conserved, together with the availability of many human disease models in this organism, makes Drosophila a powerful tool for studying human disease mechanisms. ..
  7. Malzer E, Szajewska Skuta M, Dalton L, Thomas S, Hu N, Skaer H, et al. Coordinate regulation of eIF2α phosphorylation by PPP1R15 and GCN2 is required during Drosophila development. J Cell Sci. 2013;126:1406-15 pubmed publisher
    ..Moreover, we show that its expression is necessary for embryonic and larval development and that this is to oppose the inhibitory effects of GCN2 on anabolic growth. ..
  8. Demay Y, Perochon J, Szuplewski S, Mignotte B, Gaumer S. The PERK pathway independently triggers apoptosis and a Rac1/Slpr/JNK/Dilp8 signaling favoring tissue homeostasis in a chronic ER stress Drosophila model. Cell Death Dis. 2014;5:e1452 pubmed publisher
    ..We observed, in this novel model of chronic ER-stress, a PERK/ATF4-dependent apoptosis requiring downregulation of the antiapoptotic diap1 gene...
  9. Thomas S, Malzer E, Ordóñez A, Dalton L, van t Wout E, Liniker E, et al. p53 and translation attenuation regulate distinct cell cycle checkpoints during endoplasmic reticulum (ER) stress. J Biol Chem. 2013;288:7606-17 pubmed publisher
    ..We propose that cell cycle regulation in response to ER stress comprises redundant pathways invoked sequentially first to impair G(2) progression prior to ultimate G(1) arrest. ..

More Information

Publications25

  1. Kirilly D, Wang S, Xie T. Self-maintained escort cells form a germline stem cell differentiation niche. Development. 2011;138:5087-97 pubmed publisher
    ..Here, we propose that ECs form a niche that controls GSC lineage differentiation and is maintained by a non-stem cell mechanism. ..
  2. Farny N, Kedersha N, Silver P. Metazoan stress granule assembly is mediated by P-eIF2alpha-dependent and -independent mechanisms. RNA. 2009;15:1814-21 pubmed publisher
    ..We further examine the role of the two Drosophila eIF2alpha kinases, PEK and GCN2, in regulating SG formation in response to heat and arsenite stress...
  3. Liu Y, Lu W, BRUMMEL T, Yuh C, Lin P, Kao T, et al. Reduced expression of alpha-1,2-mannosidase I extends lifespan in Drosophila melanogaster and Caenorhabditis elegans. Aging Cell. 2009;8:370-9 pubmed publisher
    ..These findings suggested that mutations in mas1 may extend longevity by modulating DR. ..
  4. Nagy P, Varga A, Pircs K, Hegedűs K, Juhász G. Myc-driven overgrowth requires unfolded protein response-mediated induction of autophagy and antioxidant responses in Drosophila melanogaster. PLoS Genet. 2013;9:e1003664 pubmed publisher
    ..Mechanistically, Myc overexpression increases unfolded protein response (UPR), which leads to PERK-dependent autophagy induction and may be responsible for p62 accumulation...
  5. Moore K, Plant J, Gaddam D, Craft J, Hollien J. Regulation of sumo mRNA during endoplasmic reticulum stress. PLoS ONE. 2013;8:e75723 pubmed publisher
    ..Unlike other RIDD targets, the sumo transcript does not stably associate with the ER membrane, but instead relies on an Xbp1-like stem loop and a second UPR mediator, Perk, for its degradation during stress.
  6. Wang L, Ryoo H, Qi Y, Jasper H. PERK Limits Drosophila Lifespan by Promoting Intestinal Stem Cell Proliferation in Response to ER Stress. PLoS Genet. 2015;11:e1005220 pubmed publisher
    ..Here we show that the PKR-like ER kinase (PERK) integrates both cell-autonomous and non-autonomous ER stress stimuli to induce ISC proliferation...
  7. Lindström R, Lindholm P, Kallijärvi J, Palgi M, Saarma M, Heino T. Exploring the Conserved Role of MANF in the Unfolded Protein Response in Drosophila melanogaster. PLoS ONE. 2016;11:e0151550 pubmed publisher
    ..vivo approach we found genetic interactions between Drosophila Manf and genes encoding for Drosophila homologues of GRP78, PERK and XBP1, the key components of UPR. Our data suggest a role for Manf in the regulation of Drosophila UPR.
  8. Zhang Y, Cui C, Lai Z. The defender against apoptotic cell death 1 gene is required for tissue growth and efficient N-glycosylation in Drosophila melanogaster. Dev Biol. 2016;420:186-195 pubmed publisher
    ..Furthermore, Perk-Atf4 signaling, one branch of UPR pathways, appears to play a dual role in inducing cell apoptosis and mediating ..
  9. Kim K, Kim S, Kim J, Kim H, Yim J. Glutathione s-transferase omega 1 activity is sufficient to suppress neurodegeneration in a Drosophila model of Parkinson disease. J Biol Chem. 2012;287:6628-41 pubmed publisher
    ..Our results suggest a novel mechanism for the protective role of DmGSTO1 in parkin mutants, through the regulation of ATP synthase activity, and provide insight into potential therapies for Parkinson disease neurodegeneration. ..
  10. Park S, Ludwig M, Tamarina N, He B, Carl S, Dickerson D, et al. Genetic complexity in a Drosophila model of diabetes-associated misfolded human proinsulin. Genetics. 2014;196:539-55 pubmed publisher
    ..The genetic dominance of disease-specific phenotypic variability in our model of misfolded human proinsulin makes this approach amenable to genome-wide association study in a simple F1 screen of natural variation. ..
  11. Katz M, Acevedo J, Loenarz C, Galagovsky D, Liu Yi P, Pérez Pepe M, et al. Sudestada1, a Drosophila ribosomal prolyl-hydroxylase required for mRNA translation, cell homeostasis, and organ growth. Proc Natl Acad Sci U S A. 2014;111:4025-30 pubmed publisher
    ..These observations, together with those on enzyme homologs described in the companion articles, reveal conserved biochemical and biological roles for a widely distributed ribosomal oxygenase. ..
  12. Mounir Z, Krishnamoorthy J, Wang S, Papadopoulou B, Campbell S, Muller W, et al. Akt determines cell fate through inhibition of the PERK-eIF2? phosphorylation pathway. Sci Signal. 2011;4:ra62 pubmed publisher
    ..also occurred in Drosophila cells and depended on the endoplasmic reticulum (ER)-resident protein kinase PERK, which was inhibited by Akt-dependent phosphorylation at threonine-799...
  13. Ryoo H, Steller H. Unfolded protein response in Drosophila: why another model can make it fly. Cell Cycle. 2007;6:830-5 pubmed
    ..Here, we review the molecular components of the Drosophila UPR as well as the disease models that may be affected by this signaling pathway. ..
  14. Gonzalez J, Qi H, Liu N, Lin H. Piwi Is a Key Regulator of Both Somatic and Germline Stem Cells in the Drosophila Testis. Cell Rep. 2015;12:150-161 pubmed publisher
    ..Our work reveals the cell-autonomous function of Piwi in both somatic and germline stem cell types, with somatic function possibly via its epigenetic mechanism. ..
  15. Celardo I, Costa A, Lehmann S, Jones C, Wood N, Mencacci N, et al. Mitofusin-mediated ER stress triggers neurodegeneration in pink1/parkin models of Parkinson's disease. Cell Death Dis. 2016;7:e2271 pubmed publisher
    ..Further, both genetic inhibition of dPerk-dependent ER stress signalling and pharmacological inhibition using the PERK inhibitor GSK2606414 were ..
  16. Ninov N, Manjón C, Martin Blanco E. Dynamic control of cell cycle and growth coupling by ecdysone, EGFR, and PI3K signaling in Drosophila histoblasts. PLoS Biol. 2009;7:e1000079 pubmed publisher
    ..It sets the stage for the comprehensive understanding of the coordination of cell growth and cell-cycle progression in complex multicellular eukaryotes. ..