Research Topics
Species | RONALD WEKSummaryAffiliation: Indiana University Country: USA Publications
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Publications
Parasite-specific eIF2 (eukaryotic initiation factor-2) kinase required for stress-induced translation controlWilliam J Sullivan
Department of Pharmacology and Toxicology, Indiana University School of Medicine, 635 Barnhill Drive, Medical Sciences Bldg, Indianapolis, IN 46202, USA
Biochem J 380:523-31. 2004....
Coping with stress: eIF2 kinases and translational controlR C Wek
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Biochem Soc Trans 34:7-11. 2006....- Phosphorylation of the alpha subunit of translation initiation factor-2 by PKR mediates protein synthesis inhibition in the mouse brain during status epilepticusLarissa S Carnevalli
Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Sao Paulo, Rua Botucatu, 862, Sao Paulo, SP 04023 062, Brazil
Biochem J 397:187-94. 2006.... - Selective control of amino acid metabolism by the GCN2 eIF2 kinase pathway in Saccharomyces cerevisiaeJohn M Zaborske
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA
BMC Biochem 11:29. 2010.... 
Beta testing the antioxidant function of eIF2alpha phosphorylation in diabetes preventionRonald C Wek
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Cell Metab 10:1-2. 2009....- Translational control and the unfolded protein responseRonald C Wek
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
Antioxid Redox Signal 9:2357-71. 2007.... - Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 is required for activation of NF-kappaB in response to diverse cellular stressesHao Yuan Jiang
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
Mol Cell Biol 23:5651-63. 2003..The absence of NF-kappaB-mediated transcription and its antiapoptotic function provides an explanation for why eIF2alpha kinase deficiency in diseases such as Wolcott-Rallison syndrome leads to cellular apoptosis and disease... - Stress-activated protein kinase pathway functions to support protein synthesis and translational adaptation in response to environmental stress in fission yeastIsabelle Dunand-Sauthier
MRC Radiation and Genome Stability Unit, Harwell, Didcot, United Kingdom, and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, USA
Eukaryot Cell 4:1785-93. 2005..These findings suggest a role for the SAPK pathway in supporting translation initiation and facilitating adaptation to environmental stress in part through reducing eIF2alpha phosphorylation in fission yeast... - Impaired growth and neurological abnormalities in branched-chain alpha-keto acid dehydrogenase kinase-deficient miceMandar A Joshi
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Biochem J 400:153-62. 2006..The phenotype of the BDK-/- mice demonstrates the importance of tight regulation of oxidative disposal of BCAAs for normal growth and neurological function... - A feedback transcriptional mechanism controls the level of the arginine/lysine transporter cat-1 during amino acid starvationAlex B Lopez
Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH 44106 4906, USA
Biochem J 402:163-73. 2007..These results suggest that the transient increase in cat-1 transcription is due to transcriptional activation caused by ATF4 followed by transcriptional repression by ATF3 via a feedback mechanism... - The eukaryotic initiation factor-2 kinase pathway facilitates differential GADD45a expression in response to environmental stressHao Yuan Jiang
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
J Biol Chem 282:3755-65. 2007..This study highlights the molecular mechanisms by which environmental stresses can differentially control central regulatory proteins targeted by the eIF2 kinase pathway... - The GCN2 eIF2alpha kinase is required for adaptation to amino acid deprivation in micePeichuan Zhang
Department of Biology, The Pennsylvania State University, University Park 16802, USA
Mol Cell Biol 22:6681-8. 2002.... - The unfolded protein response of B-lymphocytes: PERK-independent development of antibody-secreting cellsJennifer N Gass
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University, Chicago, United States
Mol Immunol 45:1035-43. 2008..These data provide clear evidence for differential activation and utilization of distinct UPR components as activated B-lymphocytes increase Ig synthesis and differentiate into specialized secretory cells... - The role of nitric oxide and the unfolded protein response in cytokine-induced beta-cell deathKari T Chambers
Edward A Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, Missouri, USA
Diabetes 57:124-32. 2008..The UPR, activated by cytokine-induced nitric oxide (NO) production, has been proposed to mediate beta-cell death in response to cytokines. In this study, the role of UPR activation in cytokine-induced beta-cell death was examined... - Phosphorylation of eIF2 directs ATF5 translational control in response to diverse stress conditionsDonghui Zhou
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
J Biol Chem 283:7064-73. 2008..These results demonstrate that eIF2 kinases direct the translational expression of multiple transcription regulators by a mechanism involving delayed translation reinitiation... - Translational control of C-terminal Src kinase (Csk) expression by PRL3 phosphataseFubo Liang
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
J Biol Chem 283:10339-46. 2008..Thus, we have uncovered a previously uncharacterized role for PRL3 in the gene-specific translational control of Csk expression... - Translation regulation by eukaryotic initiation factor-2 kinases in the development of latent cysts in Toxoplasma gondiiJana Narasimhan
Department of Pharmacology and Toxicology and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
J Biol Chem 283:16591-601. 2008..Given its importance to pathogenesis, eIF2 kinase-mediated stress responses may provide opportunities for novel therapeutics... - Phosphorylation of eukaryotic initiation factor 2 by heme-regulated inhibitor kinase-related protein kinases in Schizosaccharomyces pombe is important for fesistance to environmental stressesKe 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... - IMPACT, a protein preferentially expressed in the mouse brain, binds GCN1 and inhibits GCN2 activationCatia M Pereira
Departamentos de Microbiologia, Imunologia, e Parasitologia and Fisiologia, Universidade Federal de Sao Paulo, São Paulo SP 04023 062, Brazil
J Biol Chem 280:28316-23. 2005..These results suggest that IMPACT ensures constant high levels of translation and low levels of ATF4 and CHOP in specific neuronal cells under amino acid starvation conditions... - Activating transcription factor 3 is integral to the eukaryotic initiation factor 2 kinase stress responseHao Yuan Jiang
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
Mol Cell Biol 24:1365-77. 2004.... - Dimerization is required for activation of eIF2 kinase Gcn2 in response to diverse environmental stress conditionsJana Narasimhan
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
J Biol Chem 279:22820-32. 2004..We conclude that dimerization involving hydrophobic segments in the carboxyl-terminal region is required for activation of Gcn2p in response to a multitude of stresses... - Preservation of liver protein synthesis during dietary leucine deprivation occurs at the expense of skeletal muscle mass in mice deleted for eIF2 kinase GCN2Tracy G Anthony
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Evansville, IN 47712, USA
J Biol Chem 279:36553-61. 2004..This study indicates that loss of GCN2 eIF2 kinase activity shifts the normal maintenance of protein mass away from skeletal muscle to provide substrate for continued hepatic translation... - Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cellsKrishna M Vattem
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Proc Natl Acad Sci U S A 101:11269-74. 2004..These results suggest that the mechanism of translation reinitiation involving uORFs is conserved from yeast to mammals... - Regulation of internal ribosome entry site-mediated translation by eukaryotic initiation factor-2alpha phosphorylation and translation of a small upstream open reading frameJames Fernandez
Departments of Nutrition and Biochemistry, The Veterans Affairs Medical Center, and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
J Biol Chem 277:2050-8. 2002.... - Uncharged tRNA and sensing of amino acid deficiency in mammalian piriform cortexShuzhen Hao
School of Veterinary Medicine, Department of Anatomy, Physiology and Cell Biology, University of California, Davis, CA 95616, USA
Science 307:1776-8. 2005..Thus, a basic mechanism of nutritional stress management functions in mammalian brain to guide food selection for survival... - Phosphorylation of the alpha-subunit of the eukaryotic initiation factor-2 (eIF2alpha) reduces protein synthesis and enhances apoptosis in response to proteasome inhibitionHao Yuan Jiang
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
J Biol Chem 280:14189-202. 2005..We conclude that eIF2alpha kinases are integral to cellular stress pathways induced by proteasome inhibitors, and may be central to the efficacy of anticancer drugs that target the ubiquitin/proteasome pathway... - Differential activation of eIF2 kinases in response to cellular stresses in Schizosaccharomyces pombeKe Zhan
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
Genetics 168:1867-75. 2004..Deletion of these eIF2 kinases renders S. pombe more sensitive to many of these stress conditions... - GCN2 phosphorylation of eIF2alpha activates NF-kappaB in response to UV irradiationHao-Yuan Jiang
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Biochem J 385:371-80. 2005..These results demonstrate that GCN2 is central to recognition of UV stress, and that eIF2alpha phosphorylation provides resistance to apoptosis in response to this environmental insult... - Role of glutamine depletion in directing tissue-specific nutrient stress responses to L-asparaginaseRachel B Reinert
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Evansville, Indiana 47712, USA
J Biol Chem 281:31222-33. 2006..Importantly, increased expression of asparagine synthetase and CHOP does not require eIF2 phosphorylation, signifying alternate or auxiliary means of inducing gene expression under conditions of amino acid depletion in the whole animal... - Wolcott-Rallison Syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneityValérie Senée
Génétique des Maladies Infectieuses et Autoimmunes, INSERM E102, Institut Pasteur, Paris, France
Diabetes 53:1876-83. 2004.... - Different effect of proteasome inhibition on vesicular stomatitis virus and poliovirus replicationNickolay Neznanov
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America
PLoS ONE 3:e1887. 2008..To our knowledge, this is the first study that connects the effect of stress induced by proteasome inhibition with the efficiency of viral infection... - Site-directed mutagenesis of the active site of diacylglycerol kinase alpha: calcium and phosphatidylserine stimulate enzyme activity via distinct mechanismsTakahiro Abe
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS 4053, Indianapolis, IN 46202, USA
Biochem J 375:673-80. 2003..Moreover, mutations of aspartate residues at the catalytic domain had differential effects on activation by Ca2+ and PS. These results indicate that Ca2+ and PS stimulate DAGKa via distinct mechanisms... - Int6/eIF3e promotes general translation and Atf1 abundance to modulate Sty1 MAPK-dependent stress response in fission yeastTsuyoshi Udagawa
Molecular Cellular and Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, Kansas 66506, USA
J Biol Chem 283:22063-75. 2008..Thus, the robust protein synthesis promoted by intact eIF3 appears to be a part of the requisites for sound Sty1 MAPK-dependent signaling governed by the activity of the Atf1 transcription factor... - Dimerization and release of molecular chaperone inhibition facilitate activation of eukaryotic initiation factor-2 kinase in response to endoplasmic reticulum stressKun Ma
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
J Biol Chem 277:18728-35. 2002.... - EXtENDINg beta cell survival by UPRegulating ATF4 translationRonald C Wek
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
Cell Metab 4:333-4. 2006..Regulation of this UPR pathway leads to enhanced translational expression of ATF4, a transcription factor central for stress remedy and cell survival...
Research Grants
- Metabolic stress responses and eIF2 kinase GCN2RONALD WEK; Fiscal Year: 2006..abstract_text> ..
- Metabolic stress responses and eIF2 kinase GCN2RONALD WEK; Fiscal Year: 2007....
- Translational Control by elF2 Kinase during ER StressRONALD WEK; Fiscal Year: 2007..Together, addressing these aims will increase our understanding of the process of cellular adaptation to environmental stresses and its impact in human disease. ..
- Translational Control by elF-2 Kinase during ER StressRONALD WEK; Fiscal Year: 2004..Together, these studies will further our understanding of the mechanisms regulating general and gene-specific protein synthesis during ER stress. ..
- HISRS DOMAIN AND REGULATING GCN2 PROTEIN KINASERONALD WEK; Fiscal Year: 2001..Additionally, these studies will determine the role of the new mammalian GCN2 kinase in the control of protein synthesis in nutrient-deprived mammalian cells. ..
- Metabolic stress responses and eIF2 kinase GCN2Ronald C Wek; Fiscal Year: 2010....