RONALD WEK

Summary

Affiliation: Indiana University
Country: USA

Publications

  1. pmc Parasite-specific eIF2 (eukaryotic initiation factor-2) kinase required for stress-induced translation control
    William 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
  2. ncbi request reprint Coping with stress: eIF2 kinases and translational control
    R C Wek
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Biochem Soc Trans 34:7-11. 2006
  3. pmc Phosphorylation of the alpha subunit of translation initiation factor-2 by PKR mediates protein synthesis inhibition in the mouse brain during status epilepticus
    Larissa 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
  4. pmc Selective control of amino acid metabolism by the GCN2 eIF2 kinase pathway in Saccharomyces cerevisiae
    John M Zaborske
    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA
    BMC Biochem 11:29. 2010
  5. doi request reprint Beta testing the antioxidant function of eIF2alpha phosphorylation in diabetes prevention
    Ronald C Wek
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Cell Metab 10:1-2. 2009
  6. ncbi request reprint 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
  7. 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
  8. pmc Stress-activated protein kinase pathway functions to support protein synthesis and translational adaptation in response to environmental stress in fission yeast
    Isabelle 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
  9. pmc Impaired growth and neurological abnormalities in branched-chain alpha-keto acid dehydrogenase kinase-deficient mice
    Mandar A Joshi
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Biochem J 400:153-62. 2006
  10. pmc A feedback transcriptional mechanism controls the level of the arginine/lysine transporter cat-1 during amino acid starvation
    Alex B Lopez
    Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH 44106 4906, USA
    Biochem J 402:163-73. 2007

Collaborators

Detail Information

Publications35

  1. pmc Parasite-specific eIF2 (eukaryotic initiation factor-2) kinase required for stress-induced translation control
    William 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
    ....
  2. ncbi request reprint Coping with stress: eIF2 kinases and translational control
    R C Wek
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Biochem Soc Trans 34:7-11. 2006
    ....
  3. pmc Phosphorylation of the alpha subunit of translation initiation factor-2 by PKR mediates protein synthesis inhibition in the mouse brain during status epilepticus
    Larissa 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
    ....
  4. pmc Selective control of amino acid metabolism by the GCN2 eIF2 kinase pathway in Saccharomyces cerevisiae
    John M Zaborske
    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA
    BMC Biochem 11:29. 2010
    ....
  5. doi request reprint Beta testing the antioxidant function of eIF2alpha phosphorylation in diabetes prevention
    Ronald C Wek
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Cell Metab 10:1-2. 2009
    ....
  6. ncbi request reprint 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
    ....
  7. 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
    ..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...
  8. pmc Stress-activated protein kinase pathway functions to support protein synthesis and translational adaptation in response to environmental stress in fission yeast
    Isabelle 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...
  9. pmc Impaired growth and neurological abnormalities in branched-chain alpha-keto acid dehydrogenase kinase-deficient mice
    Mandar 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...
  10. pmc A feedback transcriptional mechanism controls the level of the arginine/lysine transporter cat-1 during amino acid starvation
    Alex 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...
  11. ncbi request reprint The eukaryotic initiation factor-2 kinase pathway facilitates differential GADD45a expression in response to environmental stress
    Hao 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...
  12. pmc The GCN2 eIF2alpha kinase is required for adaptation to amino acid deprivation in mice
    Peichuan Zhang
    Department of Biology, The Pennsylvania State University, University Park 16802, USA
    Mol Cell Biol 22:6681-8. 2002
    ....
  13. pmc The unfolded protein response of B-lymphocytes: PERK-independent development of antibody-secreting cells
    Jennifer 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...
  14. ncbi request reprint The role of nitric oxide and the unfolded protein response in cytokine-induced beta-cell death
    Kari 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...
  15. doi request reprint Phosphorylation of eIF2 directs ATF5 translational control in response to diverse stress conditions
    Donghui 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...
  16. pmc Translational control of C-terminal Src kinase (Csk) expression by PRL3 phosphatase
    Fubo 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...
  17. pmc Translation regulation by eukaryotic initiation factor-2 kinases in the development of latent cysts in Toxoplasma gondii
    Jana 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...
  18. 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...
  19. ncbi request reprint IMPACT, a protein preferentially expressed in the mouse brain, binds GCN1 and inhibits GCN2 activation
    Catia 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...
  20. pmc Activating transcription factor 3 is integral to the eukaryotic initiation factor 2 kinase stress response
    Hao Yuan Jiang
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    Mol Cell Biol 24:1365-77. 2004
    ....
  21. ncbi request reprint Dimerization is required for activation of eIF2 kinase Gcn2 in response to diverse environmental stress conditions
    Jana 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...
  22. ncbi request reprint Preservation of liver protein synthesis during dietary leucine deprivation occurs at the expense of skeletal muscle mass in mice deleted for eIF2 kinase GCN2
    Tracy 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...
  23. pmc Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells
    Krishna 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...
  24. ncbi request reprint Regulation of internal ribosome entry site-mediated translation by eukaryotic initiation factor-2alpha phosphorylation and translation of a small upstream open reading frame
    James 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
    ....
  25. ncbi request reprint Uncharged tRNA and sensing of amino acid deficiency in mammalian piriform cortex
    Shuzhen 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...
  26. ncbi request reprint Phosphorylation of the alpha-subunit of the eukaryotic initiation factor-2 (eIF2alpha) reduces protein synthesis and enhances apoptosis in response to proteasome inhibition
    Hao 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...
  27. pmc Differential activation of eIF2 kinases in response to cellular stresses in Schizosaccharomyces pombe
    Ke 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...
  28. pmc GCN2 phosphorylation of eIF2alpha activates NF-kappaB in response to UV irradiation
    Hao 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...
  29. ncbi request reprint Role of glutamine depletion in directing tissue-specific nutrient stress responses to L-asparaginase
    Rachel 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...
  30. ncbi request reprint 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
    ....
  31. pmc Different effect of proteasome inhibition on vesicular stomatitis virus and poliovirus replication
    Nickolay 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...
  32. pmc Site-directed mutagenesis of the active site of diacylglycerol kinase alpha: calcium and phosphatidylserine stimulate enzyme activity via distinct mechanisms
    Takahiro 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...
  33. pmc Int6/eIF3e promotes general translation and Atf1 abundance to modulate Sty1 MAPK-dependent stress response in fission yeast
    Tsuyoshi 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...
  34. ncbi request reprint 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
    ....
  35. ncbi request reprint EXtENDINg beta cell survival by UPRegulating ATF4 translation
    Ronald 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 Grants21

  1. Metabolic stress responses and eIF2 kinase GCN2
    RONALD WEK; Fiscal Year: 2006
    ..abstract_text> ..
  2. Metabolic stress responses and eIF2 kinase GCN2
    RONALD WEK; Fiscal Year: 2007
    ....
  3. Translational Control by elF2 Kinase during ER Stress
    RONALD 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. ..
  4. Translational Control by elF-2 Kinase during ER Stress
    RONALD WEK; Fiscal Year: 2004
    ..Together, these studies will further our understanding of the mechanisms regulating general and gene-specific protein synthesis during ER stress. ..
  5. HISRS DOMAIN AND REGULATING GCN2 PROTEIN KINASE
    RONALD 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. ..
  6. Metabolic stress responses and eIF2 kinase GCN2
    Ronald C Wek; Fiscal Year: 2010
    ....