S R Kimball

Summary

Affiliation: Pennsylvania State University
Country: USA

Publications

  1. pmc Activation of the mammalian target of rapamycin complex 1 is both necessary and sufficient to stimulate eukaryotic initiation factor 2Bvarepsilon mRNA translation and protein synthesis
    Neil Kubica
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, United States
    Int J Biochem Cell Biol 40:2522-33. 2008
  2. pmc The mTORC1 signaling repressors REDD1/2 are rapidly induced and activation of p70S6K1 by leucine is defective in skeletal muscle of an immobilized rat hindlimb
    Andrew R Kelleher
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Am J Physiol Endocrinol Metab 304:E229-36. 2013
  3. pmc Induction of REDD1 gene expression in the liver in response to endoplasmic reticulum stress is mediated through a PERK, eIF2α phosphorylation, ATF4-dependent cascade
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Biochem Biophys Res Commun 427:485-9. 2012
  4. pmc Chronic insulin treatment of diabetes does not fully normalize alterations in the retinal transcriptome
    Georgina V Bixler
    Department of Pharmacology, Penn State College of Medicine, Hershey, PA, USA
    BMC Med Genomics 4:40. 2011
  5. ncbi request reprint Endotoxin induces differential regulation of mTOR-dependent signaling in skeletal muscle and liver of neonatal pigs
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Dr, Hershey, PA 17033, USA
    Am J Physiol Endocrinol Metab 285:E637-44. 2003
  6. ncbi request reprint Mammalian stress granules represent sites of accumulation of stalled translation initiation complexes
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol Cell Physiol 284:C273-84. 2003
  7. ncbi request reprint Developmental decline in components of signal transduction pathways regulating protein synthesis in pig muscle
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol Endocrinol Metab 282:E585-92. 2002
  8. pmc Control of translation initiation through integration of signals generated by hormones, nutrients, and exercise
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 285:29027-32. 2010
  9. ncbi request reprint Feeding stimulates protein synthesis in muscle and liver of neonatal pigs through an mTOR-dependent process
    S R Kimball
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol Endocrinol Metab 279:E1080-7. 2000
  10. ncbi request reprint Control of protein synthesis by amino acid availability
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, PO Box 850, Hershey, PA 17033, USA
    Curr Opin Clin Nutr Metab Care 5:63-7. 2002

Research Grants

  1. REGULATION OF PROTEIN TURNOVER IN SEPSIS
    Scot R Kimball; Fiscal Year: 2010

Collaborators

Detail Information

Publications124 found, 100 shown here

  1. pmc Activation of the mammalian target of rapamycin complex 1 is both necessary and sufficient to stimulate eukaryotic initiation factor 2Bvarepsilon mRNA translation and protein synthesis
    Neil Kubica
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, United States
    Int J Biochem Cell Biol 40:2522-33. 2008
    ....
  2. pmc The mTORC1 signaling repressors REDD1/2 are rapidly induced and activation of p70S6K1 by leucine is defective in skeletal muscle of an immobilized rat hindlimb
    Andrew R Kelleher
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Am J Physiol Endocrinol Metab 304:E229-36. 2013
    ..In conclusion, the results show an immobilization-induced attenuation of mTORC1 signaling mediated by induction of REDD1/2 and defective p70S6K1 phosphorylation...
  3. pmc Induction of REDD1 gene expression in the liver in response to endoplasmic reticulum stress is mediated through a PERK, eIF2α phosphorylation, ATF4-dependent cascade
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Biochem Biophys Res Commun 427:485-9. 2012
    ..Moreover, the induction of REDD1 gene expression was shown to require the protein kinase PERK and enhanced phosphorylation of its substrate, the α-subunit of eukaryotic initiation factor 2...
  4. pmc Chronic insulin treatment of diabetes does not fully normalize alterations in the retinal transcriptome
    Georgina V Bixler
    Department of Pharmacology, Penn State College of Medicine, Hershey, PA, USA
    BMC Med Genomics 4:40. 2011
    ..The goal of this study was to identify molecular changes in the rodent retina induced by diabetes that are not normalized by insulin replacement and restoration of euglycemia...
  5. ncbi request reprint Endotoxin induces differential regulation of mTOR-dependent signaling in skeletal muscle and liver of neonatal pigs
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Dr, Hershey, PA 17033, USA
    Am J Physiol Endocrinol Metab 285:E637-44. 2003
    ..This finding suggests that the initiator methionyl-tRNA-rather than the mRNA-binding step in translation initiation may play a more critical role in maintaining protein synthesis rates in the neonate during sepsis...
  6. ncbi request reprint Mammalian stress granules represent sites of accumulation of stalled translation initiation complexes
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol Cell Physiol 284:C273-84. 2003
    ..Finally, we also show that stress granules contain many, if not all, of the components of the 48S preinitiation complex, but not 60S ribosomal subunits, suggesting that they represent stalled translation initiation complexes...
  7. ncbi request reprint Developmental decline in components of signal transduction pathways regulating protein synthesis in pig muscle
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol Endocrinol Metab 282:E585-92. 2002
    ..7-day-old neonatal pigs is due in part to decreased content and/or activity of signaling components downstream of PI 3-kinase, e.g., PKB, mTOR, and S6K1...
  8. pmc Control of translation initiation through integration of signals generated by hormones, nutrients, and exercise
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 285:29027-32. 2010
    ..Together, modulation of these two regulatory steps in translation initiation accounts in large part for changes in protein synthesis in skeletal muscle produced by the integration of inputs from hormones, nutrients, and exercise...
  9. ncbi request reprint Feeding stimulates protein synthesis in muscle and liver of neonatal pigs through an mTOR-dependent process
    S R Kimball
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol Endocrinol Metab 279:E1080-7. 2000
    ..However, in skeletal muscle, these two processes may account for only part of the stimulation of protein synthesis, and thus additional steps may be involved in the response...
  10. ncbi request reprint Control of protein synthesis by amino acid availability
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, PO Box 850, Hershey, PA 17033, USA
    Curr Opin Clin Nutr Metab Care 5:63-7. 2002
    ..In this case, however, the signaling properties and mechanism of action of glutamine remain as an unsolved mystery...
  11. ncbi request reprint Regulation of protein synthesis by branched-chain amino acids
    S R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA
    Curr Opin Clin Nutr Metab Care 4:39-43. 2001
    ....
  12. ncbi request reprint Regulation of global and specific mRNA translation by amino acids
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    J Nutr 132:883-6. 2002
    ..Thus, deprivation of essential amino acids not only directly and rapidly represses global mRNA translation, but also potentially results in a reduction in the capacity to synthesize protein...
  13. ncbi request reprint Alterations in interprotein interactions between translation initiation factors assessed by fluorescence resonance energy transfer
    S R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, P O Box 850, Hershey, PA 17033, USA
    Int J Biochem Cell Biol 33:797-806. 2001
    ..Overall, the results demonstrate that fluorescence resonance energy transfer between EYFP--4E-BP1 and ECFP--eIF4E is a valuable tool in directly measuring alterations in the interaction of the two proteins...
  14. ncbi request reprint Eukaryotic initiation factor eIF2
    S R Kimball
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey 17033, USA
    Int J Biochem Cell Biol 31:25-9. 1999
    ..GTP.Met-tRNAi complex and inhibits global protein synthesis. Phosphorylation of eIF2 alpha occurs under a variety of conditions including viral infection, apoptosis, nutrient deprivation, heme-deprivation, and certain stresses...
  15. ncbi request reprint Leucine regulates translation of specific mRNAs in L6 myoblasts through mTOR-mediated changes in availability of eIF4E and phosphorylation of ribosomal protein S6
    S R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 274:11647-52. 1999
    ..Thus, leucine acting through an mTOR-dependent pathway stimulates the translation of specific mRNAs both by increasing the availability of eIF4E and by stimulating phosphorylation of S6...
  16. pmc Melatonin represses oxidative stress-induced activation of the MAP kinase and mTOR signaling pathways in H4IIE hepatoma cells through inhibition of Ras
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    J Pineal Res 44:379-86. 2008
    ..Overall, the results suggest that melatonin acts to prevent many of the H(2)O(2)-induced alterations in the MAPK and mTOR signaling pathways through inhibition of Ras, at least in H4IIE hepatoma cells...
  17. ncbi request reprint Role of amino acids in the translational control of protein synthesis in mammals
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Semin Cell Dev Biol 16:21-7. 2005
    ..The focus of this article is to review recent studies that have used intact animals as experimental models to examine the role of amino acids as modulators of signal transduction pathways...
  18. ncbi request reprint Interaction between the AMP-activated protein kinase and mTOR signaling pathways
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Med Sci Sports Exerc 38:1958-64. 2006
    ..The focus of the present review is to briefly summarize current knowledge concerning the regulation of mTOR signaling by AMPK...
  19. ncbi request reprint Glucagon represses signaling through the mammalian target of rapamycin in rat liver by activating AMP-activated protein kinase
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 279:54103-9. 2004
    ..Amino acids also enhance AMPK phosphorylation, although to a lesser extent than glucagon and amino acids combined...
  20. ncbi request reprint The role of nutrition in stimulating muscle protein accretion at the molecular level
    S R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, U S A
    Biochem Soc Trans 35:1298-301. 2007
    ..In addition, downstream effectors of TORC1 action on mRNA translation will be briefly presented. Finally, a previously unrecognized effector of TORC1 signalling in regulating protein synthesis will be described...
  21. ncbi request reprint A microtiter plate assay for assessing the interaction of eukaryotic initiation factor eIF4E with eIF4G and eIF4E binding protein-1
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Anal Biochem 325:364-8. 2004
    ..It also has the advantage that absolute amounts of the individual proteins can be easily estimated. The approach should be applicable to the study of a wide variety of protein-protein interactions...
  22. ncbi request reprint Implication of eIF2B rather than eIF4E in the regulation of global protein synthesis by amino acids in L6 myoblasts
    S R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 273:30945-53. 1998
    ..Furthermore, under the conditions employed herein, alterations in eIF4E availability are not rate-controlling for global protein synthesis but might be necessary for regulation of translation of specific mRNAs...
  23. pmc Rapid turnover of the mTOR complex 1 (mTORC1) repressor REDD1 and activation of mTORC1 signaling following inhibition of protein synthesis
    Scot R Kimball
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 283:3465-75. 2008
    ....
  24. ncbi request reprint Regulation of guanine nucleotide exchange through phosphorylation of eukaryotic initiation factor eIF2alpha. Role of the alpha- and delta-subunits of eiF2b
    S R Kimball
    Department of Cellular and Molecular Physiology, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 273:12841-5. 1998
    ..The results provide the first direct biochemical evidence that the alpha- and delta-subunits of eIF2B are involved in mediating the effect of substrate phosphorylation...
  25. pmc Simvastatin represses protein synthesis in the muscle-derived C₂C₁₂ cell line with a concomitant reduction in eukaryotic initiation factor 2B expression
    Alexander P Tuckow
    Dept of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA
    Am J Physiol Endocrinol Metab 300:E564-70. 2011
    ..These results suggest that repression of eIF2B expression and activity may contribute, at least in part, to the statin-induced reduction in protein synthesis...
  26. ncbi request reprint Deficiency of dietary EAA preferentially inhibits mRNA translation of ribosomal proteins in liver of meal-fed rats
    T G Anthony
    Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey, PA 17033, USA
    Am J Physiol Endocrinol Metab 281:E430-9. 2001
    ..Additionally, the translation of rp mRNAs is preferentially repressed in association with decreased S6K1 phosphorylation...
  27. ncbi request reprint Identification of interprotein interactions between the subunits of eukaryotic initiation factors eIF2 and eIF2B
    S R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 273:3039-44. 1998
    ....
  28. ncbi request reprint Chronic alcohol feeding impairs hepatic translation initiation by modulating eIF2 and eIF4E
    C H Lang
    Department of Cellular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol 277:E805-14. 1999
    ..In summary, these data suggest that chronic alcohol consumption impairs translation initiation in liver by altering eIF2B activity as well as eIF4F function via changes in eIF4E availability...
  29. ncbi request reprint Assessment of cell-signaling pathways in the regulation of mammalian target of rapamycin (mTOR) by amino acids in rat adipocytes
    P T Pham
    Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA
    J Cell Biochem 79:427-41. 2000
    ..Overall, our study emphasizes the need for caution when extending results obtained using established cell lines to the differentiated nondividing cells found in most tissues...
  30. ncbi request reprint Inhibition of muscle protein synthesis by alcohol is associated with modulation of eIF2B and eIF4E
    C H Lang
    Departments of Cellular and Molecular Physiology and Surgery, Pennsylvania State College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol 277:E268-76. 1999
    ..In summary, these data suggest that chronic alcohol consumption impairs translation initiation in muscle by altering multiple regulatory sites, including eIF2B activity and eIF4E availability...
  31. ncbi request reprint Amino acid-induced stimulation of translation initiation in rat skeletal muscle
    T C Vary
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol 277:E1077-86. 1999
    ..eIF4G complex controls protein synthesis in skeletal muscle when the amino acid concentration is above the physiological range, whereas removal of leucine reduces protein synthesis through changes in both eIF2B and eIF4E...
  32. ncbi request reprint Endotoxin-induced decrease in muscle protein synthesis is associated with changes in eIF2B, eIF4E, and IGF-I
    C H Lang
    Departments of Cellular and Molecular Physiology, and Surgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol Endocrinol Metab 278:E1133-43. 2000
    ....
  33. ncbi request reprint Identification of domains within the epsilon-subunit of the translation initiation factor eIF2B that are necessary for guanine nucleotide exchange activity and eIF2B holoprotein formation
    T G Anthony
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA
    Biochim Biophys Acta 1492:56-62. 2000
    ..In contrast, the C-terminal domain of eIF2B epsilon is sufficient alone for binding the beta-subunit of its substrate, eIF2, in vitro...
  34. ncbi request reprint Regulation of amino acid-sensitive TOR signaling by leucine analogues in adipocytes
    C J Lynch
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Cell Biochem 77:234-51. 2000
    ....
  35. ncbi request reprint Amino acid regulation of gene expression
    L S Jefferson
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    J Nutr 131:2460S-6S; discussion 2486S-7S. 2001
    ..It concludes with a consideration of some of the important unanswered questions in this rapidly advancing area of research...
  36. ncbi request reprint Oral administration of leucine stimulates ribosomal protein mRNA translation but not global rates of protein synthesis in the liver of rats
    T G Anthony
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    J Nutr 131:1171-6. 2001
    ..Furthermore, the translation of rp mRNA is disjointed from rates of total protein synthesis in liver and related to the degree of S6K1 phosphorylation...
  37. ncbi request reprint Subunit assembly and guanine nucleotide exchange activity of eukaryotic initiation factor-2B expressed in Sf9 cells
    J R Fabian
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 272:12359-65. 1997
    ..Furthermore, eIF-2Bepsilon is necessary and is perhaps sufficient for GEF activity in vitro...
  38. ncbi request reprint Initiation of protein synthesis in a cell-free system prepared from rat hepatocytes
    S R Kimball
    Department of Physiology, College of Medicine, Pennsylvania State University, Hershey 17033
    Am J Physiol 256:C28-34. 1989
    ..The cell-free system should provide a valuable tool for investigation of mechanisms involved in the regulation of initiation of protein synthesis...
  39. ncbi request reprint Regulation of protein synthesis after acute resistance exercise in diabetic rats
    P A Farrell
    Noll Physiological Research Center and Department of Kinesiology, University Park 16802 and Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol 276:E721-7. 1999
    ..This preserved response may be due to a compensatory increase in muscle IGF-I content and a maintained ability to activate eIF2B...
  40. ncbi request reprint Role of eIF4E in stimulation of protein synthesis by IGF-I in perfused rat skeletal muscle
    T C Vary
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol Endocrinol Metab 278:E58-64. 2000
    ..In contrast, the amount of eIF4E bound to eIF4G was increased threefold by IGF-I. We conclude that IGF-I regulates protein synthesis in skeletal muscle by enhancing formation of the active eIF4E x eIF4G complex...
  41. ncbi request reprint Insulin fails to stimulate muscle protein synthesis in sepsis despite unimpaired signaling to 4E-BP1 and S6K1
    T C Vary
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 10733, USA
    Am J Physiol Endocrinol Metab 281:E1045-53. 2001
    ..Thus the inability of insulin to stimulate protein synthesis during sepsis may be related to a defect in signaling to a step in translation initiation involved in assembly of an active eIF4F complex...
  42. ncbi request reprint Regulation of translation initiation by amino acids in eukaryotic cells
    S R Kimball
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Prog Mol Subcell Biol 26:155-84. 2001
    ..Thus, by preventing activation of GCN2, amino acids preserve eIF2B activity, which promotes translation of all mRNAs, i.e., global protein synthesis is enhanced...
  43. ncbi request reprint Mechanism of inhibition of peptide chain initiation by amino acid deprivation in perfused rat liver. Regulation involving inhibition of eukaryotic initiation factor 2 alpha phosphatase activity
    S R Kimball
    Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033
    J Biol Chem 266:1969-76. 1991
    ....
  44. ncbi request reprint Resistance exercise increases muscle protein synthesis and translation of eukaryotic initiation factor 2Bepsilon mRNA in a mammalian target of rapamycin-dependent manner
    Neil Kubica
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 280:7570-80. 2005
    ..These data suggest a novel link between mTOR signaling and eIF2Bepsilon mRNA translation that could contribute to the stimulation of protein synthesis following acute resistance exercise...
  45. ncbi request reprint Regulation of eukaryotic initiation factor-2B activity in muscle of diabetic rats
    A M Karinch
    Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033
    Am J Physiol 264:E101-8. 1993
    ..Modulation of casein kinase II activity may be a factor in the regulation of protein synthesis in muscle during acute diabetes. The activity of eIF-2B in heart might be maintained by the increased NADPH/NADP+...
  46. ncbi request reprint Glycogen synthase kinase-3 is the predominant insulin-regulated eukaryotic initiation factor 2B kinase in skeletal muscle
    L S Jefferson
    Department of Cellular and Molecular Physiology, Pennsylvania State University, College of Medicine, Hershey 17033, USA
    Int J Biochem Cell Biol 31:191-200. 1999
    ..Thus, insulin-mediated changes in eIF2B activity are likely to involve GSK-3...
  47. pmc Molecular cloning and characterization of cDNA encoding the alpha subunit of the rat protein synthesis initiation factor eIF-2B
    K M Flowers
    Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033, USA
    Proc Natl Acad Sci U S A 92:4274-8. 1995
    ..Southern blots indicate that the eIF-2B alpha cDNA also recognizes genomic DNA fragments from several other species, suggesting significant homology between the rat eIF-2B alpha gene and that from other species...
  48. ncbi request reprint AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling
    Douglas R Bolster
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 277:23977-80. 2002
    ..This is the first investigation to demonstrate changes in translation initiation and skeletal muscle protein synthesis in response to AMPK activation...
  49. ncbi request reprint Contribution of insulin to the translational control of protein synthesis in skeletal muscle by leucine
    Joshua C Anthony
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol Endocrinol Metab 282:E1092-101. 2002
    ..In contrast, assembly of the mRNA cap-binding complex occurs independently of increases in insulin and, by itself, is insufficient to stimulate rates of protein synthesis in skeletal muscle after leucine administration...
  50. ncbi request reprint Orally administered leucine enhances protein synthesis in skeletal muscle of diabetic rats in the absence of increases in 4E-BP1 or S6K1 phosphorylation
    Joshua C Anthony
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Diabetes 51:928-36. 2002
    ..The insulin-dependent mechanism is associated with increased phosphorylation of 4E-BP1 and S6K1. In contrast, the insulin-independent effect on protein synthesis is mediated by an unknown mechanism...
  51. ncbi request reprint Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine
    J C Anthony
    Department of Cellular and Molecular Physiology, P.O. Box 850, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    J Nutr 131:856S-860S. 2001
    ..The stimulatory effects of leucine on translation initiation are mediated in part through the protein kinase mammalian target of rapamycin (mTOR), where both insulin signaling and leucine signaling converge to promote a maximal response...
  52. ncbi request reprint Eukaryotic initiation factors and protein synthesis after resistance exercise in rats
    P A Farrell
    Noll Physiological Research Center and Graduate Program in Physiology, Pennsylvania State University, University Park 16802, USA
    J Appl Physiol 88:1036-42. 2000
    ..These new data, along with our previous report on eIF2B, suggest that the regulation of peptide chain initiation after exercise is more dependent on eIF2B than on the eIF4E system...
  53. ncbi request reprint Cloning and characterization of cDNA encoding rat hemin-sensitive initiation factor-2 alpha (eIF-2 alpha) kinase. Evidence for multitissue expression
    H Mellor
    Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033
    J Biol Chem 269:10201-4. 1994
    ..These findings raise the possibility of additional, uncharacterized roles for HCR in non-erythroid cells...
  54. pmc Immediate response of mammalian target of rapamycin (mTOR)-mediated signalling following acute resistance exercise in rat skeletal muscle
    Douglas R Bolster
    The Pennsylvania State University College of Medicine, Department of Cellular and Molecular Physiology, Hershey, PA 17033, USA
    J Physiol 553:213-20. 2003
    ....
  55. ncbi request reprint Effect of sepsis on eIE4E availability in skeletal muscle
    T C Vary
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
    Am J Physiol Endocrinol Metab 279:E1178-84. 2000
    ..Instead, on the basis of our previous studies, changes in eIF2B appear to be responsible for limiting protein synthesis in skeletal muscle during sepsis...
  56. ncbi request reprint Cloning and characterization of complementary and genomic DNAs encoding the epsilon-subunit of rat translation initiation factor-2B
    K M Flowers
    Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA
    Biochim Biophys Acta 1307:318-24. 1996
    ..Examination of the promoter region of the gene reveals a consensus binding site for the alpha-Pal transcription factor as well as possible cytokine-response elements and binding sites for testis-specific transcription factors...
  57. ncbi request reprint The mTOR signaling pathway mediates control of ribosomal protein mRNA translation in rat liver
    Ali K Reiter
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, P O Box 850, Hershey, PA 17033, USA
    Int J Biochem Cell Biol 36:2169-79. 2004
    ..The results suggest that in liver in vivo, mTOR-dependent signaling is critical for maximal stimulation of TOP mRNA translation...
  58. pmc Hydrogen peroxide impairs insulin-stimulated assembly of mTORC1
    Lianqin Zhang
    Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Free Radic Biol Med 46:1500-9. 2009
    ..These findings are consistent with PRAS40 functioning as a negative regulator of insulin-stimulated mTORC1 activity during oxidant stress...
  59. 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
    ....
  60. pmc The Src-family tyrosine kinase inhibitor PP1 interferes with the activation of ribosomal protein S6 kinases
    O Jameel Shah
    Department of Cellular and Molecular Physiology, College of Medicine, The Pennsylvania State University, 500 University Drive, Hershey, PA 17033, U S A
    Biochem J 366:57-62. 2002
    ..Thus activation of Src may supply a necessary signal for the activation of p70S6K1 and possibly other S6Ks...
  61. ncbi request reprint Assessment of biomarkers of protein anabolism in skeletal muscle during the life span of the rat: sarcopenia despite elevated protein synthesis
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey 17033, USA
    Am J Physiol Endocrinol Metab 287:E772-80. 2004
    ..The results are consistent with a model wherein protein synthesis is enhanced during aging in a futile attempt to maintain muscle mass...
  62. pmc AMPK represses TOP mRNA translation but not global protein synthesis in liver
    Ali K Reiter
    Department of Cellular and Molecular Physiology, The Pennsylvania State College of Medicine, PO Box 850, Hershey, PA 17033, USA
    Biochem Biophys Res Commun 374:345-50. 2008
    ..Thus, in liver, AMPK activation repressed translation of TOP mRNAs through a mechanism distinct from downregulated phosphorylation of S6K1 or rpS6...
  63. ncbi request reprint Beta -oxidation of free fatty acids is required to maintain translational control of protein synthesis in heart
    Stephen J Crozier
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol Endocrinol Metab 283:E1144-50. 2002
    ..Therefore, the activation state of signal transduction pathways that are responsive to cellular energy stress represents one mechanism whereby translation initiation may be regulated in cardiac muscle...
  64. ncbi request reprint Alcohol myopathy: impairment of protein synthesis and translation initiation
    C H Lang
    Department of Cellular and Molecular Physiology H166, Penn State College of Medicine, Hershey, PA 17033, USA
    Int J Biochem Cell Biol 33:457-73. 2001
    ..However, defects in the availability or effectiveness of various anabolic hormones, particularly insulin-like growth factor-I, are consistent with the alcohol-induced decrease in protein synthesis and translation initiation...
  65. ncbi request reprint Translational control of protein synthesis: implications for understanding changes in skeletal muscle mass
    L S Jefferson
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey 17033, USA
    Int J Sport Nutr Exerc Metab 11:S143-9. 2001
    ..Potential mechanisms for exercise-induced increase in muscle mass are discussed...
  66. ncbi request reprint Cloning and characterization of a cDNA encoding rat PKR, the double-stranded RNA-dependent eukaryotic initiation factor-2 kinase
    H Mellor
    Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033
    Biochim Biophys Acta 1219:693-6. 1994
    ..In addition, sequence elements in the 5'- and 3'-untranslated regions are also conserved between species...
  67. pmc Activation of signaling pathways and regulatory mechanisms of mRNA translation following myocardial ischemia-reperfusion
    Stephen J Crozier
    Dept of Cellular and Molecular Physiology, The Pennsylvania State Univ College of Medicine, PO Box 850, Hershey, PA 17033, USA
    J Appl Physiol 101:576-82. 2006
    ..These changes in protein phosphorylation suggest that control of mRNA translation following ischemia and reperfusion is modulated through a number of signaling pathways and regulatory mechanisms...
  68. ncbi request reprint Zinc stimulates the activity of the insulin- and nutrient-regulated protein kinase mTOR
    C J Lynch
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol Endocrinol Metab 281:E25-34. 2001
    ....
  69. ncbi request reprint Repression of protein synthesis and mTOR signaling in rat liver mediated by the AMPK activator aminoimidazole carboxamide ribonucleoside
    Ali K Reiter
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, P O Box 850, Hershey, PA 17033, USA
    Am J Physiol Endocrinol Metab 288:E980-8. 2005
    ..Overall, however, the results from both experimental models support a scenario in which AICAR directly represses protein synthesis and mTOR signaling in the liver through an AMPK-dependent mechanism...
  70. ncbi request reprint Leucine activates pancreatic translational machinery in rats and mice through mTOR independently of CCK and insulin
    Maria Dolors Sans
    Department of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, PA 17033, USA
    J Nutr 136:1792-9. 2006
    ..We conclude that leucine may participate, as a signal as well as a substrate, in activating the translational machinery in pancreatic acinar cells independently of hormonal effects and that this action is through the mTOR pathway...
  71. ncbi request reprint Regulation of protein synthesis associated with skeletal muscle hypertrophy by insulin-, amino acid- and exercise-induced signalling
    Douglas R Bolster
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, PO Box 850, Hershey, PA 17033, USA
    Proc Nutr Soc 63:351-6. 2004
    ....
  72. ncbi request reprint Cellular energy status modulates translational control mechanisms in ischemic-reperfused rat hearts
    Stephen J Crozier
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, PO Box 850, Hershey, PA 17033, USA
    Am J Physiol Heart Circ Physiol 289:H1242-50. 2005
    ....
  73. ncbi request reprint Tissue-specific regulation of protein synthesis by insulin and free fatty acids
    Stephen J Crozier
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Am J Physiol Endocrinol Metab 285:E754-62. 2003
    ..Thus FFAs may contribute to the translational control of protein synthesis in the heart but not in the gastrocnemius. In contrast, insulin, but not FFAs, is required for the maintenance of protein synthesis in the gastrocnemius...
  74. ncbi request reprint Dexamethasone represses signaling through the mammalian target of rapamycin in muscle cells by enhancing expression of REDD1
    Hongmei Wang
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 281:39128-34. 2006
    ..Overall, the data support the conclusion that REDD1 functions upstream of Tuberin and Rheb to down-regulate mTOR signaling in response to dexamethasone...
  75. pmc Glucagon acts in a dominant manner to repress insulin-induced mammalian target of rapamycin complex 1 signaling in perfused rat liver
    Jamie I Baum
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol Endocrinol Metab 297:E410-5. 2009
    ..Overall, the results suggest that glucagon acts in a dominant manner to repress insulin-induced mTORC1 signaling, which is in contrast to previous studies showing a dominant action of insulin in the control of hepatic gluconeogenesis...
  76. ncbi request reprint Regulation of global and specific mRNA translation by oral administration of branched-chain amino acids
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Biochem Biophys Res Commun 313:423-7. 2004
    ....
  77. ncbi request reprint Molecular mechanisms through which amino acids mediate signaling through the mammalian target of rapamycin
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Curr Opin Clin Nutr Metab Care 7:39-44. 2004
    ..The primary focus is on a protein kinase, termed the mammalian target of rapamycin (mTOR), that is a point of convergence between amino acid and growth factor signaling to mRNA translation and thereby to cell growth...
  78. 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
    ..These findings open an avenue for more focused future research toward groups of mRNAs that code for the early cellular stress response proteins...
  79. ncbi request reprint Oral leucine administration stimulates protein synthesis in rat skeletal muscle
    Stephen J Crozier
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    J Nutr 135:376-82. 2005
    ..The ability of small doses of leucine to stimulate skeletal muscle protein synthesis suggests that future research on the regulation of skeletal muscle protein synthesis by orally administered leucine will be feasible in humans...
  80. ncbi request reprint Inhibition of mammalian translation initiation by volatile anesthetics
    Laura K Palmer
    Dept of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Dr, Hershey, PA 17033, USA
    Am J Physiol Endocrinol Metab 290:E1267-75. 2006
    ..Thus dose- and time-dependent alterations in multiple processes permit liver cells to adapt translation to variable degrees and duration of stress imposed by anesthetic exposure...
  81. ncbi request reprint Leucine regulates translation initiation in rat skeletal muscle via enhanced eIF4G phosphorylation
    Douglas R Bolster
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    J Nutr 134:1704-10. 2004
    ..eIF4G assembly and protein synthesis directly in skeletal muscle, possibly by augmenting phosphorylation of eIF4G through a signaling pathway independent of mTOR...
  82. ncbi request reprint Invited Review: Role of insulin in translational control of protein synthesis in skeletal muscle by amino acids or exercise
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Appl Physiol 93:1168-80. 2002
    ..This review summarizes the results of a number of recent studies that have helped to establish our present understanding of the interactions of insulin, amino acids, and exercise in the regulation of protein synthesis in skeletal muscle...
  83. ncbi request reprint Glucosamine-induced phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 is mediated by the protein kinase R-like endoplasmic-reticulum associated kinase
    Christina Leah B Kline
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, 17033, USA
    Int J Biochem Cell Biol 38:1004-14. 2006
    ....
  84. ncbi request reprint New functions for amino acids: effects on gene transcription and translation
    Scot R Kimball
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033 0850, USA
    Am J Clin Nutr 83:500S-507S. 2006
    ....
  85. ncbi request reprint Hypertrophy of skeletal muscle in diabetic rats in response to chronic resistance exercise
    P A Farrell
    Noll Physiological Research Center and Department of Kinesiology, University Park, Pennsylvania 16802, USA
    J Appl Physiol 87:1075-82. 1999
    ..These data demonstrate that, despite lower circulating insulin concentrations, diabetic rats can increase muscle mass in response to a physiological stimulus...
  86. pmc Ablation of 4E-BP1/2 prevents hyperglycemia-mediated induction of VEGF expression in the rodent retina and in Muller cells in culture
    Tabitha L Schrufer
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
    Diabetes 59:2107-16. 2010
    ..Here, we tested the hypothesis that hyperglycemia mediates induction of VEGF expression in a eukaryotic initiation factor 4E (eIF4E) binding protein (4E-BP) 1 and 2 dependent manner...
  87. ncbi request reprint Time course changes in signaling pathways and protein synthesis in C2C12 myotubes following AMPK activation by AICAR
    David L Williamson
    Dept of Cellular and Molecular Physiology, H166, Pennsylvania State University College of Medicine, 500 University Dr, Hershey, PA 17033, USA
    Am J Physiol Endocrinol Metab 291:E80-9. 2006
    ....
  88. ncbi request reprint Sex-dependent differences in the regulation of myocardial protein synthesis following long-term ethanol consumption
    Thomas C Vary
    Department of Cellular and Molecular Physiology, Penn State University College of Medicine, H166, 500 University Dr, Hershey, PA 17033, USA
    Am J Physiol Regul Integr Comp Physiol 292:R778-87. 2007
    ..The failure of female rats consuming ethanol to show structural changes appears related to the inability of ethanol to affect the regulation protein synthesis to the same extent as their male counterparts...
  89. pmc Exercise-induced alterations in extracellular signal-regulated kinase 1/2 and mammalian target of rapamycin (mTOR) signalling to regulatory mechanisms of mRNA translation in mouse muscle
    David L Williamson
    Department of Cellular and Molecular Physiology, H166 The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA
    J Physiol 573:497-510. 2006
    ....
  90. ncbi request reprint Rapamycin blunts nutrient stimulation of eIF4G, but not PKCepsilon phosphorylation, in skeletal muscle
    Thomas C Vary
    Department of Cellular and Molecular Physiology, Rm C4710, Penn State University College of Medicine, H166, 500 University Drive, Hershey, PA 17033, USA
    Am J Physiol Endocrinol Metab 293:E188-96. 2007
    ..The latter observation implies that the effects observed with rapamycin were the result of modulation of skeletal muscle signaling mechanisms responsible for eIF4G phosphorylation...
  91. pmc Elevated corticosterone associated with food deprivation upregulates expression in rat skeletal muscle of the mTORC1 repressor, REDD1
    Nora K McGhee
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    J Nutr 139:828-34. 2009
    ..Overall, the results demonstrate that changes in REDD1 expression likely contribute to the regulation of mTORC1 signaling during food deprivation and refeeding...
  92. ncbi request reprint Effects of alpha-difluoromethylornithine on thrombospondin-1 production by human breast cancer cells
    Andrea Manni
    Division of Endocrinology, Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Int J Oncol 31:1187-91. 2007
    ..The reason for this unexpected finding is unknown but may be due to DFMO-induced stimulation of TSP-1 secretion into the systemic circulation, thus preventing its accumulation within the tumor...
  93. ncbi request reprint Signaling pathways and molecular mechanisms through which branched-chain amino acids mediate translational control of protein synthesis
    Scot R Kimball
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA, USA
    J Nutr 136:227S-31S. 2006
    ..The current state of our understanding of how leucine acts on these signaling pathways and molecular mechanisms to stimulate protein synthesis in skeletal muscle is summarized in this article...
  94. ncbi request reprint Amino acids as regulators of gene expression at the level of mRNA translation
    Leonard S Jefferson
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    J Nutr 133:2046S-2051S. 2003
    ..Finally, it provides examples of mRNAs whose translation is modulated through these mechanisms...
  95. ncbi request reprint Alterations in mitogen-activated protein kinase kinase and extracellular regulated kinase signaling in theca cells contribute to excessive androgen production in polycystic ovary syndrome
    Velen L Nelson-Degrave
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine 500 University Drive H166, Hershey, Pennsylvania 17033, USA
    Mol Endocrinol 19:379-90. 2005
    ..These findings implicate alterations in the MAPK pathway in the pathogenesis of excessive ovarian androgen production in PCOS...
  96. ncbi request reprint Phosphorylation of eukaryotic initiation factor eIF2Bepsilon in skeletal muscle during sepsis
    Thomas C Vary
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol Endocrinol Metab 283:E1032-9. 2002
    ..Furthermore, the study presents the first demonstration of changes in eIF2Bepsilon phosphorylation in vivo...
  97. ncbi request reprint Alcohol impairs leucine-mediated phosphorylation of 4E-BP1, S6K1, eIF4G, and mTOR in skeletal muscle
    Charles H Lang
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Am J Physiol Endocrinol Metab 285:E1205-15. 2003
    ..Hence, ethanol produces a leucine resistance in skeletal muscle, as evidenced by the impaired phosphorylation of 4E-BP1, eIF4G, S6K1, and mTOR, that is independent of elevations in endogenous glucocorticoids...
  98. ncbi request reprint The activated glucocorticoid receptor modulates presumptive autoregulation of ribosomal protein S6 protein kinase, p70 S6K
    O Jameel Shah
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033 0850, USA
    J Biol Chem 277:2525-33. 2002
    ....
  99. ncbi request reprint Structure and sequence of the gene encoding the alpha-subunit of rat translation initiation factor-2B
    K M Flowers
    Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033, USA
    Biochim Biophys Acta 1264:163-7. 1995
    ....
  100. doi request reprint A multistep validation process of biomarkers for preclinical drug development
    W M Freeman
    Functional Genomics Core Facility, Penn State College of Medicine, Hershey, PA 17033, USA
    Pharmacogenomics J 10:385-95. 2010
    ....
  101. ncbi request reprint Severe diabetes inhibits resistance exercise-induced increase in eukaryotic initiation factor 2B activity
    J C Kostyak
    Noll Physiological Research Center and Department of Kinesiology, Pennsylvania State University, University Park 16802, USA
    J Appl Physiol 91:79-84. 2001
    ..05) than in nondiabetic animals. These data suggest that severe hypoinsulinemia is associated with an inability to increase eIF2B activity in response to exercise...

Research Grants1

  1. REGULATION OF PROTEIN TURNOVER IN SEPSIS
    Scot R Kimball; Fiscal Year: 2010
    ....