Eif4ebp1

Summary

Gene Symbol: Eif4ebp1
Description: eukaryotic translation initiation factor 4E binding protein 1
Alias: PHAS-I, eukaryotic translation initiation factor 4E-binding protein 1, 4E-BP1, eIF4E-binding protein 1, phosphorylated heat- and acid-stable protein regulated by insulin 1
Species: rat

Top Publications

  1. ncbi Activated eIF4E-binding protein slows G1 progression and blocks transformation by c-myc without inhibiting cell growth
    Mary Lynch
    Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA
    J Biol Chem 279:3327-39. 2004
  2. ncbi PHAS-I as a link between mitogen-activated protein kinase and translation initiation
    T A Lin
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110
    Science 266:653-6. 1994
  3. doi Molecular mechanisms of mTOR-mediated translational control
    Xiaoju Max Ma
    Department of Research Oncology Diagnostics, Genentech Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nat Rev Mol Cell Biol 10:307-18. 2009
  4. pmc Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism
    A C Gingras
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, H3G 1Y6, Canada
    Genes Dev 13:1422-37. 1999
  5. ncbi Dissociation of the eukaryotic initiation factor-4E/4E-BP1 complex involves phosphorylation of 4E-BP1 by an mTOR-associated kinase
    K J Heesom
    Department of Biochemistry, School of Medical Sciences, University Walk, Bristol, UK
    FEBS Lett 457:489-93. 1999
  6. pmc Distinct signaling events downstream of mTOR cooperate to mediate the effects of amino acids and insulin on initiation factor 4E-binding proteins
    Xuemin Wang
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dow St, Dundee DD1 5EH, United Kingdom
    Mol Cell Biol 25:2558-72. 2005
  7. doi 4-Nonylphenol induces autophagy and attenuates mTOR-p70S6K/4EBP1 signaling by modulating AMPK activation in Sertoli cells
    Peng Duan
    MOE Ministry of Education key lab of Environment and Health, Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China Research Center for Environment and Health, Hubei University of Medicine, Shiyan 442000, China
    Toxicol Lett . 2016
  8. doi mTOR/P70S6K promotes spermatogonia proliferation and spermatogenesis in Sprague Dawley rats
    Hao Xu
    Department of Paediatric Research Institute, Children s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
    Reprod Biomed Online 32:207-17. 2016
  9. pmc Rotenone induction of hydrogen peroxide inhibits mTOR-mediated S6K1 and 4E-BP1/eIF4E pathways, leading to neuronal apoptosis
    Qian Zhou
    Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Jiangsu Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University, Nanjing 210023, P R China, Department of Biochemistry and Molecular Biology and Feist Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130 3932
    Toxicol Sci 143:81-96. 2015
  10. doi Everolimus sensitizes Ras-transformed cells to radiation in vitro through the autophagy pathway
    Yu Chieh Su
    Department of Hematological Oncology, Buddhist Dalin Tzu Chi Hospital, Chiayi 62247, Taiwan, R O C
    Int J Mol Med 34:1417-22. 2014

Scientific Experts

  • S R Kimball
  • Charles Lang
  • Gail Otulakowski
  • E Mezey
  • Valerie Petegnief
  • K J Heesom
  • Li Sui
  • Stephen Marshall
  • THOMAS VARY
  • Hao Xu
  • Peng Duan
  • Qian Zhou
  • Yu Chieh Su
  • Kimberly Coffman
  • Lance F Dasilva
  • Masaru Takabatake
  • Ji Tain Xu
  • María I Ayuso
  • Miho Ohsumi
  • Xiaoju Max Ma
  • David M Thomson
  • Guo Dong Sun
  • Jessica D Bishop
  • Katsuhiko Funai
  • A O'Loghlen
  • E P Connolly
  • J C Lawrence
  • Xuemin Wang
  • A H Stephenson
  • Mary Lynch
  • Hidetoshi Ban
  • Christopher G Proud
  • Wei Chen
  • Francis L Martin
  • Tingting Yu
  • Junlin He
  • Yubin Ding
  • Yingxiong Wang
  • Lianju Shen
  • Xueqing Liu
  • Xuemei Chen
  • Chunhui Hu
  • Jing Zhu
  • Wenting Huang
  • Sha Tang
  • Chao Quan
  • Yuqin Shi
  • Kedi Yang
  • Jinfei Zhang
  • Shile Huang
  • Wen Liu
  • Hai Zhang
  • Long Chen
  • Ruijie Zhang
  • Lei Liu
  • Chunxiao Liu
  • Jia Liu
  • Chong Xu
  • Shan Lu
  • Shih Kai Hung
  • Bing Yang
  • Chun Tang
  • Meng Qiu Dong
  • Ling Chien Hung
  • Wen Yen Chiou
  • Da Chuan Guo
  • Shu Ling Fu
  • Emelia Pelliccio
  • Jie Lu
  • Andrew R Tee
  • Chih Chia Yu
  • Hon Yi Lin
  • Jeng Jong Hwang
  • Heidi L Kenerson
  • Fuyuhiko Tamanoi
  • Fei Ting Hsu
  • Moon Sing Lee
  • Ashley L Tetlow
  • Megan J Davey
  • Julie Genereaux
  • Christopher J Brandl
  • Gregory B Gloor
  • Samantha Pillon
  • Jim Karagiannis
  • T G Anthony
  • M W Potter
  • T A Lin
  • Tatsuhiko Imaoka
  • Yoshiya Shimada
  • Masahiro Fukushi

Detail Information

Publications45

  1. ncbi Activated eIF4E-binding protein slows G1 progression and blocks transformation by c-myc without inhibiting cell growth
    Mary Lynch
    Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA
    J Biol Chem 279:3327-39. 2004
    ..It further identifies G(1) control by translation initiation factors as an essential genetic target of c-myc that is necessary for its ability to transform cells...
  2. ncbi PHAS-I as a link between mitogen-activated protein kinase and translation initiation
    T A Lin
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110
    Science 266:653-6. 1994
    ..Thus, PHAS-I may be a key mediator of the stimulation of protein synthesis by the diverse group of agents and stimuli that activate MAP kinase...
  3. doi Molecular mechanisms of mTOR-mediated translational control
    Xiaoju Max Ma
    Department of Research Oncology Diagnostics, Genentech Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nat Rev Mol Cell Biol 10:307-18. 2009
    ..Here, we highlight recent findings on the regulators and effectors of mTOR and discuss specific cases that serve as paradigms for the different modes of mTOR regulation and its control of translation...
  4. pmc Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism
    A C Gingras
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, H3G 1Y6, Canada
    Genes Dev 13:1422-37. 1999
    ..Taken together, our results suggest that 4E-BP1 phosphorylation by FRAP/mTOR on Thr-37 and Thr-46 is a priming event for subsequent phosphorylation of the carboxy-terminal serum-sensitive sites...
  5. ncbi Dissociation of the eukaryotic initiation factor-4E/4E-BP1 complex involves phosphorylation of 4E-BP1 by an mTOR-associated kinase
    K J Heesom
    Department of Biochemistry, School of Medical Sciences, University Walk, Bristol, UK
    FEBS Lett 457:489-93. 1999
    ..This phosphorylation, which occurs predominantly on S(64), results in the dissociation of 4E-BP1 from eIF-4E...
  6. pmc Distinct signaling events downstream of mTOR cooperate to mediate the effects of amino acids and insulin on initiation factor 4E-binding proteins
    Xuemin Wang
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dow St, Dundee DD1 5EH, United Kingdom
    Mol Cell Biol 25:2558-72. 2005
    ..These data have important implications for understanding signaling downstream of mTOR and the development of new strategies to impair mTOR signaling...
  7. doi 4-Nonylphenol induces autophagy and attenuates mTOR-p70S6K/4EBP1 signaling by modulating AMPK activation in Sertoli cells
    Peng Duan
    MOE Ministry of Education key lab of Environment and Health, Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China Research Center for Environment and Health, Hubei University of Medicine, Shiyan 442000, China
    Toxicol Lett . 2016
    ....
  8. doi mTOR/P70S6K promotes spermatogonia proliferation and spermatogenesis in Sprague Dawley rats
    Hao Xu
    Department of Paediatric Research Institute, Children s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
    Reprod Biomed Online 32:207-17. 2016
    ..Therefore, we suggest that mTOR plays an important role in spermatogenesis by regulating p70s6k activation and that 4e-bp1 is either directly or indirectly regulated by PI3K. ..
  9. pmc Rotenone induction of hydrogen peroxide inhibits mTOR-mediated S6K1 and 4E-BP1/eIF4E pathways, leading to neuronal apoptosis
    Qian Zhou
    Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Jiangsu Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University, Nanjing 210023, P R China, Department of Biochemistry and Molecular Biology and Feist Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130 3932
    Toxicol Sci 143:81-96. 2015
    ..Our findings suggest that rotenone-induced neuronal loss in PD may be prevented by activating mTOR signaling and/or administering antioxidants...
  10. doi Everolimus sensitizes Ras-transformed cells to radiation in vitro through the autophagy pathway
    Yu Chieh Su
    Department of Hematological Oncology, Buddhist Dalin Tzu Chi Hospital, Chiayi 62247, Taiwan, R O C
    Int J Mol Med 34:1417-22. 2014
    ..Everolimus-mediated radiosensitization is associated with the autophagy pathway. Thus, everolimus is a novel radiosensitizing agent with potential for use in cancer radiotherapy...
  11. pmc Characterization of the Raptor/4E-BP1 interaction by chemical cross-linking coupled with mass spectrometry analysis
    Kimberly Coffman
    From the Department of Microbiology, Immunology, and Molecular Genetics, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, University of California, Los Angeles, California 90095
    J Biol Chem 289:4723-34. 2014
    ..Furthermore, mutations of residues in the RCR decrease the ability of 4E-BP1 to serve as a substrate for mTORC1 in vitro and in vivo. ..
  12. ncbi Prolactin activates mammalian target-of-rapamycin through phosphatidylinositol 3-kinase and stimulates phosphorylation of p70S6K and 4E-binding protein-1 in lymphoma cells
    Jessica D Bishop
    Department of Biochemistry and Molecular Biology, Dalhousie University, 5850 College Street, Halifax, Nova Scotia, B3H 1X5 Canada
    J Endocrinol 190:307-12. 2006
    ..In summary, PRL-stimulated phosphorylation of mTOR is mediated by PI3K. PRL-activated mTOR may phosphorylate p70S6K and 4E-BP1 by restraining PP2A...
  13. ncbi Inhibition of Cap-initiation complexes linked to a novel mechanism of eIF4G depletion in acute myocardial ischemia
    E P Connolly
    Department of Microbiology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
    Cell Death Differ 13:1586-94. 2006
    ..Acute heart ischemia therefore downregulates cap-dependent translation through eIF4E sequestration triggered by eIF4G depletion...
  14. ncbi 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...
  15. ncbi Phosphorylation of PHAS-I by mitogen-activated protein (MAP) kinase. Identification of a site phosphorylated by MAP kinase in vitro and in response to insulin in rat adipocytes
    T A Haystead
    Department of Pharmacology, University of Virginia School of Medicine, Charlottesville 22903
    J Biol Chem 269:23185-91. 1994
    ..We conclude that PHAS-I is a substrate for MAP kinase both in vivo and in vitro. As PHAS-I is one of the most prominent insulin-stimulated phosphoproteins in adipocytes, it may qualify as the major MAP kinase substrate in these cells...
  16. ncbi Identification of phosphorylation sites in the translational regulator, PHAS-I, that are controlled by insulin and rapamycin in rat adipocytes
    P Fadden
    Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
    J Biol Chem 272:10240-7. 1997
    ..All five sites identified fit a (Ser/Thr)-Pro motif, suggesting that the phosphorylation of PHAS-I in cells is mediated by a proline-directed protein kinase...
  17. ncbi Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin
    G J Brunn
    Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
    Science 277:99-101. 1997
    ..These studies define a role for mTOR in translational control and offer further insights into the mechanism whereby rapamycin inhibits G1-phase progression in mammalian cells...
  18. pmc Caspase cleavage of initiation factor 4E-binding protein 1 yields a dominant inhibitor of cap-dependent translation and reveals a novel regulatory motif
    Andrew R Tee
    Division of Molecular Physiology, School of Life Sciences, Medical Sciences Institute, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
    Mol Cell Biol 22:1674-83. 2002
    ..This suggests that the N-terminal sequence of 4E-BP1 is required for optimal regulation of 4E-BPs by insulin...
  19. pmc The C-terminal residues of Saccharomyces cerevisiae Mec1 are required for its localization, stability, and function
    Lance F Dasilva
    Department of Biochemistry, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Canada N6A5C1
    G3 (Bethesda) 3:1661-74. 2013
    ..Our study supports a role for the C-terminus in Mec1 folding and stability, and suggests a role for the proteasome in regulating Mec1 levels. ..
  20. ncbi Aberrant expression and phosphorylation of 4E-BP1, a main target of mTOR signaling, in rat mammary carcinomas: an association with etiology
    Masaru Takabatake
    Radiobiology for Children s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4 9 1 Anagawa, Inage Ku, Chiba 263 8555, Japan
    In Vivo 25:853-60. 2011
    ....
  21. ncbi Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1
    D Q Yang
    Department of Hematology Oncology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105 2794, USA
    Nat Cell Biol 2:893-8. 2000
    ..Through this mechanism, a lack of ATM activity probably contributes to some of the metabolic abnormalities, such as poor growth and insulin resistance, reported in ataxia telangiectasia cells and patients with ataxia telangiectasia...
  22. ncbi Hypoxia increases the association of 4E-binding protein 1 with the initiation factor 4E in isolated rat hepatocytes
    S A Tinton
    Unité de Biochimie Toxicologique et Cancérologique, Universite Catholique de Louvain, Brussels, Belgium
    FEBS Lett 446:55-9. 1999
    ..Although hypoxia might be signalling via the rapamycin-sensitive pathway by changing eIF-4E availability, such a pathway is unlikely to be responsible for the depression in overall protein synthesis under hypoxia...
  23. ncbi Administration of triiodo-L-thyronine into dorsal hippocampus alters phosphorylation of Akt, mammalian target of rapamycin, p70S6 kinase and 4E-BP1 in rats
    Li Sui
    Institute of Neurobiology, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China
    Neurochem Res 33:1065-76. 2008
    ....
  24. ncbi Control of PHAS-I by insulin in 3T3-L1 adipocytes. Synthesis, degradation, and phosphorylation by a rapamycin-sensitive and mitogen-activated protein kinase-independent pathway
    T A Lin
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 270:18531-8. 1995
    ..Rapamycin may inhibit translation initiation by increasing PHAS-I binding to eIF-4E...
  25. doi AMPK activation attenuates S6K1, 4E-BP1, and eEF2 signaling responses to high-frequency electrically stimulated skeletal muscle contractions
    David M Thomson
    Human Performance Laboratory, Department of Exercise and Sport Science, East Carolina University, Greenville, NC 27858, USA
    J Appl Physiol (1985) 104:625-32. 2008
    ....
  26. doi Nitric oxide mediates NMDA-induced persistent inhibition of protein synthesis through dephosphorylation of eukaryotic initiation factor 4E-binding protein 1 and eukaryotic initiation factor 4G proteolysis
    Valerie Petegnief
    Departamento de Isquemia Cerebral y Neurodegeneración, Instituto de Investigaciones Biomédicas de Barcelona, CSIC IDIBAPS, Rossello 161, Barcelona 08036, Spain
    Biochem J 411:667-77. 2008
    ..In conclusion, our data show that NO mediates NMDA-induced persistent translation inhibition and suggest that deficient eIF4F activity contributes to this process...
  27. doi Global and gene-specific translational regulation in rat lung development
    Gail Otulakowski
    Program in Physiology and Experimental Medicine, Hospital for Sick Children Research Institute, 555 University Avenue, Toronto, ON M5G1X8, Canada
    Am J Respir Cell Mol Biol 40:555-67. 2009
    ..Translational regulation of IL-18 and protein phosphatase 1 regulatory (inhibitor) subunit 2 is gene-specific, as these changes contrast with the corresponding global changes in polysome abundance...
  28. pmc Expression and distribution of mTOR, p70S6K, 4E-BP1, and their phosphorylated counterparts in rat dorsal root ganglion and spinal cord dorsal horn
    Ji Tain Xu
    Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Brain Res 1336:46-57. 2010
    ..Our findings support the view that mTOR and its downstream effectors do not play a key role in acute pain...
  29. pmc New hierarchical phosphorylation pathway of the translational repressor eIF4E-binding protein 1 (4E-BP1) in ischemia-reperfusion stress
    María I Ayuso
    Department of Investigation, Hospital Ramon y Cajal, 28034 Madrid, Spain
    J Biol Chem 285:34355-63. 2010
    ..These data help to elucidate the physiological role of 4E-BP1 phosphorylation in controlling protein synthesis...
  30. ncbi Effect of quality and quantity of dietary protein on 4E-BP1 and S6K1 phosphorylation of brains in aged rats
    Miho Ohsumi
    Laboratory of Nutritional Biochemistry, School of Food and Nutritional Sciences, COE Program in the 21st Century, The University of Shizuoka, Suruga, Japan
    J Nutr Sci Vitaminol (Tokyo) 56:319-25. 2010
    ..The results suggest that the ingestion of a higher quality and quantity of dietary protein stimulates the phosphorylation of 4E-BP1 and S6K1 in the brain and increases the brain protein synthesis in the aged rats...
  31. pmc Molecular cloning and tissue distribution of PHAS-I, an intracellular target for insulin and growth factors
    C Hu
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110
    Proc Natl Acad Sci U S A 91:3730-4. 1994
    ..However, in view of its tissue distribution and the fact that the protein is phosphorylated in response to insulin, we speculate that PHAS-I is important in insulin action...
  32. ncbi The endoplasmic reticulum stress-inducible protein Niban regulates eIF2alpha and S6K1/4E-BP1 phosphorylation
    Guo Dong Sun
    Department of Pathology and Oncology, Juntendo University School of Medicine, 2 1 1 Hongo, Tokyo 113 8421, Japan
    Biochem Biophys Res Commun 360:181-7. 2007
    ..Additionally, suppression of NIBAN expression in HeLa cells promoted apoptosis. Together these results suggest that Niban is involved in the ER stress response, and that Niban can modulate cell death signaling by regulating translation...
  33. pmc Cytoplasmic-nuclear shuttling of FKBP12-rapamycin-associated protein is involved in rapamycin-sensitive signaling and translation initiation
    J E Kim
    Department of Cell and Structural Biology, University of Illinois at Urbana Champaign, 601 South Goodwin Avenue, B107, Urbana, IL 61801, USA
    Proc Natl Acad Sci U S A 97:14340-5. 2000
    ..These findings uncover a function for the nucleus in the direct regulation of the protein synthesis machinery via extracellular signals...
  34. ncbi Role of insulin, adipocyte hormones, and nutrient-sensing pathways in regulating fuel metabolism and energy homeostasis: a nutritional perspective of diabetes, obesity, and cancer
    Stephen Marshall
    Hexos Inc, 18304 NE 153rd Street, Woodinville, WA 98072, USA
    Sci STKE 2006:re7. 2006
    ....
  35. ncbi Age-associated decrease in contraction-induced activation of downstream targets of Akt/mTor signaling in skeletal muscle
    Katsuhiko Funai
    Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington St, Boston, MA 02111, USA
    Am J Physiol Regul Integr Comp Physiol 290:R1080-6. 2006
    ..These observations suggest that the anabolic response to muscle stimulation is attenuated with aging and may contribute to the limited capacity of hypertrophy in aged animals...
  36. ncbi Effect of leptin on liver alcohol dehydrogenase
    Esteban Mezey
    Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 2195, USA
    Biochem Biophys Res Commun 337:1324-9. 2005
    ..The effect of leptin in enhancing translational initiating factors may be of significance in the regulation not only of ADH but also of many other proteins...
  37. ncbi IGF-I activates the eIF4F system in cardiac muscle in vivo
    Thomas C Vary
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Pennsylvania 17033, USA
    Mol Cell Biochem 272:209-20. 2005
    ..Furthermore, the results are consistent with a role for assembly of active eIF4G.eIF4E complex and activation of S6K1 in mediating the stimulation of mRNA translation initiation by IGF-I through a PKB/mTOR signaling pathway...
  38. ncbi N-acetyl-cysteine abolishes hydrogen peroxide-induced modification of eukaryotic initiation factor 4F activity via distinct signalling pathways
    A O'Loghlen
    Servicio de Bioquimica, Departamento de Investigacion, Hospital Ramon y Cajal, Ctra Colmenar Km 9, 28034 Madrid, Spain
    Cell Signal 18:21-31. 2006
    ..Altogether our findings suggest that the effects caused by oxidative stress on eIF4s factors depends on two MAP kinase-independent signal transduction pathways, being at least one of them rapamycin-dependent...
  39. ncbi Endotoxin (LPS) stimulates 4E-BP1/PHAS-I phosphorylation in macrophages
    M W Potter
    Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Surg Res 97:54-9. 2001
    ..Translation initiation can be prevented by small 4E-binding proteins (4E-BP1 or PHAS-I) which must be phosphorylated in order to disengage eIF-4E. We examined whether LPS alters 4E-BP1 phosphorylation in macrophages...
  40. ncbi 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...
  41. ncbi Endotoxin disrupts the leucine-signaling pathway involving phosphorylation of mTOR, 4E-BP1, and S6K1 in skeletal muscle
    Charles H Lang
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Cell Physiol 203:144-55. 2005
    ..Hence, LPS working via a glucocorticoid-independent mechanism produces a leucine resistance in skeletal muscle that might be expected to impair the ability of this amino acid to stimulate translation initiation and protein synthesis...
  42. ncbi Acute alcohol intoxication enhances myocardial eIF4G phosphorylation despite reducing mTOR signaling
    Thomas C Vary
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, H166, 500 Univ Dr, Hershey, PA 17033, USA
    Am J Physiol Heart Circ Physiol 288:H121-8. 2005
    ..eIF4E complex formation, which appear to be independent of changes in phosphorylation of eIF4G but dependent on mTOR...
  43. ncbi Polyamines regulate eukaryotic initiation factor 4E-binding protein 1 gene transcription
    A H Stephenson
    Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
    Biochem Biophys Res Commun 323:204-12. 2004
    ..These data provide a mechanism by which polyamines affect transcription of the 4E-BP1 gene, which in turn affect translation of ODC and perhaps other cap-dependent proteins...
  44. ncbi Arginine and Leucine regulate p70 S6 kinase and 4E-BP1 in intestinal epithelial cells
    Hidetoshi Ban
    Department of Gastroenterological Surgery, Transplant, and Surgical Oncology, Graduate School of Medicine and Dentistry, Okayama University, Okayama 700 8558, Japan
    Int J Mol Med 13:537-43. 2004
    ..In conclusion, l-Arginine regulates p70 S6 kinase activity and phosphorylation of 4E-BP1 through mTOR signaling pathway, which involves system y(+), cationic amino acid transporters...
  45. ncbi Activated mammalian target of rapamycin pathway in the pathogenesis of tuberous sclerosis complex renal tumors
    Heidi L Kenerson
    Department of Surgery, University of Washington, Seattle 98195, USA
    Cancer Res 62:5645-50. 2002
    ..Our data provide in vivo evidence that the mTOR pathway is aberrantly activated in TSC renal pathology and that treatment with rapamycin appears effective in the preclinical setting...

Research Grants6

  1. Alcohol-Induced Regulation of Hepatic Protein Synthesis
    THOMAS VARY; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  2. EFFECTS OF ALCOHOL ON MOLECULAR AND CELLULAR PATHOLOGY
    Esteban Mezey; Fiscal Year: 2008
    ..The final objective is to instill in the trainee the ability to approach original questions of research relating to the pathogenesis of damaging effects of alcoholism on the body. ..
  3. MYOCARDIAL PROTEIN SYNTHESIS AFTER ALCOHOL INTOXICATION
    Charles H Lang; Fiscal Year: 2010
    ..Overall, the research design will establish the mechanism by which myocardial protein synthesis is reduced in response to alcohol abuse. ..
  4. Antiretroviral-Induced Defects in Muscle Protein Synthesis
    Charles H Lang; Fiscal Year: 2010
    ..Such data is needed to both realize the full potential and avoid possible pitfalls of this drug in the long-term treatment of HIV-infected individuals. ..
  5. REGULATION OF PROTEIN TURNOVER IN SEPSIS
    Scot R Kimball; Fiscal Year: 2010
    ....
  6. Myocardial Protein Synthesis After Thermal Injury
    Charles Lang; Fiscal Year: 2005
    ..Overall, the research will elucidate the mechanisms by which myocardial protein synthesis is reduced after thermal injury, leading to the better understanding and treatment of the resulting cardiomyopathy. - ..