ribosomal protein s6 kinases

Summary

Summary: A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' TOP MRNAS. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.

Top Publications

  1. ncbi TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
    Ken Inoki
    Department of Biological Chemistry, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109, USA
    Nat Cell Biol 4:648-57. 2002
  2. ncbi Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway
    Brendan D Manning
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 10:151-62. 2002
  3. ncbi Hypothalamic mTOR signaling regulates food intake
    Daniela Cota
    Department of Psychiatry, University of Cincinnati, Genome Research Institute, 2170 East Galbraith Road, Cincinnati, OH 45237, USA
    Science 312:927-30. 2006
  4. ncbi mTOR Complex1-S6K1 signaling: at the crossroads of obesity, diabetes and cancer
    Stephen G Dann
    Genome Research Institute, University of Cincinnati, 2180 E Galbraith Road, Cincinnati, OH 45237, USA
    Trends Mol Med 13:252-9. 2007
  5. pmc mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells
    Mirei Murakami
    Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Nara 630 0192, Japan
    Mol Cell Biol 24:6710-8. 2004
  6. ncbi Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans
    Malene Hansen
    Department of Biochemistry and Biophysics, University of California, 600 16th Street, San Francisco, CA 94158, USA
    Aging Cell 6:95-110. 2007
  7. ncbi Oncogenic kinase signalling
    P Blume-Jensen
    The Salk Institute, Molecular and Cell Biology Laboratory, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 411:355-65. 2001
  8. ncbi Mammalian TOR: a homeostatic ATP sensor
    P B Dennis
    The Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH 4058, Basel, Switzerland
    Science 294:1102-5. 2001
  9. ncbi Role and regulation of starvation-induced autophagy in the Drosophila fat body
    Ryan C Scott
    Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis 55455 USA
    Dev Cell 7:167-78. 2004
  10. pmc Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling
    Andrew R Tee
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:13571-6. 2002

Research Grants

Detail Information

Publications242 found, 100 shown here

  1. ncbi TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
    Ken Inoki
    Department of Biological Chemistry, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109, USA
    Nat Cell Biol 4:648-57. 2002
    ..Our data indicate a molecular mechanism for TSC2 in insulin signalling, tumour suppressor functions and in the inhibition of cell growth...
  2. ncbi Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway
    Brendan D Manning
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 10:151-62. 2002
    ..Finally, we find that a tuberin mutant lacking the major PI3K-dependent phosphorylation sites can block the activation of S6K1, suggesting a means by which the PI3K-Akt pathway regulates S6K1 activity...
  3. ncbi Hypothalamic mTOR signaling regulates food intake
    Daniela Cota
    Department of Psychiatry, University of Cincinnati, Genome Research Institute, 2170 East Galbraith Road, Cincinnati, OH 45237, USA
    Science 312:927-30. 2006
    ..Thus, mTOR is a cellular fuel sensor whose hypothalamic activity is directly tied to the regulation of energy intake...
  4. ncbi mTOR Complex1-S6K1 signaling: at the crossroads of obesity, diabetes and cancer
    Stephen G Dann
    Genome Research Institute, University of Cincinnati, 2180 E Galbraith Road, Cincinnati, OH 45237, USA
    Trends Mol Med 13:252-9. 2007
    ..Thus, to orchestrate the control of homeostatic responses, mTOR Complex1 must integrate signals from distinct cues. Here, we review recent findings concerning the regulation and pathophysiology associated with mTOR Complex1 and S6K1...
  5. pmc mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells
    Mirei Murakami
    Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Nara 630 0192, Japan
    Mol Cell Biol 24:6710-8. 2004
    ..These data show that mTOR controls both cell size and proliferation in early mouse embryos and embryonic stem cells...
  6. ncbi Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans
    Malene Hansen
    Department of Biochemistry and Biophysics, University of California, 600 16th Street, San Francisco, CA 94158, USA
    Aging Cell 6:95-110. 2007
    ..Our findings link TOR, but not sir-2.1, to the longevity response induced by dietary restriction (DR) in C. elegans, and they suggest that neither TOR inhibition nor DR extends lifespan simply by reducing protein synthesis...
  7. ncbi Oncogenic kinase signalling
    P Blume-Jensen
    The Salk Institute, Molecular and Cell Biology Laboratory, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 411:355-65. 2001
    ....
  8. ncbi Mammalian TOR: a homeostatic ATP sensor
    P B Dennis
    The Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH 4058, Basel, Switzerland
    Science 294:1102-5. 2001
    ..Here we demonstrate that the mTOR pathway is influenced by the intracellular concentration of ATP, independent of the abundance of amino acids, and that mTOR itself is an ATP sensor...
  9. ncbi Role and regulation of starvation-induced autophagy in the Drosophila fat body
    Ryan C Scott
    Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis 55455 USA
    Dev Cell 7:167-78. 2004
    ..Thus, in cells lacking TOR, autophagy plays a protective role that is dominant over its potential role as a growth suppressor...
  10. pmc Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling
    Andrew R Tee
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:13571-6. 2002
    ....
  11. pmc Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex
    James Brugarolas
    Dana Farber Cancer Institute and Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Genes Dev 18:2893-904. 2004
    ..Inhibition of mTOR function by hypoxia is likely to be important for tumor suppression as TSC2-deficient cells maintain abnormally high levels of cell proliferation under hypoxia...
  12. pmc Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway
    Pankaj Kapahi
    Division of Biology 156 29, California Institute of Technology, Pasadena, CA 91125, USA
    Curr Biol 14:885-90. 2004
    ..Modulation of expression in the fat is sufficient for the lifespan-extension effects. The lifespan extensions are dependent on nutritional condition, suggesting a possible link between the TOR pathway and dietary restriction...
  13. ncbi Phosphorylation and activation of p70s6k by PDK1
    N Pullen
    Friedrich Miescher Institute, Maulbeerstrasse 66, CH 4058, Basel, Switzerland
    Science 279:707-10. 1998
    ..More importantly, PDK1 activated p70s6k in vitro and in vivo, whereas the catalytically inactive PDK1 blocked insulin-induced activation of p70s6k...
  14. pmc Regulation of cellular growth by the Drosophila target of rapamycin dTOR
    H Zhang
    Chiron Corporation, Emeryville, California 94608, USA
    Genes Dev 14:2712-24. 2000
    ..Our results suggest that dTOR regulates growth during animal development by coupling growth factor signaling to nutrient availability...
  15. pmc The TSC1-TSC2 complex: a molecular switchboard controlling cell growth
    Jingxiang Huang
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    Biochem J 412:179-90. 2008
    ..In the present review we focus on the molecular details of TSC1-TSC2 complex regulation and function as it relates to the control of Rheb and mTORC1...
  16. pmc Receptor-recognized α₂-macroglobulin binds to cell surface-associated GRP78 and activates mTORC1 and mTORC2 signaling in prostate cancer cells
    Uma K Misra
    Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America
    PLoS ONE 7:e51735. 2012
    ..We have studied the role of α(2)M* in the regulation of mTORC1 and TORC2 signaling in the growth of human prostate cancer cells...
  17. pmc Regulation of mTORC1 and mTORC2 complex assembly by phosphatidic acid: competition with rapamycin
    Alfredo Toschi
    Department of Biological Sciences, Hunter College of the City University of New York, New York, NY 10065, USA
    Mol Cell Biol 29:1411-20. 2009
    ..This study also suggests that by suppressing PLD activity, mTORC2 could be targeted therapeutically with rapamycin...
  18. pmc Rapamycin inhibition of the Akt/mTOR pathway blocks select stages of VEGF-A164-driven angiogenesis, in part by blocking S6Kinase
    Qi Xue
    Center for Vascular Biology and the Department of Pathology at the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Arterioscler Thromb Vasc Biol 29:1172-8. 2009
    ..We evaluated the stages of VEGF-A(164) driven angiogenesis that are inhibited by therapeutic doses of rapamycin and the potential role of S6K1 in that response...
  19. ncbi Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression
    Diane C Fingar
    Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA
    Oncogene 23:3151-71. 2004
    ..In mammals, TOR is best known to regulate translation through the ribosomal protein S6 kinases (S6Ks) and the eukaryotic translation initiation factor 4E-binding proteins...
  20. pmc The PIF-binding pocket in PDK1 is essential for activation of S6K and SGK, but not PKB
    R M Biondi
    Division of Signal Transduction Therapy, MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    EMBO J 20:4380-90. 2001
    ..The PIF-binding pocket represents a substrate recognition site on a protein kinase that is only required for the phosphorylation of a subset of its physiological substrates...
  21. ncbi Temporal control of differentiation by the insulin receptor/tor pathway in Drosophila
    Joseph M Bateman
    Cancer Research UK, 44 Lincoln s Inn Fields, London, WC2A 3PX, England
    Cell 119:87-96. 2004
    ..These data suggest that intricate developmental decisions are coordinated with nutritional status and tissue growth by the InR signaling pathway...
  22. ncbi Coordinate regulation of ribosome biogenesis and function by the ribosomal protein S6 kinase, a key mediator of mTOR function
    Katarzyna Jastrzebski
    Growth Control and Differentiation Program, Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, Melbourne, Australia
    Growth Factors 25:209-26. 2007
    ..Finally, we will discuss the impact of S6K signaling and the consequent feedback regulation of the PI3K/Akt pathway on disease processes including cancer...
  23. pmc Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster
    Ivana Bjedov
    Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, UK
    Cell Metab 11:35-46. 2010
    ..Rapamycin could increase life span of weak insulin/Igf signaling (IIS) pathway mutants and of flies with life span maximized by dietary restriction, indicating additional mechanisms...
  24. pmc Complex regulation of mammalian target of rapamycin complex 1 in the basomedial hypothalamus by leptin and nutritional status
    Eneida C Villanueva
    Division of Metabolism, Department of Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
    Endocrinology 150:4541-51. 2009
    ..The regulation of mTORC1 in the basomedial hypothalamus thus varies by cell and stimulus type, as opposed to responding in a uniform manner to nutritional and hormonal perturbations...
  25. pmc Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E
    Diane C Fingar
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 16:1472-87. 2002
    ..These data show that mTOR signals downstream to at least two independent targets, S6K1 and 4EBP1/eIF4E, that function in translational control to regulate mammalian cell size...
  26. ncbi Upstream and downstream of mTOR
    Nissim Hay
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 60607, USA
    Genes Dev 18:1926-45. 2004
    ..We also summarize the roles of mTOR in the control of cell growth and proliferation, as well as its relevance to cancer and synaptic plasticity...
  27. ncbi Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome
    E Trivier
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS, INSERM, Illkirch, France
    Nature 384:567-70. 1996
    ..The mutated Rsk-2 proteins were found to be inactive in a S6 kinase assay. These findings provide direct evidence that abnormalities in the MAPK/RSK signalling pathway cause Coffin-Lowry syndrome...
  28. pmc Metabolic control by S6 kinases depends on dietary lipids
    Tamara R Castaneda
    Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Dusseldorf, Germany
    PLoS ONE 7:e32631. 2012
    ..Taken together, our results suggest that the metabolic functions of S6K in vivo play a key role as a molecular interface connecting dietary lipids to the endogenous control of energy metabolism...
  29. ncbi A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells
    David J Kwiatkowski
    Genetics Laboratory, Hematology Division, Brigham and Women s Hospital, Harvard Medical School, 221 Longwood Avenue, LM 302, Boston, MA 02115, USA
    Hum Mol Genet 11:525-34. 2002
    ..Hyperphosphorylation of S6 is also seen in kidney tumors in the heterozygote mice, suggesting that inhibition of this pathway may have benefit in control of TSC hamartomas...
  30. ncbi c-Raf/MEK/ERK pathway controls protein kinase C-mediated p70S6K activation in adult cardiac muscle cells
    Yoshihiro Iijima
    Cardiology Division of the Department of Medicine, Gazes Cardiac Research Institute, Medical University of South Carolina, Charleston, South Carolina 29425 2221, USA
    J Biol Chem 277:23065-75. 2002
    ..Together, our in vivo and in vitro studies indicate that the PKC/c-Raf/MEK/ERK pathway plays a major role in the S6K1 activation in hypertrophic cardiac growth...
  31. pmc Ligation of prostate cancer cell surface GRP78 activates a proproliferative and antiapoptotic feedback loop: a role for secreted prostate-specific antigen
    Uma K Misra
    Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 286:1248-59. 2011
    ..The present studies suggest that PSA may be involved in a signal transduction-dependent feedback loop, whereby it promotes a more aggressive behavior by human prostate cancer cells...
  32. ncbi Upregulation of mTORC2 activation by the selective agonist of EPAC, 8-CPT-2Me-cAMP, in prostate cancer cells: assembly of a multiprotein signaling complex
    Uma K Misra
    Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Cell Biochem 113:1488-500. 2012
    ....
  33. ncbi Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2
    Attila Garami
    Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
    Mol Cell 11:1457-66. 2003
    ..Finally, coexpression of a human TSC2 cDNA harboring a disease-associated point mutation in the GAP domain, failed to stimulate Rheb GTPase activity or block Rheb activation of S6K1...
  34. pmc Inhibition of S6K1 accounts partially for the anti-inflammatory effects of the arginase inhibitor L-norvaline
    Xiu Fen Ming
    Vascular Biology, Department of Medicine, Division of Physiology, University of Fribourg, Switzerland
    BMC Cardiovasc Disord 9:12. 2009
    ..We investigated whether the endothelial arginase II is involved in inflammatory responses in endothelial cells...
  35. ncbi Tuberin regulates p70 S6 kinase activation and ribosomal protein S6 phosphorylation. A role for the TSC2 tumor suppressor gene in pulmonary lymphangioleiomyomatosis (LAM)
    Elena A Goncharova
    Pulmonary, Allergy, and Critical Care Division, Department of Medicine, University of Pennsylvania, 421 Curie Boulevard, 847 BRB II III, Philadelphia, PA 19104, USA
    J Biol Chem 277:30958-67. 2002
    ..These data demonstrate that tuberin negatively regulates the activity of S6 and p70S6K specifically, and suggest a potential mechanism for abnormal cell growth in LAM...
  36. ncbi Amino acid and insulin signaling via the mTOR/p70 S6 kinase pathway. A negative feedback mechanism leading to insulin resistance in skeletal muscle cells
    F Tremblay
    Department of Physiology and Lipid Research Unit, Laval University Hospital Research Center, Ste-Foy, , Canada
    J Biol Chem 276:38052-60. 2001
    ..These results identify the mTOR/p70 S6 kinase signaling pathway as a novel modulator of insulin-stimulated glucose transport in skeletal muscle cells...
  37. pmc The Drosophila p70s6k homolog exhibits conserved regulatory elements and rapamycin sensitivity
    M J Stewart
    Friedrich Miescher Institut, Department of Growth Control, Basel, Switzerland
    Proc Natl Acad Sci U S A 93:10791-6. 1996
    ....
  38. pmc A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling
    Greg M Findlay
    Institute of Cancer Research, Cancer Research U K Centre of Cell and Molecular Biology, 237 Fulham Road, London SW3 6JB, U K
    Biochem J 403:13-20. 2007
    ..Our results therefore suggest a model whereby nutrients signal to mTORC1 via activation of MAP4K3...
  39. pmc Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR
    Hongbing Zhang
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 112:1223-33. 2003
    ..This is in contrast to PTEN, which is a negative upstream regulator of this pathway...
  40. ncbi Immunopurified mammalian target of rapamycin phosphorylates and activates p70 S6 kinase alpha in vitro
    S Isotani
    Biosignal Research Center, Kobe University, Kobe 657 8501, Japan
    J Biol Chem 274:34493-8. 1999
    ....
  41. ncbi Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins
    Yong Zhang
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 9040, USA
    Nat Cell Biol 5:578-81. 2003
    ..Point mutations in the GAP domain of Tsc2 disrupted its ability to regulate Rheb without affecting the ability of Tsc2 to form a complex with Tsc1. Our studies identify Rheb as a molecular target of the TSC tumour suppressors...
  42. pmc RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1
    P E Burnett
    Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 95:1432-7. 1998
    ..This raises the possibility that, in vivo, an unidentified kinase analogous to p70(S6k) is activated by RAFT1 phosphorylation and acts at the rapamycin-sensitive phosphorylation sites of 4E-BP1...
  43. ncbi Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms
    A Bonni
    Division of Neuroscience, Children s Hospital, and Department of Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
    Science 286:1358-62. 1999
    ....
  44. pmc Targeting protein phosphatase 1 (PP1) to the actin cytoskeleton: the neurabin I/PP1 complex regulates cell morphology
    Carey J Oliver
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Cell Biol 22:4690-701. 2002
    ..These studies provided new insights into the assembly and regulation of a neurabin I/PP1 complex that controls actin rearrangement to promote spine development in mammalian neurons...
  45. ncbi Phosphatidylinositol 3-kinase links the interleukin-2 receptor to protein kinase B and p70 S6 kinase
    K Reif
    Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    J Biol Chem 272:14426-33. 1997
    ....
  46. ncbi Regulation of thrombin-induced stress fibre formation in Swiss 3T3 cells by the 70-kDa S6 kinase
    M F Crouch
    Molecular Signalling Group, John Curtin School of Medical Research, Australian National University, Canberra, ACT
    Biochem Biophys Res Commun 233:193-9. 1997
    ..Thrombin is also shown to stimulate p70s6k activity and that this is inhibited by rapamycin. Thus, the data presented show that thrombin activates stress fibre formation through stimulation of p70s6k via a non-Gi pathway...
  47. ncbi AKT-independent phosphorylation of TSC2 and activation of mTOR and ribosomal protein S6 kinase signaling by prostaglandin F2alpha
    Edward W Arvisais
    Olson Center for Women s Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, Nebraska 68198 3255, USA
    J Biol Chem 281:26904-13. 2006
    ..The translation of proteins under the control of mTOR may have implications for luteal development and regression and offer new strategies for therapeutic intervention in PGF2alpha-target tissues...
  48. ncbi Integrin-dependent activation of the p70 ribosomal S6 kinase signaling pathway
    R K Malik
    Department of Pediatrics, Health Sciences Center, University of Virginia, Charlottesville, Virginia 22908, USA
    J Biol Chem 271:29785-91. 1996
    ..These results indicate at least a partial requirement for FAK in the S6K activation pathway...
  49. ncbi Ligand modulates VDR-Ser/Thr protein phosphatase interaction and p70S6 kinase phosphorylation in a cell-context-dependent manner
    David J Bettoun
    Inflammation, Immunomodulation, Gene Regulation and Bone Research, Indianapolis, IN 46285, USA
    J Steroid Biochem Mol Biol 89:195-8. 2004
    ....
  50. pmc Genetic and biochemical characterization of dTOR, the Drosophila homolog of the target of rapamycin
    S Oldham
    Zoologisches Institut, Universitat Zurich, 8057 Zurich, Switzerland
    Genes Dev 14:2689-94. 2000
    ..These results are consistent with dTOR residing on a parallel amino acid sensing pathway...
  51. ncbi Differential regulation of the phosphatidylinositol 3-kinase/Akt and p70 S6 kinase pathways by the alpha(1A)-adrenergic receptor in rat-1 fibroblasts
    L M Ballou
    Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284, USA
    J Biol Chem 275:4803-9. 2000
    ..Furthermore, this receptor negatively regulates the PI 3-kinase/Akt pathway, resulting in enhanced cell death following apoptotic insult...
  52. ncbi Rapamycin-induced glucose intolerance: hunger or starvation diabetes
    Mikhail V Blagosklonny
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA
    Cell Cycle 10:4217-24. 2011
    ..If rapamycin is a CR-mimetic, no wonder it may, in certain models, induce "hunger diabetes." But will rapamycin prevent true type II diabetes? Here are some answers...
  53. ncbi 14-3-3beta binds to and negatively regulates the tuberous sclerosis complex 2 (TSC2) tumor suppressor gene product, tuberin
    Stuart D Shumway
    Lineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, Program in Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, 27599 7295, USA
    J Biol Chem 278:2089-92. 2003
    ..We suggest that 14-3-3 proteins interact with the TSC1-TSC2 complex and negatively regulate the function of the TSC proteins...
  54. ncbi Insulin-like growth factor (IGF)-I regulates IGF-binding protein-5 gene expression through the phosphatidylinositol 3-kinase, protein kinase B/Akt, and p70 S6 kinase signaling pathway
    C Duan
    Department of Biology, University of Michigan, Ann Arbor, Michigan 48109 1048, USA
    J Biol Chem 274:37147-53. 1999
    ..These results suggest that the action of IGF-I on IGFBP-5 gene expression requires the activation of the PI 3-kinase-PKB/Akt-p70(s6k) pathway but not the MAPK pathway in vascular smooth muscle cells...
  55. ncbi Ligation of the alpha2M* signaling receptor regulates synthesis of cytosolic phospholipase A2
    U K Misra
    Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Arch Biochem Biophys 386:227-32. 2001
    ..We conclude that alpha2M*-induced cPLA2 synthesis is controlled by [Ca2+]i levels, tyrosine kinase activity, the p21ras-dependent MAPK and PI 3-kinase downstream signaling pathways, and regulation of NFkappaB...
  56. ncbi Mammalian target of rapamycin and S6 kinase 1 positively regulate 6-thioguanine-induced autophagy
    Xuehuo Zeng
    Department of Radiation Oncology, Case Western Reserve University, Case Comprehensive Cancer Center University Hospitals Case Medical Center, Cleveland, OH 44106 6068, USA
    Cancer Res 68:2384-90. 2008
    ..Activated Akt is a well-known inhibitor of autophagy. In conclusion, our data indicate that mTOR-S6K1 positively regulates autophagy after MMR processing of 6-TG probably through its negative feedback inhibition of Akt...
  57. pmc PDK1 regulates growth through Akt and S6K in Drosophila
    F Rintelen
    Zoologisches Institut, Universitat Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Proc Natl Acad Sci U S A 98:15020-5. 2001
    ..Thus, the results suggest that dPDK1 is required for dRSK but not dPKN activation and that it regulates insulin-mediated growth through two main effector branches, dAkt and dS6K...
  58. ncbi Hypoinsulinaemia, glucose intolerance and diminished beta-cell size in S6K1-deficient mice
    M Pende
    Friedrich Miescher Institute, Basel, Switzerland
    Nature 408:994-7. 2000
    ..The observed phenotype closely parallels those of preclinical type 2 diabetes mellitus, in which malnutrition-induced hypoinsulinaemia predisposes individuals to glucose intolerance...
  59. ncbi dS6K-regulated cell growth is dPKB/dPI(3)K-independent, but requires dPDK1
    Thomas Radimerski
    Friedrich Miescher Institute, Novartis Research Foundation, Maulbeerstrasse 66, 4058 Basel, Switzerland
    Nat Cell Biol 4:251-5. 2002
    ....
  60. ncbi mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events
    Marina K Holz
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 123:569-80. 2005
    ..Thus, the eIF3 preinitiation complex acts as a scaffold to coordinate a dynamic sequence of events in response to stimuli that promote efficient protein synthesis...
  61. ncbi Hyperbaric oxygen preconditioning activates ribosomal protein S6 kinases and reduces brain swelling after intracerebral hemorrhage
    Z Qin
    Department of Neurosurgery, Room 5018, BSRB, University of Michigan, Ann Arbor, MI 48109 2200, USA
    Acta Neurochir Suppl 102:317-20. 2008
    New protein synthesis is key to ischemic tolerance induced by preconditioning and ribosomal protein S6 kinases (p70 S6 K) are important enzymes in protein synthesis. Hyperbaric oxygen preconditioning (HBOP) reduces ischemic brain damage...
  62. pmc The AMPK agonist AICAR inhibits the growth of EGFRvIII-expressing glioblastomas by inhibiting lipogenesis
    Deliang Guo
    Department of Pathology and Laboratory Medicine, The David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 106:12932-7. 2009
    ..These results suggest a mechanism by which AICAR inhibits the proliferation of EGFRvIII expressing glioblastomas and point toward a potential therapeutic strategy for targeting EGFR-activated cancers...
  63. ncbi MAPK, phosphatidylinositol 3-kinase, and mammalian target of rapamycin pathways converge at the level of ribosomal protein S6 phosphorylation to control metabolic signaling in CD8 T cells
    Robert J Salmond
    Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom
    J Immunol 183:7388-97. 2009
    ..These results place rpS6 phosphorylation as a point of convergence for multiple crucial signaling pathways downstream of TCR triggering...
  64. pmc mTOR-dependent regulation of ribosomal gene transcription requires S6K1 and is mediated by phosphorylation of the carboxy-terminal activation domain of the nucleolar transcription factor UBF
    Katherine M Hannan
    Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, USA
    Mol Cell Biol 23:8862-77. 2003
    ..Thus, mTOR plays a critical role in the regulation of ribosome biogenesis via a mechanism that requires S6K1 activation and phosphorylation of UBF...
  65. ncbi Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3
    P Sassone-Corsi
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS, INSERM, ULP, B P 163, 67404 Illkirch Strasbourg, France
    Science 285:886-91. 1999
    ..H3 appears to be a direct or indirect target of Rsk-2, suggesting that chromatin remodeling might contribute to mitogen-activated protein kinase-regulated gene expression...
  66. pmc The immunosuppressant rapamycin mimics a starvation-like signal distinct from amino acid and glucose deprivation
    Tao Peng
    Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142, USA
    Mol Cell Biol 22:5575-84. 2002
    ..These observations underscore the importance of metabolism in controlling lymphocyte proliferation and offer a novel explanation for immunosuppression by rapamycin...
  67. pmc Disruption of the p70(s6k)/p85(s6k) gene reveals a small mouse phenotype and a new functional S6 kinase
    H Shima
    Friedrich Miescher Institute, Maulbeerstrasse 66, CH 4058 Basel, Switzerland
    EMBO J 17:6649-59. 1998
    ..The finding of a new S6 kinase gene, which can partly compensate for p70(s6k)/p85(s6k) function, underscores the importance of S6K function in cell growth...
  68. ncbi Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies
    O Jameel Shah
    Molecular and Cellular Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Curr Biol 14:1650-6. 2004
    ..Our results suggest that inappropriate activation of the Rheb/mTOR/S6K pathway imposes a negative feedback program to attenuate IRS-dependent processes such as cell survival...
  69. ncbi Transcription inhibitors stimulate translation of 5' TOP mRNAs through activation of S6 kinase and the mTOR/FRAP signalling pathway
    F Loreni
    Dipartimento di Biologia, Universita Tor Vergata, Roma, Italy Department of Growth Control, Friedrich Miescher Institut, Basel, Switzerland
    Eur J Biochem 267:6594-601. 2000
    ..Concentrations of act D sufficient to induce TOP mRNA translation also induce 40S ribosomal protein S6 kinases 1 (S6K1) activation...
  70. pmc Functional analysis of the PP2A subfamily of protein phosphatases in regulating Drosophila S6 kinase
    Vincent A Bielinski
    Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9041, USA
    Exp Cell Res 313:3117-26. 2007
    ..These results indicate that PP2A, but not other members of this subfamily, is likely to be a major S6K phosphatase in intact cells and is consistent with an important role for this phosphatase in the TOR pathway...
  71. ncbi PRAS40 is a target for mammalian target of rapamycin complex 1 and is required for signaling downstream of this complex
    Bruno D Fonseca
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 282:24514-24. 2007
    ..However, this has no effect on the phosphorylation of Akt or TSC2 (an Akt substrate). These data place PRAS40 downstream of mTORC1 but upstream of its effectors, such as S6K1 and 4E-BP1...
  72. ncbi Regulation of mammalian translation factors by nutrients
    Christopher G Proud
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, MSI WTB complex, Dow Street, UK
    Eur J Biochem 269:5338-49. 2002
    ..Since control of eIF2B is independent of mTOR, these data indicate the operation of additional, and so far unknown, regulatory mechanisms that control eIF2B activity...
  73. ncbi Targeting ribosomal S-6 kinase for the prevention and treatment of liver injury and liver fibrosis
    Martina Buck
    Moores Cancer Center, University of California, San Diego, California, USA
    Drug News Perspect 21:301-6. 2008
    ..Thus, appropriate RSK inhibitors may be beneficial in the prevention and treatment of liver injury and liver fibrosis. These issues will be discussed in this review...
  74. pmc Neurabin is a synaptic protein linking p70 S6 kinase and the neuronal cytoskeleton
    P E Burnett
    Department of Neuroscience, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 95:8351-6. 1998
    ..Subcellular fractionation of rat brain demonstrates that neurabin and p70(S6k) both localize to the soluble fraction of synaptosomes. By way of its PDZ domain, the neuronal-specific neurabin may target p70(S6k) to nerve terminals...
  75. pmc A ribosomal S-6 kinase-mediated signal to C/EBP-beta is critical for the development of liver fibrosis
    Martina Buck
    Department of Medicine and Moores Cancer Center, University of California at San Diego, La Jolla, California, United States of America
    PLoS ONE 2:e1372. 2007
    ..Here we show that activation of RSK and phosphorylation of C/EBPbeta on Thr217 in activated HSC is critical for the progression of liver fibrosis...
  76. pmc A PI3-kinase-mediated negative feedback regulates neuronal excitability
    Eric Howlett
    Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, United States of America
    PLoS Genet 4:e1000277. 2008
    ..Our work suggests that some of the deficits in these neurological disorders might result from disruption of glutamate-mediated homeostasis of neuronal excitability...
  77. 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
    Considerable biochemical and pharmacological evidence suggests that the activation of ribosomal protein S6 kinases (S6Ks) by activated receptor tyrosine kinases involves multiple co-ordinated input signals...
  78. ncbi C/EBPbeta phosphorylation by RSK creates a functional XEXD caspase inhibitory box critical for cell survival
    M Buck
    Molecular Biology and Virology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Mol Cell 8:807-16. 2001
    ..C/EBPbeta-/- and C/EBPbeta-Ala(217) stellate cells were rescued from apoptosis by the cell permeant KE(217)VD tetrapeptide or C/EBPbeta-Glu(217)...
  79. pmc Ribosomal protein S6 kinase is a critical downstream effector of the target of rapamycin complex 1 for long-term facilitation in Aplysia
    Daniel B Weatherill
    Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada
    J Biol Chem 285:12255-67. 2010
    ..Thus, we demonstrate that S6K is an important downstream target of TORC1 in Aplysia and that it is necessary for 24-h LTF, but not for TORC1-mediated increases in somatic cap-dependent translation...
  80. ncbi S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth
    N Valerio Dorrello
    Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, MSB 599, New York, NY 10016, USA
    Science 314:467-71. 2006
    ..We propose that regulated degradation of PDCD4 in response to mitogens allows efficient protein synthesis and consequently cell growth...
  81. ncbi Serotonin activates S6 kinase in a rapamycin-sensitive manner in Aplysia synaptosomes
    A Khan
    Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada
    J Neurosci 21:382-91. 2001
    ..These results suggest a mechanism by which the levels of translation factors can be increased specifically at activated synapses generating a long-lasting synaptic tag...
  82. ncbi Resveratrol suppresses angiotensin II-induced Akt/protein kinase B and p70 S6 kinase phosphorylation and subsequent hypertrophy in rat aortic smooth muscle cells
    Ursula G B Haider
    Department of Pharmacy, Center of Drug Research, University of Munich, Munich, Germany
    Mol Pharmacol 62:772-7. 2002
    ..Thus, this study delivers important new insight in the molecular pathways that may contribute to the proposed beneficial effects of RV in cardiovascular disease...
  83. pmc The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins
    Laura S Harrington
    Cancer Research UK Centre for Cell and Molecular Biology, The Institute of Cancer Research, 237 Fulham Rd, London SW3 6JB, England, UK
    J Cell Biol 166:213-23. 2004
    ..Our results argue that the low malignant potential of tumors arising from TSC1-2 dysfunction may be explained by the failure of TSC mutant cells to activate PI3K and its downstream effectors...
  84. pmc Tuberous sclerosis complex tumor suppressor-mediated S6 kinase inhibition by phosphatidylinositide-3-OH kinase is mTOR independent
    Anja Jaeschke
    Cancer Research UK Centre for Cell and Molecular Biology, Institute for Cancer Research, 237 Fulham Road, London SW3 6JB, UK
    J Cell Biol 159:217-24. 2002
    ....
  85. ncbi Drosophila S6 kinase: a regulator of cell size
    J Montagne
    Friedrich Miescher Institute, Maulbeerstrasse 66, 4058 Basel, Switzerland
    Science 285:2126-9. 1999
    ..Thus, the dS6K gene product regulates cell size in a cell-autonomous manner without impinging on cell number...
  86. pmc A phosphoserine-regulated docking site in the protein kinase RSK2 that recruits and activates PDK1
    M Frodin
    Department of Clinical Biochemistry, Glostrup Hospital, DK 2600 Glostrup, Denmark
    EMBO J 19:2924-34. 2000
    ..Our results suggest a novel regulatory mechanism based on phosphoserine-mediated recruitment of PDK1 to RSK2, leading to coordinated phosphorylation and activation of PDK1 and RSK2...
  87. pmc Renal angiomyolipomas from patients with sporadic lymphangiomyomatosis contain both neoplastic and non-neoplastic vascular structures
    Magdalena Karbowniczek
    Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Am J Pathol 162:491-500. 2003
    ..Angiomyolipomas appear to reflect novel vascular mechanisms that may be the result of activation of cellular pathways involving S6 Kinase...
  88. pmc The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in Drosophila
    Jan H Reiling
    Zoologisches Institut, Universitat Zurich, CH 8057 Zurich, Switzerland
    Genes Dev 18:2879-92. 2004
    ....
  89. ncbi Rheb is an essential regulator of S6K in controlling cell growth in Drosophila
    Hugo Stocker
    Zoologisches Institut der Universitat Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
    Nat Cell Biol 5:559-65. 2003
    ....
  90. ncbi The signal-dependent coactivator CBP is a nuclear target for pp90RSK
    T Nakajima
    Department of Cellular and Molecular Physiology Harvard Medical School Boston, Massachusetts 02115, USA
    Cell 86:465-74. 1996
    ..These results provide a demonstration of cross-coupling between two signaling pathways that occurs at the level of a signal-dependent coactivator...
  91. ncbi Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb
    Andrew R Tee
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Curr Biol 13:1259-68. 2003
    ..Tuberin and Hamartin form a tumor suppressor heterodimer that inhibits the mammalian target of rapamycin (mTOR) nutrient signaling input, but how this occurs is unclear...
  92. ncbi 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...
  93. ncbi Phosphatidylinositol 3-kinase and mTOR mediate lipopolysaccharide-stimulated nitric oxide production in macrophages via interferon-beta
    S L Weinstein
    Department of Biology, San Francisco State University, CA 94132, USA
    J Leukoc Biol 67:405-14. 2000
    ..Together, these data suggest that PI 3-kinase, mTOR, and possibly p70 S6 kinase mediate LPS-induced NO production by regulating the secretion of interferon-beta and by a second undefined mechanism...
  94. ncbi 3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro
    D R Alessi
    Department of Biochemistry, MRC Phosphorylation Unit, University of Dundee, Dundee, UK
    Curr Biol 8:69-81. 1998
    ..It is not known which protein kinases phosphorylate and activate p70...
  95. ncbi Inactivation of the tuberous sclerosis complex-1 and -2 gene products occurs by phosphoinositide 3-kinase/Akt-dependent and -independent phosphorylation of tuberin
    Andrew R Tee
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 278:37288-96. 2003
    ..This work reveals that both PI3K-independent and -dependent mechanisms modulate tuberin phosphorylation in vivo...
  96. ncbi The protein kinase p90 rsk as an essential mediator of cytostatic factor activity
    R R Bhatt
    Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA 94305 5332, USA
    Science 286:1362-5. 1999
    ..Replenishing Rsk-depleted extracts with catalytically competent Rsk protein restored the ability of the extracts to undergo mitotic arrest. Rsk appears to be essential for cytostatic factor arrest...
  97. ncbi Intracellular signaling of angiotensin II-induced p70 S6 kinase phosphorylation at Ser(411) in vascular smooth muscle cells. Possible requirement of epidermal growth factor receptor, Ras, extracellular signal-regulated kinase, and Akt
    S Eguchi
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 274:36843-51. 1999
    ....
  98. ncbi Regulation of ribosomal S6 kinase 2 by effectors of the phosphoinositide 3-kinase pathway
    K A Martin
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 276:7884-91. 2001
    ..Understanding the regulation of the two S6K homologs may provide insight into the physiological roles of these kinases...
  99. ncbi Regulation of cell size in growth, development and human disease: PI3K, PKB and S6K
    Sara C Kozma
    Friedrich Miescher Institute, Basel, Switzerland
    Bioessays 24:65-71. 2002
    ....
  100. pmc Mammalian target of rapamycin pathway regulates insulin signaling via subcellular redistribution of insulin receptor substrate 1 and integrates nutritional signals and metabolic signals of insulin
    A Takano
    First Department of Medicine, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan
    Mol Cell Biol 21:5050-62. 2001
    ..This work identifies a novel function of mTOR that integrates nutritional signals and metabolic signals of insulin...
  101. ncbi A vitamin D receptor-Ser/Thr phosphatase-p70 S6 kinase complex and modulation of its enzymatic activities by the ligand
    David J Bettoun
    Gene Regulation, Bone, and Inflammation Research, Eli Lilly and Company, Indianapolis, Indiana 46285, USA
    J Biol Chem 277:24847-50. 2002
    ..Since p70(S6k) is essential for G(1)-S transition, our results provide a molecular basis of 1alpha,25-dihydroxyvitamin D(3)-induced G(1) block in colon cancer cells...

Research Grants60

  1. Mechanisms of S6K1 Mediated Insulin Resistance
    George Thomas; Fiscal Year: 2010
    ..Thus, if S6K1 is a critical player in these diseases the development of a small molecule inhibitor to S6K1 may act to improve the quality of life of those suffering from insulin resistance. ..
  2. Metabolic Adaptive Responses in Cancer
    David R Plas; Fiscal Year: 2013
    ....
  3. Amino Acids and Muscle Protein Synthesis
    Robert Wolfe; Fiscal Year: 2006
    ..abstract_text> ..
  4. AIRWAY MYOCYTE PROLIFERATION AND LYSOSOMAL HYDROLASE
    DUKHEE LEW; Fiscal Year: 2001
    ..The proposed studies are intended to advance the knowledge of the mechanism(s) underlying airway smooth muscle proliferation. ..
  5. Alcohol-Induced Regulation of Hepatic Protein Synthesis
    THOMAS VARY; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  6. REGULATION OF PROTEIN TURNOVER IN SEPSIS
    Scot R Kimball; Fiscal Year: 2010
    ....
  7. 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. - ..
  8. 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. ..
  9. 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. ..
  10. REGULATION OF ADIPOCYTE PROTEIN SYNTHESIS BY AMINO ACIDS
    Christopher Lynch; Fiscal Year: 2007
    ..The proposed studies will elucidate how leucine regulates mTOR and the roles of leucine stimulation of mTOR in adipose tissue physiology and obesity. ..
  11. Role of Leucine Metabolism in Leucine Signaling
    CHRISTOPHER JOHN LYNCH; Fiscal Year: 2010
    ..The implication of our ongoing research is that blocking the first step in BCAA metabolism with a drug, or to a less extent increasing dietary BCAAs, will promote weight loss. ..
  12. GELSOLIN: ROLES IN APOPTOSIS AND TUMOR DEVELOPMENT
    David Kwiatkowski; Fiscal Year: 2003
    ..The results should provide major insight into the function of gelsolin in these processes and provide potential therapeutic strategies to modulate apoptosis and malignant potential. ..
  13. RESEARCH TRAINING IN PHYSIOLOGICAL ADAPTATION TO STRESS
    Leonard Jefferson; Fiscal Year: 2005
    ..abstract_text> ..
  14. GENOTYPING CENTER FOR INNATE IMMUNITY PGA
    David Kwiatkowski; Fiscal Year: 2004
    ..abstract_text> ..
  15. MURINE MODELS OF TSC 1: MECHANISMS AND THERAPIES
    David Kwiatkowski; Fiscal Year: 2001
    ....
  16. Pre-Clinical Trials of GEM Models for Gliomas
    Eric Holland; Fiscal Year: 2007
    ..abstract_text> ..
  17. Preclinical Studies of Rapamycin for TSC Brain Disease
    David Kwiatkowski; Fiscal Year: 2006
    ..These studies will provide critical preclinical data that will support the use of rapamycin or analogues in the treatment of TSC patients with cortical tubers and subependymal giant cell astrocytomas. ..
  18. INVESTIGATING THE MECHANISMS OF PRB TUMOR SUPPRESSION
    Arnab Chakravarti; Fiscal Year: 2003
    ..Specific Aim number 3: To determine whether the deregulation of E2F dependent transcription is correlated with the tumorigenic potential of RB -/- cells in-vivo. ..
  19. Mentored Patient-Oriented Research Career Development Aw
    Zhenqi Liu; Fiscal Year: 2004
    ....
  20. Tuberous Sclerosis: Mutations and Murine Models
    David Kwiatkowski; Fiscal Year: 2006
    ..Last, the in vivo interaction in the mouse between Tsc2 null alleles and null alleles for p53, p27KIP, p21CIP, Msh2, and gelsolin will be explored. ..
  21. Modeling the effects of INK4 alpha ARF loss on gliomas
    Eric Holland; Fiscal Year: 2003
    ....
  22. Regulation of Nucleoside Transporters by Protein Kinases
    Lee Graves; Fiscal Year: 2007
    ..Aim #2. Elucidate the promoter elements necessary for the expression of ENT1 and ENT2. Aim #3. Examine the specific roles of ENTs in growth, differentiation and chemosensitization . ..
  23. Regulation of long term feeding and triglyceride storage using Drosophila
    Pankaj Kapahi; Fiscal Year: 2006
    ..Our findings will significantly affect our understanding of the causes of obesity, which is a growing epidemic in the world. ..
  24. Synaptic Plasticity in the BNST and Drug Dependence
    Walter Francesconi; Fiscal Year: 2006
    ....
  25. The Role of Tuberin in Smooth Muscle Cell Proliferation
    Geraldine Finlay; Fiscal Year: 2007
    ..abstract_text> ..
  26. STAT3 in the Pathogenesis and Treatment of Pancreatic Cancer
    David Frank; Fiscal Year: 2007
    ..We will test these drugs to determine whether they can be prototypes for a novel targeted form of therapy for this disease. [unreadable] [unreadable] [unreadable]..
  27. TOR, mRNA Translation and Dietary Restriction in Drosophila
    Pankaj Kapahi; Fiscal Year: 2010
    ..Our findings will have a significant effect on understanding the role of nutrition in aging and age-related diseases in humans. ..
  28. Functional contribution of neural stem cells in stroke
    Kunlin Jin; Fiscal Year: 2010
    ..abstract_text> ..
  29. Akt, cellular senescence, and lifespan
    Nissim Hay; Fiscal Year: 2010
    ..abstract_text> ..
  30. Role of Leptin in Islet Growth
    Rohit Kulkarni; Fiscal Year: 2008
    ..The proposed studies are aimed at the long-term goal of developing therapeutic strategies to prevent or delay the development of diabetes in obese individuals. [unreadable] [unreadable] [unreadable]..
  31. IGF-I and its binding proteins in vascular smooth muscle cells
    Cunming Duan; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  32. MOLECULAR BASIS OF CELL GROWTH CONTROL BY THE TOR KINASE
    Joseph Avruch; Fiscal Year: 2011
    ..The results of these studies will provide basis for therapeutic interventions in this pathway, which is crucial to both human cancers and to diseases like Type 2 diabetes ..
  33. SH2-B regulation of body weight and energy homeostasis
    Liangyou Rui; Fiscal Year: 2010
    ..3. Determine whether SH2-B differentially regulates leptin sensitivity in the LEPRb-neurons governing energy intake versus energy expenditure. ..
  34. Antigen specific modeling of glioma immunotherapy
    Andrew Parsa; Fiscal Year: 2007
    ..The long-term goal of this proposal is to facilitate the development of Dr. Parsa into an independent investigator capable of making meaningful scientific contributions. ..
  35. Renal Cell Injury in Diabetes
    Karen Block; Fiscal Year: 2008
    ..Elucidating these events may allow future modulation of the enzymatic complex(es) to prevent oxidative stress implicated in cellular injury in diabetes. [unreadable] [unreadable]..
  36. Ethanol and cholesterol homeostasis in the brain
    Marina Guizzetti; Fiscal Year: 2006
    ..abstract_text> ..
  37. CNS Effects of Alcohol-Gene Expression
    Pietro Sanna; Fiscal Year: 2006
    ..abstract_text> ..
  38. S6 Phosphorylation & Tyrosine Protein Kinases
    JAMES MALLER; Fiscal Year: 2004
    ..Experiments will evaluate whether Bub1 mediates CSF arrest by the MAPK pathway. This work provides a link between the MAPK/Rsk pathway and checkpoint control of the cell cycle at the metaphase/anaphase transition. ..
  39. REGULATION OF CARBAMYL PHOSPH SYNTHETASES BY MAP KINASE
    Lee Graves; Fiscal Year: 2002
    ..Eventually with the design of potent and selective inhibitors of growth factor-activated kinase signaling pathways, novel strategies for the regulation of nucleotide metabolism and cell growth may be achieved. ..
  40. Cellular Mechanisms of HIV-induced Cognitive Deficits
    Pietro Sanna; Fiscal Year: 2003
    ..Such an observation would support a crucial role for this viral product in the cognitive dysfunction of HIV-infected individuals. The results of the proposed study will advance the understanding of the pathogenesis of HAD. ..
  41. CONTROL OF CELL DIVISION IN XENOPUS OOCYTES
    JAMES MALLER; Fiscal Year: 2003
    ..Further work will examine the regulation, localization, and targets of PIx1 and identify kinases that activate xPIkk1. ..
  42. FOCAL ADHESION KINASE SIGNALING
    J Parsons; Fiscal Year: 2003
    ..abstract_text> ..
  43. STAT SIGNALING IN CHRONIC LYMPHOCYTIC LEUKEMIA
    David Frank; Fiscal Year: 2003
    ..As a result of these experiments, we plan to discern the role of STATs in the abnormal growth of CLL cells, and to identify targets for novel and specific therapies. ..
  44. TRANSLATIONAL CONTROL MEDIATED BY MRNA STRUCTURE
    Marilyn Kozak; Fiscal Year: 2002
    ..The reason why 40S ribosome/factor complexes protect "extra" sequences, which are accessible to RNase in 80S initiation complexes, will be studied. ..
  45. BROWN FAT AND THE CENTRAL CONTROL OF ENERGY BALANCE
    JEFFREY FLIER; Fiscal Year: 2002
    ..In the fourth aim, the investigators will use transgenic and gene targeting approaches involving several of these genes to ask questions about the mechanisms by which they function together to regulate energy balance. ..
  46. Role of SH2-B in signaling by leptin and insulin
    Liangyou Rui; Fiscal Year: 2002
    ..These studies will reveal the role of SH2-B in leptin and insulin signaling, and might identify new targets (e.g. SH2-B and it associated pathways) for therapeutic interventions of obesity and type 2 diabetes. ..
  47. Molecular Signaling of Rapamycin Induced Hyperlipidemia
    GHADA SOLIMAN; Fiscal Year: 2004
    ..Findings from these studies will identify the intermediate molecules altered by rapamycin and will address the cross-talk between mTOR and insulin signaling. ..
  48. INSULIN & GLUCOSE SIGNALING PATHWAYS IN ISLET BETA CELLS
    Rohit Kulkarni; Fiscal Year: 2004
    ....
  49. Role of proteoglycans in cocaine dependence
    Pietro Sanna; Fiscal Year: 2004
    ..The elucidation of the neurobiological bases for the transition from non-dependent drug use to addiction is of crucial importance for the development of novel and more effective therapeutic approaches. ..
  50. Alcohol Availability, Alcohol Use and Child Maltreatment
    Bridget Freisthler; Fiscal Year: 2006
    ..This study also will yield a dataset with contextual factors from the 2000 census and alcohol outlet density variables that can be analyzed with Add Health interview data by other investigators. ..
  51. High Throughput Screening for Modulators of STAT5 (RMI)
    David Frank; Fiscal Year: 2004
    ..The ultimate goal is the development of compounds that will act as targeted therapies for human cancers. ..
  52. Effects of Alcohol on the BNST-Cellular Neurobiology
    Pietro Sanna; Fiscal Year: 2005
    ..abstract_text> ..
  53. Dissecting the Death Pathway in Islet Beta Cells
    Rohit Kulkarni; Fiscal Year: 2005
    ..abstract_text> ..
  54. Recombinant Antibodies for Neonatal HSV Prophylaxis
    Pietro Sanna; Fiscal Year: 2005
    ....
  55. Function of Cortactin, a Src Target
    J Parsons; Fiscal Year: 2005
    ..Such mice, bearing a mutated form of Cortactin will allow one to directly test the role of Cortactin in mediating specific cellular functions in a cell type specific fashion. ..
  56. GENETIC TRACING STRATEGIES FOR THE RAT NERVOUS SYSTEM
    Pietro Sanna; Fiscal Year: 2005
    ..The results of the present R21 will contribute to the development and refinement of strategies for the regulated delivery of recombinant tracers and, in follow-up studies, other reporters such as functional biosensors. ..
  57. Leptin modulation of insulin action in the islet b-cell
    Rohit Kulkarni; Fiscal Year: 2005
    ..abstract_text> ..
  58. Analysis of MAPK in Memory Formation.
    Justin Shobe; Fiscal Year: 2004
    ..Two hypotheses will be tested: (1) That calcium dependent MAPK activation is specifically required for activity-dependent ITF and ITM, and (2) that persistent MAPK activation is selectively recruited for the induction of LTF and LTM. ..
  59. PI3-kinase and mTOR in NO production by macrophages
    STEVE WEINSTEIN; Fiscal Year: 2002
    ..The activity of p70 S6 kinase will be perturbed with a transfected mutant p70 S6 kinase allele and the consequence of this manipulation on the synthesis of interferon-beta and NO will be determined. ..