glycogen synthase kinase 3

Summary

Summary: A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.

Top Publications

  1. pmc GSK-3: tricks of the trade for a multi-tasking kinase
    Bradley W Doble
    Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada
    J Cell Sci 116:1175-86. 2003
  2. ncbi The ground state of embryonic stem cell self-renewal
    Qi Long Ying
    Center for Stem Cell and Regenerative Medicine, Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, 1501 San Pablo Street, ZNI 529, Los Angeles, California 90033, USA
    Nature 453:519-23. 2008
  3. ncbi Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
    D A Cross
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK
    Nature 378:785-9. 1995
  4. ncbi Wnt signaling and cancer
    P Polakis
    Department of Molecular Oncology, Genentech Inc, South San Francisco, California 94080 USA
    Genes Dev 14:1837-51. 2000
  5. ncbi Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor
    Noboru Sato
    Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Nat Med 10:55-63. 2004
  6. pmc Inhibition of glycogen synthase kinase-3 alleviates Tcf3 repression of the pluripotency network and increases embryonic stem cell resistance to differentiation
    Jason Wray
    Wellcome Trust Centre for Stem Cell Research and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK
    Nat Cell Biol 13:838-45. 2011
  7. pmc beta-catenin is a target for the ubiquitin-proteasome pathway
    H Aberle
    Max Planck Institute for Immunobiology, Department of Molecular Embryology, Freiburg, Germany
    EMBO J 16:3797-804. 1997
  8. ncbi Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism
    Chunming Liu
    Division of Neuroscience, Children s Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
    Cell 108:837-47. 2002
  9. ncbi The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling
    C A Grimes
    Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Sparks Center 1057, Birmingham, AL 35294-0017, USA
    Prog Neurobiol 65:391-426. 2001
  10. ncbi The glamour and gloom of glycogen synthase kinase-3
    Richard S Jope
    Department of Psychiatry and Behavioral Neurobiology, Sparks Center 1057, University of Alabama at Birmingham, Birmingham, AL 35294 0017, USA
    Trends Biochem Sci 29:95-102. 2004

Detail Information

Publications339 found, 100 shown here

  1. pmc GSK-3: tricks of the trade for a multi-tasking kinase
    Bradley W Doble
    Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada
    J Cell Sci 116:1175-86. 2003
    b>Glycogen synthase kinase 3 (GSK-3) is a multifunctional serine/threonine kinase found in all eukaryotes...
  2. ncbi The ground state of embryonic stem cell self-renewal
    Qi Long Ying
    Center for Stem Cell and Regenerative Medicine, Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, 1501 San Pablo Street, ZNI 529, Los Angeles, California 90033, USA
    Nature 453:519-23. 2008
    ..Additional inhibition of glycogen synthase kinase 3 consolidates biosynthetic capacity and suppresses residual differentiation...
  3. ncbi Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
    D A Cross
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK
    Nature 378:785-9. 1995
    ..Like the inhibition of GSK3 (refs 10, 14), the activation of PKB is prevented by inhibitors of phosphatidylinositol (PI) 3-kinase...
  4. ncbi Wnt signaling and cancer
    P Polakis
    Department of Molecular Oncology, Genentech Inc, South San Francisco, California 94080 USA
    Genes Dev 14:1837-51. 2000
  5. ncbi Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor
    Noboru Sato
    Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Nat Med 10:55-63. 2004
    ..These results suggest that the use of GSK-3-specific inhibitors such as BIO may have practical applications in regenerative medicine...
  6. pmc Inhibition of glycogen synthase kinase-3 alleviates Tcf3 repression of the pluripotency network and increases embryonic stem cell resistance to differentiation
    Jason Wray
    Wellcome Trust Centre for Stem Cell Research and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK
    Nat Cell Biol 13:838-45. 2011
    ..We conclude that Gsk3 inhibition stabilizes the embryonic stem cell state primarily by reducing repressive influence on the core pluripotency network...
  7. pmc beta-catenin is a target for the ubiquitin-proteasome pathway
    H Aberle
    Max Planck Institute for Immunobiology, Department of Molecular Embryology, Freiburg, Germany
    EMBO J 16:3797-804. 1997
    ..We show that ubiquitination of beta-catenin is greatly reduced in Wnt-expressing cells, providing the first evidence that the ubiquitin-proteasome degradation pathway may act downstream of GSK3beta in the regulation of beta-catenin...
  8. ncbi Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism
    Chunming Liu
    Division of Neuroscience, Children s Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
    Cell 108:837-47. 2002
    ..Our study uncovers distinct roles and steps of beta-catenin phosphorylation, identifies CKIalpha as a component in Wnt/beta-catenin signaling, and has implications to pathogenesis/therapeutics of human cancers and diabetes...
  9. ncbi The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling
    C A Grimes
    Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Sparks Center 1057, Birmingham, AL 35294-0017, USA
    Prog Neurobiol 65:391-426. 2001
    ..Thus, GSK3beta has a central role regulating neuronal plasticity, gene expression, and cell survival, and may be a key component of certain psychiatric and neurodegenerative diseases...
  10. ncbi The glamour and gloom of glycogen synthase kinase-3
    Richard S Jope
    Department of Psychiatry and Behavioral Neurobiology, Sparks Center 1057, University of Alabama at Birmingham, Birmingham, AL 35294 0017, USA
    Trends Biochem Sci 29:95-102. 2004
    ..Therefore, much effort is currently directed towards understanding the functions and control of GSK3, and identifying methods capable of diminishing the deleterious impact of GSK3 in pathological conditions...
  11. ncbi Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1
    Ulrich Maurer
    Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, California 92121, USA
    Mol Cell 21:749-60. 2006
    ..The results demonstrate that the control of MCL-1 stability by GSK-3 is an important mechanism for the regulation of apoptosis by growth factors, PI3K, and AKT...
  12. pmc GSK3: a multifaceted kinase in Wnt signaling
    Dianqing Wu
    Vascular Biology and Therapeutics Program and Department of Pharmacology, Yale University School of Medicine, New Haven, CT 065202, USA
    Trends Biochem Sci 35:161-8. 2010
    ..In this review, we will summarize these recent results and offer explanations, hypotheses, and models to reconcile some of these observations...
  13. pmc Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization
    J A Diehl
    Howard Hughes Medical Institute, St Jude Children s Research Hospital, Memphis, Tennessee 38105 USA
    Genes Dev 12:3499-511. 1998
    ..Therefore, phosphorylation and proteolytic turnover of cyclin D1 and its subcellular localization during the cell division cycle are linked through the action of GSK-3beta...
  14. ncbi Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways
    C Rommel
    Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707, USA
    Nat Cell Biol 3:1009-13. 2001
    ..mammalian target of rapamycin (mTOR) and the pathway activated by phosphorylating and thereby inhibiting glycogen synthase kinase 3 (GSK3)...
  15. pmc Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3
    Michael Martin
    Department of Oral Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294 2170, USA
    Nat Immunol 6:777-84. 2005
    ..Here we report that glycogen synthase kinase 3 (GSK3) differentially regulates TLR-mediated production of pro- and anti-inflammatory cytokines...
  16. ncbi Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells
    V Stambolic
    Ontario Cancer Institute, Toronto, Canada
    Curr Biol 6:1664-8. 1996
    ..In higher eukaryotes, GSK-3 has been implicated in signal transduction pathways downstream of phosphoinositide 3-kinase and mitogen-activated protein kinases...
  17. pmc A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation
    Xin Zeng
    Neurobiology Program, Children s Hospital Boston, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 438:873-7. 2005
    ..b>Glycogen synthase kinase 3 (GSK3), which is known for its inhibitory role in Wnt signalling through the promotion of beta-catenin ..
  18. pmc Opposing effects of Tcf3 and Tcf1 control Wnt stimulation of embryonic stem cell self-renewal
    Fei Yi
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 900 S Ashland Avenue, MBRB 2270, M C 669, Chicago, Illinois 60607, USA
    Nat Cell Biol 13:762-70. 2011
    ..This work elucidates the molecular link between the effects of Wnt and the regulation of the Oct4/Sox2/Nanog network...
  19. ncbi Functional redundancy of GSK-3alpha and GSK-3beta in Wnt/beta-catenin signaling shown by using an allelic series of embryonic stem cell lines
    Bradley W Doble
    Samuel Lunenfeld Research Institute, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
    Dev Cell 12:957-71. 2007
    ..The rheostatic regulation of GSK-3 highlights the importance of considering the contributions of both homologs when studying GSK-3 functions in mammalian systems...
  20. ncbi GSK-3alpha regulates production of Alzheimer's disease amyloid-beta peptides
    Christopher J Phiel
    Department of Medicine, Division of Hematology Oncology and Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Philadelphia 19104 6148, USA
    Nature 423:435-9. 2003
    ....
  21. ncbi Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression
    Jiyong Liang
    Molecular and Cell Biology, Sunnybrook and Women s Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
    Cell Cycle 2:339-45. 2003
    ..The PI3K pathway may also play a key role in the G2/M transition and its constitutive activation may lead to defects in DNA damage checkpoint control...
  22. ncbi Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia
    Effat S Emamian
    The Rockefeller University, Laboratory of Human Neurogenetics, 1230 York Avenue, Box 313, New York, New York 10021, USA
    Nat Genet 36:131-7. 2004
    ....
  23. pmc Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin
    S Ikeda
    Department of Biochemistry, Hiroshima University School of Medicine, 1 2 3, Kasumi, Minami Ku, Hiroshima 734 8551, Japan
    EMBO J 17:1371-84. 1998
    ..These results suggest that rAxin negatively regulates the Wnt signaling pathway by interacting with GSK-3beta and beta-catenin and mediating the signal from GSK-3beta to beta-catenin...
  24. ncbi The neuron-specific isoform of glycogen synthase kinase-3beta is required for axon growth
    Zafira Castaño
    Center for Cooperative Research in Biosciences, CIC bioGUNE, Derio, Spain
    J Neurochem 113:117-30. 2010
    ..Our results suggest that GSK-3 inhibitors that target the Axin-binding site in GSK-3 will preserve the beneficial effects of GSK-3beta2 on axon growth...
  25. pmc The GSK3 hypothesis of Alzheimer's disease
    Claudie Hooper
    King s College London, MRC Centre for Neurodegenerative Research, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, UK
    J Neurochem 104:1433-9. 2008
    b>Glycogen synthase kinase 3 (GSK3) is a constitutively active, proline-directed serine/threonine kinase that plays a part in a number of physiological processes ranging from glycogen metabolism to gene transcription...
  26. pmc Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A
    X Fang
    Department of Molecular Therapeutics, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 97:11960-5. 2000
    b>Glycogen synthase kinase 3 (GSK-3) is implicated in multiple biological processes including metabolism, gene expression, cell fate determination, proliferation, and survival...
  27. ncbi Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta
    J Behrens
    Max Delbruck Center for Molecular Medicine, Robert Rossle Strasse 10, 13122 Berlin, Germany
    Science 280:596-9. 1998
    ..Thus, conductin is a component of the multiprotein complex that directs beta-catenin to degradation and is located downstream of APC. In Xenopus embryos, conductin interfered with wnt-induced axis formation...
  28. ncbi Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription
    M P Coghlan
    Department of Vascular Biology, SmithKline Beecham Pharmaceuticals, Essex, UK
    Chem Biol 7:793-803. 2000
    ..This report describes the identification and characterisation of potent and selective small molecule inhibitors of GSK-3...
  29. pmc The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation
    Markus Welcker
    Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Proc Natl Acad Sci U S A 101:9085-90. 2004
    ..Phosphorylation of c-Myc on threonine-58 (T58) by glycogen synthase kinase 3 regulates the binding of Fbw7 to c-Myc as well as Fbw7-mediated c-Myc degradation and ubiquitination...
  30. ncbi Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition
    Binhua P Zhou
    Department of Molecular and Cellular Oncology, Breast Cancer Basic Research Program, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Nat Cell Biol 6:931-40. 2004
    ..Furthermore, inhibition of GSK-3beta results in the upregulation of Snail and downregulation of E-cadherin in vivo. Thus, Snail and GSK-3beta together function as a molecular switch for many signalling pathways that lead to EMT...
  31. ncbi Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation
    Josipa Bilic
    Division of Molecular Embryology, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany
    Science 316:1619-22. 2007
    ..We propose that Wnts induce coclustering of receptors and Dvl in LRP6-signalosomes, which in turn triggers LRP6 phosphorylation to promote Axin recruitment and beta-catenin stabilization...
  32. pmc Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice
    J J Lucas
    Centro de Biologia Molecular Severo Ochoa, CSIC Universidad Autonoma de Madrid, Departamento de Morfologia, Facultad de Medicina, Universidad Autonoma de Madrid, 28049 Madrid, Spain
    EMBO J 20:27-39. 2001
    ....
  33. pmc Multiple Ras-dependent phosphorylation pathways regulate Myc protein stability
    R Sears
    Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    Genes Dev 14:2501-14. 2000
    ..These observations thus define a synergistic role for multiple Ras-mediated phosphorylation pathways in the control of Myc protein accumulation during the initial stage of cell proliferation...
  34. pmc Role that phosphorylation of GSK3 plays in insulin and Wnt signalling defined by knockin analysis
    Edward J McManus
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dundee, Scotland
    EMBO J 24:1571-83. 2005
    ..These results establish the function of Ser21/Ser9 phosphorylation in several processes in which GSK3 inactivation has previously been implicated...
  35. pmc Degradation of Mcl-1 by beta-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization
    Qingqing Ding
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
    Mol Cell Biol 27:4006-17. 2007
    ..Here, we report that glycogen synthase kinase 3 (GSK-3) was required for Mcl-1 degradation, and we identified a novel mechanism for proteasome-mediated ..
  36. ncbi Involvement of GSK-3 in regulation of murine embryonic stem cell self-renewal revealed by a series of bisindolylmaleimides
    Heather K Bone
    Department of Pharmacy and Pharmacology, Centre for Regenerative Medicine, University of Bath, Bath, UK
    Chem Biol 16:15-27. 2009
    ..The mechanisms controlling ESC self-renewal are under intense investigation, and glycogen synthase kinase 3 (GSK-3) has been implicated in regulating both self-renewal and differentiation...
  37. pmc Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo
    Wendy Noble
    Center for Dementia Research, Nathan S Kline Institute, New York University, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
    Proc Natl Acad Sci U S A 102:6990-5. 2005
    ..These results support the idea that kinases are involved in tauopathy progression and that kinase inhibitors may be effective therapeutically...
  38. ncbi Cellular survival: a play in three Akts
    S R Datta
    Division of Neuroscience, Children s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115 USA
    Genes Dev 13:2905-27. 1999
  39. ncbi Both the establishment and the maintenance of neuronal polarity require active mechanisms: critical roles of GSK-3beta and its upstream regulators
    Hui Jiang
    Institute of Neuroscience, Shanghai Institutes of Biological Sciences, The Graduate School, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China
    Cell 120:123-35. 2005
    ....
  40. pmc β-catenin enhances Oct-4 activity and reinforces pluripotency through a TCF-independent mechanism
    Kevin F Kelly
    Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario, Canada
    Cell Stem Cell 8:214-27. 2011
    ..Collectively, our data suggest previously underappreciated, divergent TCF-dependent and TCF-independent roles for β-catenin in ESCs...
  41. ncbi The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3
    C Yost
    Department of Biochemistry, University of Washington School of Medicine, Seattle, 98195 7370, USA
    Genes Dev 10:1443-54. 1996
    ..These studies provide a basis for understanding the interaction between Xgsk-3 and beta-catenin in the establishment of the dorsal-ventral axis in early Xenopus embryos...
  42. pmc Glycogen synthase kinase-3 (GSK3): inflammation, diseases, and therapeutics
    Richard S Jope
    Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Sparks Center 1057, 1720 Seventh Avenue South, Birmingham, AL 35294 0017, USA
    Neurochem Res 32:577-95. 2007
    ..Thus, GSK3 may contribute not only to primary pathologies in these diseases, but also to the associated inflammation, suggesting that GSK3 inhibitors may have multiple effects influencing these conditions...
  43. pmc Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes
    Vincent F Taelman
    Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095 1662, USA
    Cell 143:1136-48. 2010
    Canonical Wnt signaling requires inhibition of Glycogen Synthase Kinase 3 (GSK3) activity, but the molecular mechanism by which this is achieved remains unclear...
  44. ncbi Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation
    K P Hoeflich
    Ontario Cancer Institute Princess Margaret Hospital, Toronto, Canada
    Nature 406:86-90. 2000
    ..Thus, GSK-3beta facilitates NF-kappaB function...
  45. pmc Glycogen synthase kinase 3 phosphorylates kinesin light chains and negatively regulates kinesin-based motility
    Gerardo Morfini
    Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9039, USA
    EMBO J 21:281-93. 2002
    ..and in vivo evidence that kinesin light chains (KLCs) interact with and are in vivo substrates for glycogen synthase kinase 3 (GSK3)...
  46. pmc Phosphoinositide 3-kinase and Akt are essential for Sonic Hedgehog signaling
    Natalia A Riobo
    Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, 1157 BRBII III, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 103:4505-10. 2006
    ..Our findings provide a basis for the synergistic role of PI3-kinase/Akt in Hh signaling in embryonic development and Hh-dependent tumors...
  47. ncbi LTP inhibits LTD in the hippocampus via regulation of GSK3beta
    Stephane Peineau
    MRC Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University Walk, Bristol, BS8 1TD, United Kingdom
    Neuron 53:703-17. 2007
    ..We conclude that the regulation of GSK3beta activity provides a powerful mechanism to preserve information encoded during LTP from erasure by subsequent LTD, perhaps thereby permitting the initial consolidation of learnt information...
  48. pmc Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation
    Lilia Topol
    Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 162:899-908. 2003
    ..Furthermore, we provide evidence that Wnt-5a also acts in vivo to promote beta-catenin degradation in regulating mammalian limb development and possibly in suppressing tumor formation...
  49. pmc Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3beta/beta-catenin signaling
    Yingwei Mao
    Howard Hughes Medical Institute, Cambridge, MA 02139, USA
    Cell 136:1017-31. 2009
    ..Together, these results implicate DISC1 in GSK3beta/beta-catenin signaling pathways and provide a framework for understanding how alterations in this pathway may contribute to the etiology of psychiatric disorders...
  50. pmc Glycogen synthase kinase 3 inhibition promotes lysosomal biogenesis and autophagic degradation of the amyloid-β precursor protein
    Callum Parr
    Division of Brain Sciences, Imperial College London, London, United Kingdom
    Mol Cell Biol 32:4410-8. 2012
    Alzheimer's disease (AD) has been associated with altered activity of glycogen synthase kinase 3 (GSK3) isozymes, which are proposed to contribute to both neurofibrillary tangles and amyloid plaque formation...
  51. pmc GSK3 signalling in neural development
    Eun Mi Hur
    Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    Nat Rev Neurosci 11:539-51. 2010
    Recent evidence suggests that glycogen synthase kinase 3 (GSK3) proteins and their upstream and downstream regulators have key roles in many fundamental processes during neurodevelopment...
  52. pmc Dynamin I phosphorylation by GSK3 controls activity-dependent bulk endocytosis of synaptic vesicles
    Emma L Clayton
    Centre for Integrative Physiology, George Square, University of Edinburgh, Edinburgh, Scotland, UK
    Nat Neurosci 13:845-51. 2010
    b>Glycogen synthase kinase 3 (GSK3) is a critical enzyme in neuronal physiology; however, it is not yet known whether it has any specific role in presynaptic function...
  53. ncbi GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity
    Takeshi Yoshimura
    Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa Ku, Nagoya, Aichi 466 8550, Japan
    Cell 120:137-49. 2005
    ..Knockdown of CRMP-2 inhibited NT-3-induced axon outgrowth. These results suggest that NT-3 decreases phosphorylated CRMP-2 and increases nonphosphorylated active CRMP-2, thereby promoting axon outgrowth...
  54. pmc Phosphorylation of Tip60 by GSK-3 determines the induction of PUMA and apoptosis by p53
    Celine Charvet
    Institute of Molecular Medicine and Cell Research, Albert Ludwigs University Freiburg, Stefan Meier Strasse 17, 79104 Freiburg, Germany
    Mol Cell 42:584-96. 2011
    ..Our data suggest that GSK-3 mediated Tip60S86 phosphorylation provides a link between PI3K signaling and the choice for or against apoptosis induction by p53...
  55. pmc Phosphorylation by p38 MAPK as an alternative pathway for GSK3beta inactivation
    Tina M Thornton
    Department of Medicine Immunobiology Program, University of Vermont, Burlington, VT 05405 0068, USA
    Science 320:667-70. 2008
    ..Activation of beta-catenin-mediated signaling through GSK3beta inhibition provides a potential mechanism for p38 MAPK-mediated survival in specific tissues...
  56. pmc Prion peptide induces neuronal cell death through a pathway involving glycogen synthase kinase 3
    Mar Perez
    Centro de Biologia Molecular Severo Ochoa CSIC UAM, Universidad Autonoma Madrid, 28049 Madrid, Spain
    Biochem J 372:129-36. 2003
    ..study, we show that the addition of this prion peptide to cultured neurons increases the activity of glycogen synthase kinase 3 (GSK-3), which is accompanied by the enhanced phosphorylation of some microtubule-associated proteins ..
  57. pmc Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal
    Luis C Fuentealba
    Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Los Angeles, CA 90095 1662, USA
    Cell 131:980-93. 2007
    ..Epistatic experiments suggested that the dorsoventral (BMP) and anteroposterior (Wnt/GSK3) patterning gradients are integrated at the level of Smad1 phosphorylations during embryonic pattern formation...
  58. ncbi Glycogen synthase kinase 3beta (GSK3beta) in tumorigenesis and cancer chemotherapy
    Jia Luo
    Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Robert C Byrd Health Sciences Center, Morgantown, WV 26506, USA
    Cancer Lett 273:194-200. 2009
    ..This mini-review discusses the role of GSK3beta in tumorigenesis/cancer progression as well as its modulation of cancer chemotherapy...
  59. pmc Regulation and localization of tyrosine216 phosphorylation of glycogen synthase kinase-3beta in cellular and animal models of neuronal degeneration
    R V Bhat
    Neuroscience Department, AstraZeneca Pharmaceuticals, 1800 Concord Pike, Wilmington, DE 19850 5437, USA
    Proc Natl Acad Sci U S A 97:11074-9. 2000
    ..Taken together, these results suggest that Y(216) phosphorylation of GSK3beta represents an important mechanism by which cellular insults can lead to neuronal death...
  60. pmc Brassinosteroid signal transduction from cell-surface receptor kinases to nuclear transcription factors
    Tae Wuk Kim
    Department of Plant Biology, Carnegie Institution for Science, Stanford, CA 94305, USA
    Nat Cell Biol 11:1254-60. 2009
    ..This study establishes a fully connected BR signalling pathway and provides new insights into the mechanism of GSK3 regulation...
  61. ncbi GSK-3-selective inhibitors derived from Tyrian purple indirubins
    Laurent Meijer
    CNRS, Cell Cycle Group, Station Biologique, BP 74, 29682 Roscoff Cedex, Bretagne, France
    Chem Biol 10:1255-66. 2003
    ..BIO but not 1-methyl-BIO closely mimicked Wnt signaling in Xenopus embryos. 6-bromoindirubins thus provide a new scaffold for the development of selective and potent pharmacological inhibitors of GSK-3...
  62. pmc Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore
    Magdalena Juhaszova
    Laboratory of Cardiovascular Science, Gerontology Research Center, Intramural Research Program, National Institute on Aging, NIH, Baltimore, Maryland 21224 6825, USA
    J Clin Invest 113:1535-49. 2004
    ..The convergence of these pathways via inhibition of GSK-3beta on the end effector, the permeability transition pore complex, to limit MPT induction is the general mechanism of cardiomyocyte protection...
  63. ncbi A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells
    Jong In Yook
    Department of Oral Pathology, Oral Cancer Research Institute, College of Dentistry Yonsei University, Seoul 120 752, Korea
    Nat Cell Biol 8:1398-406. 2006
    ..As dysregulated Wnt signalling marks a diverse array of cancerous tissue types, the identification of a beta-catenin-TCF-regulated Axin2-GSK3beta-Snail1 axis provides new mechanistic insights into cancer-associated EMT programmes...
  64. pmc Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase
    M Delcommenne
    British Columbia Cancer Agency, Jack Bell Research Centre, 2660 Oak Street, Vancouver, British Columbia V6H 3Z6 Canada
    Proc Natl Acad Sci U S A 95:11211-6. 1998
    ..ILK is an upstream effector of the Pi(3)K-dependent regulation of both protein kinase B (PKB/AKT) and glycogen synthase kinase 3 (GSK-3)...
  65. ncbi PAR-1 kinase plays an initiator role in a temporally ordered phosphorylation process that confers tau toxicity in Drosophila
    Isao Nishimura
    Laboratory of Developmental Neurobiology, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Cell 116:671-82. 2004
    ..This phosphorylation event is a prerequisite for the action of downstream kinases, including glycogen synthase kinase 3 (GSK-3) and cyclin-dependent kinase-5 (Cdk5), to phosphorylate several other sites and generate disease-..
  66. ncbi Glycogen synthase kinase-3beta haploinsufficiency mimics the behavioral and molecular effects of lithium
    W Timothy O'Brien
    Division of Hematology Oncology, Department of Medicine, and Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6148, USA
    J Neurosci 24:6791-8. 2004
    ..These observations support a central role for GSK-3beta in mediating behavioral responses to lithium...
  67. pmc Glycogen synthase kinase 3: more than a namesake
    Geetha Vani Rayasam
    Department of Pharmacology, Research and Development R and D III, Ranbaxy Research Labs, Gurgaon, Haryana, India
    Br J Pharmacol 156:885-98. 2009
    b>Glycogen synthase kinase 3 (GSK3), a constitutively acting multi-functional serine threonine kinase is involved in diverse physiological pathways ranging from metabolism, cell cycle, gene expression, development and oncogenesis to ..
  68. pmc Further evidence that the tyrosine phosphorylation of glycogen synthase kinase-3 (GSK3) in mammalian cells is an autophosphorylation event
    Adam Cole
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 377:249-55. 2004
    ..Our results indicate that the tyrosine phosphorylation of GSK3 is an intramolecular autophosphorylation event in the cells that we have studied and that this modification enhances the stability of the enzyme...
  69. ncbi Regulation of Wnt signaling during adipogenesis
    Christina N Bennett
    Department of Physiology, 7620 Medical Science II, University of Michigan Medical School, 1301 E Catherine Street, Ann Arbor, MI 48109 0622, USA
    J Biol Chem 277:30998-1004. 2002
    ..Here, we demonstrate that a specific inhibitor of glycogen synthase kinase 3, CHIR 99021, mimics Wnt signaling in preadipocytes...
  70. ncbi Phosphorylation of serine 468 by GSK-3beta negatively regulates basal p65 NF-kappaB activity
    Holger Buss
    Institute of Pharmacology, Medical School Hannover, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    J Biol Chem 279:49571-4. 2004
    ..Collectively our results suggest that a GSK-3beta-PP1-dependent mechanism regulates phosphorylation of p65 NF-kappaB at Ser(468) in unstimulated cells and thereby controls the basal activity of NF-kappaB...
  71. ncbi Formation of the head organizer in hydra involves the canonical Wnt pathway
    Mariya Broun
    Department of Developmental and Cell Biology and the Developmental Biology Center, University of California, Irvine, CA 92697, USA
    Development 132:2907-16. 2005
    ..Hence, the role of the canonical Wnt pathway for the initiation of axis formation was established early in metazoan evolution...
  72. pmc Differential roles of GSK-3β during myocardial ischemia and ischemia/reperfusion
    Peiyong Zhai
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ New Jersey Medical School, Newark, NJ 07103, USA
    Circ Res 109:502-11. 2011
    ..Inhibition of glycogen synthase kinase-3 (GSK-3) protects the heart during ischemia/reperfusion (I/R), yet the underlying mechanisms of cardioprotection afforded by beta isoform-specific inhibition GSK-3 remain to be elucidated...
  73. ncbi Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of beta-catenin, and enhanced tumor cell invasion
    Zhimin Lu
    Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Cancer Cell 4:499-515. 2003
    ..We propose that EGF-induced negative regulation of caveolin-1 plays a central role in the complex cellular changes leading to metastasis...
  74. ncbi Inhibition of GSK3beta enhances both adhesive and signalling activities of beta-catenin in mouse embryonic stem cells
    Galina S Sineva
    Institute of Cytology, Russian Academy of Sciences, St Petersburg, Russia
    Biol Cell 102:549-60. 2010
    ..In some cases, inhibition of GSK3beta activity was shown to promote self-renewal of ESCs (embryonic stem cells), but immediate effects of GSK3beta inhibitors in these cells still remain elusive...
  75. pmc Deficiency in the inhibitory serine-phosphorylation of glycogen synthase kinase-3 increases sensitivity to mood disturbances
    Abigail Polter
    Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294 0017, USA
    Neuropsychopharmacology 35:1761-74. 2010
    ....
  76. ncbi Diabetes mellitus abrogates erythropoietin-induced cardioprotection against ischemic-reperfusion injury by alteration of the RISK/GSK-3β signaling
    Nehmat Ghaboura
    Protection et remodelage du myocarde, UPRES EA 3860, Faculte de Medecine, Universite d Angers, Rue Haute de Reculee, 49045 Angers Cedex 1, France
    Basic Res Cardiol 106:147-62. 2011
    ..In conclusion, direct inhibition of GSK-3β may provide an alternative strategy to protect diabetic hearts against I/R injury...
  77. ncbi Abeta exacerbates the neuronal dysfunction caused by human tau expression in a Drosophila model of Alzheimer's disease
    James Folwell
    Department of Neurosciences, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK
    Exp Neurol 223:401-9. 2010
    ..It is therefore possible to speculate that the mechanism by which Abeta(42) interacts with tau in the pathogenesis of AD is by down-regulating endogenous wnt signalling...
  78. ncbi Selective small-molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurones from death
    D A Cross
    Neurology Centre of Excellence in Drug Discovery, GlaxoSmithKline Pharmaceuticals, Harlow, Essex, UK
    J Neurochem 77:94-102. 2001
    ....
  79. ncbi The ground state of pluripotency
    Jason Wray
    Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK
    Biochem Soc Trans 38:1027-32. 2010
    ..Inhibition of GSK3 (glycogen synthase kinase 3) reinforces this effect...
  80. ncbi GSK-3 is a master regulator of neural progenitor homeostasis
    Woo Yang Kim
    Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
    Nat Neurosci 12:1390-7. 2009
    ..It has been suggested that glycogen synthase kinase 3 (GSK-3) acts as an integrating molecule for multiple proliferation and differentiation signals because ..
  81. pmc The role of GSK-3 in synaptic plasticity
    S Peineau
    Department of Anatomy, MRC Centre for Synaptic Plasticity, School of Medical Sciences, University Walk, Bristol, UK
    Br J Pharmacol 153:S428-37. 2008
    ..The present article summarizes this recent work and discusses its potential relevance to the treatment of neurological disorders...
  82. ncbi GSK3 inhibitors: development and therapeutic potential
    Philip Cohen
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK
    Nat Rev Drug Discov 3:479-87. 2004
  83. pmc GSK3 takes centre stage more than 20 years after its discovery
    S Frame
    Division of Signal Transduction Therapy, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 359:1-16. 2001
    ..These latest findings have generated an enormous amount of interest in the development of drugs that inhibit GSK3 and which may have therapeutic potential for the treatment of diabetes, stroke and Alzheimer's disease...
  84. ncbi Glycogen synthase kinase-3 inhibition is integral to long-term potentiation
    Claudie Hooper
    MRC Centre for Neurodegeneration Research, Centre for the Cellular Basis of Behaviour, Institute of Psychiatry, King s College London, De Crespigny Park, London SE5 8AF, UK
    Eur J Neurosci 25:81-6. 2007
    ..It follows that this role of GSK-3beta in LTP might underlie some of the cognitive dysfunction in diseases where GSK-3 dysfunction has been implicated, including Alzheimer's and other dementias...
  85. ncbi Increased level of active GSK-3beta in Alzheimer's disease and accumulation in argyrophilic grains and in neurones at different stages of neurofibrillary degeneration
    K Leroy
    Laboratory of Histology, Neuroanatomy and Neuropathology, Universite Libre de Bruxelles, Campus Erasme, 808 Route de Lennik, B 1070 Brussels, Belgium
    Neuropathol Appl Neurobiol 33:43-55. 2007
    ....
  86. ncbi Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling
    A C Hall
    Developmental Biology Research Centre, The Randall Institute, King s College London, United Kingdom
    Cell 100:525-35. 2000
    ..Wnt-7a mutant mice show a delay in the morphological maturation of glomerular rosettes and in the accumulation of synapsin I. We propose that WNT-7a can function as a synaptogenic factor...
  87. pmc Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation
    Olivia A Shipton
    Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom
    J Neurosci 31:1688-92. 2011
    ..Moreover, we show that Aβ increases tau phosphorylation and that a specific inhibitor of the tau kinase glycogen synthase kinase 3 blocks the increased tau phosphorylation induced by Aβ and prevents Aβ-induced impairment of LTP in ..
  88. ncbi Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation
    Markus Welcker
    Divisions of Clinical Research and Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Mol Cell 12:381-92. 2003
    ..Thus, cyclin E turnover is controlled by multiple biological inputs and cannot be understood in terms of autophosphorylation alone...
  89. ncbi IFN-gamma suppresses IL-10 production and synergizes with TLR2 by regulating GSK3 and CREB/AP-1 proteins
    Xiaoyu Hu
    Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, Weill Graduate School of Medical Sciences of Cornell University, New York, New York 10021, USA
    Immunity 24:563-74. 2006
    ..GSK3 and CREB/AP-1 are key players in integrating IFN-gamma and TLR2 responses in innate immunity and inflammation...
  90. ncbi GSK3B polymorphisms alter transcription and splicing in Parkinson's disease
    John B J Kwok
    Garvan Institute of Medical Research, University of New South Wales, Barker Street, Randwick, Sydney NSW 2031, Australia
    Ann Neurol 58:829-39. 2005
    ..64; p = 0.007; (H1/H1 individuals: odds ratio, 0.68; p < 0.001). Ours results suggest GSK3B polymorphisms alter transcription and splicing and interact with Tau haplotypes to modify disease risk in PD...
  91. pmc Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy
    Zhong Wang
    Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA
    Nature 455:1205-9. 2008
    b>Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine kinase that participates in numerous signalling pathways involved in diverse physiological processes...
  92. ncbi Aβ(1-42) inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK-3β
    Jihoon Jo
    Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK
    Nat Neurosci 14:545-7. 2011
    ..We found that a signaling pathway involving caspase-3, Akt1 and glycogen synthase kinase-3β is an important mediator of this effect in rats and mice...
  93. ncbi Myeloid cell leukemia-1 inversely correlates with glycogen synthase kinase-3beta activity and associates with poor prognosis in human breast cancer
    Qingqing Ding
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 67:4564-71. 2007
    ..Our results indicate that Mcl-1 stabilization by GSK-3beta inactivation could be involved in tumorigenesis and serve as a useful prognostic marker for human breast cancer...
  94. ncbi Valproate protects cells from ER stress-induced lipid accumulation and apoptosis by inhibiting glycogen synthase kinase-3
    Anna J Kim
    Department of Biochemistry, McMaster University, Hamilton, Ontario, L8S 4LB, Canada
    J Cell Sci 118:89-99. 2005
    ..Strategies to protect cells from agents/conditions that induce ER stress may have potential in the treatment of the growing number of diseases and disorders linked to ER dysfunction...
  95. ncbi Role of glycogen synthase kinase-3 in TNF-alpha-induced NF-kappaB activation and apoptosis in hepatocytes
    Robert F Schwabe
    Department of Medicine, Biochemistry, and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Am J Physiol Gastrointest Liver Physiol 283:G204-11. 2002
    ..These results indicate that GSK-3 protects hepatocytes from TNF-alpha-induced apoptosis through p65 phosphorylation and upregulation of NF-kappaB transactivation...
  96. pmc GSK3beta phosphorylation modulates CLASP-microtubule association and lamella microtubule attachment
    Praveen Kumar
    Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA 94143, USA
    J Cell Biol 184:895-908. 2009
    ..This indicates that CLASP-mediated stabilization of peripheral MTs, which likely occurs in the vicinity of focal adhesions, may be regulated by local GSK3beta inactivation...
  97. ncbi Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition
    R Dajani
    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, United Kingdom
    Cell 105:721-32. 2001
    b>Glycogen synthase kinase 3 beta (GSK3 beta) plays a key role in insulin and Wnt signaling, phosphorylating downstream targets by default, and becoming inhibited following the extracellular signaling event...
  98. pmc Role of glycogen synthase kinase-3beta in cardioprotection
    Magdalena Juhaszova
    Laboratory of Cardiovascular Science, Gerontology Research Center, Box 13, National Institute on Aging, NIH, Baltimore, Maryland 21224 6825, USA
    Circ Res 104:1240-52. 2009
    ....
  99. pmc Mania-like behavior induced by disruption of CLOCK
    Kole Roybal
    Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390 9070, USA
    Proc Natl Acad Sci U S A 104:6406-11. 2007
    ..These findings establish the Clock mutant mice as a previously unrecognized model of human mania and reveal an important role for CLOCK in the dopaminergic system in regulating behavior and mood...
  100. ncbi APC and GSK-3beta are involved in mPar3 targeting to the nascent axon and establishment of neuronal polarity
    Song Hai Shi
    Departments of Physiology and Biochemistry, Howard Hughes Medical Institute, University of California at San Francisco, 1550 4th Street, San Francisco, CA 94143 0725, USA
    Curr Biol 14:2025-32. 2004
    ....
  101. ncbi Glycogen synthase kinase 3alpha-specific regulation of murine hepatic glycogen metabolism
    Katrina MacAulay
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada
    Cell Metab 6:329-37. 2007
    b>Glycogen synthase kinase 3 comprises two isoforms (GSK-3alpha and GSK-3beta) that are implicated in type II diabetes, neurodegeneration, and cancer...

Research Grants69

  1. Regulation of myocardial growth and death by GSK-3
    Junichi Sadoshima; Fiscal Year: 2013
    ..The knowledge obtained from this investigation should be useful for the development of better treatment for heart failure, ischemic injury and stem cell therapy. ..
  2. Molecular Regulation of Progesterone Synthesis
    John S Davis; Fiscal Year: 2013
    ..overall hypothesis that activation of protein kinase A inhibits the intracellular signaling intermediate glycogen synthase kinase 3 (GSK3), which contributes to the steroidogenic response to LH by increasing the availability of a 2-..
  3. New insights in mechanisms of renal injury
    Balakuntalam S Kasinath; Fiscal Year: 2013
    ..Upstream regulators and downstream effectors of GSK 3beta in transcription and translation pathways involved in matrix protein synthesis will be explored in renal tissues as stated in Aim 1. ..
  4. Extracellular ubiquitin: role in myocyte apoptosis and myocardial remodeling
    Krishna Singh; Fiscal Year: 2010
    ....
  5. Cell stress, development, and stimulant-induced behavior: Regulation by GSK3
    Marjelo A Mines; Fiscal Year: 2012
    ..Among these are understanding biochemical mechanisms that impair cellular functions, mechanisms controlling vulnerability, and behavioral outcomes of interventions, each of which is addressed by the three Specific Aims of this project. ..
  6. Regulation of apoptosis by PI 3-kinase/Akt signaling
    Geoffrey M Cooper; Fiscal Year: 2012
    ..The present proposal seeks to further understand the mechanism by which this pathway regulates cell survival. Discoveries of novel targets of PI 3-kinase signaling may provide new targets for cancer treatment. ..
  7. Mechanisms of Airway Smooth Muscle Hypertrophy
    Marc B Hershenson; Fiscal Year: 2013
    ..Completion of this work will provide insight into the pathogenesis of BPD, lead to the development of more accurate biomarkers, and provide new information on the role of matricellular proteins in lung fibrosis. ..
  8. Interactions Between Depression, Neuroinflammation and Glycogen Synthase Kinase-3
    Eleonore Beurel; Fiscal Year: 2011
    ..The goals are to clarify potential causative mechanisms and discern how these are altered by therapeutic interventions with the aim of developing better therapeutic interventions for mood disorders. ..
  9. Cannabinoid regulation of glycogen synthase kinase-3
    Cecilia J Hillard; Fiscal Year: 2013
    ..b>Glycogen synthase kinase 3 (GSK-3) is emerging as an important regulatory kinase in the limbic brain;over-activity of GSK-3 has ..
  10. GSK3beta, a mediator of ethanol neurotoxicity
    Xianglin Shi; Fiscal Year: 2013
    ..The loss of CNS neurons may underlie many of the behavioral deficits observed in FASD. Glycogen synthase kinase 3[unreadable] (GSK3[unreadable]), a serine/threonine kinase, is an important mediator of neuron ..
  11. SECRETION AND BIOSYNTHESIS OF INSULIN
    Michael L McDaniel; Fiscal Year: 2012
    ....
  12. GSK3: immunoregulator in experimental autoimmune encephalomyelitis (EAE)
    Patrizia De Sarno; Fiscal Year: 2012
    ....
  13. Interactions Between Depression, Neuroinflammation and Glycogen Synthase Kinase-3
    Eleonore Beurel; Fiscal Year: 2013
    ..Specific Aim 3 will test the hypothesis that GSK3 promotes depression-like behavioral responses to inflammatory and environmental stress. ..
  14. Targeting stress-mediated pathways in the treatment of muscle insulin resistance
    Paige C Geiger; Fiscal Year: 2013
    ....
  15. Mechanisms of Fatty-Acid Inhibition of the Insulin Gene
    Vincent Poitout; Fiscal Year: 2013
    ..We anticipate that these findings will serve as a basis to design novel therapeutic approaches to prevent the deterioration of [unreadable]-cell function in T2D. ..
  16. BRCA1 and progesterone receptors in breast cancer
    Eva Y Lee; Fiscal Year: 2013
    ..How the progesterone receptor activity is regulated will be studied. The results will provide insights into breast cancer intervention and will have important implications for in breast cancer prevention and treatment. ..
  17. ROLE OF WNT SIGNALING IN CHRONIC ALCOHOLIC LIVER DISEASE
    Miran Kim; Fiscal Year: 2013
    ..e., insulin/IGF and Wnt. Moreover, the results from these investigations could identify novel therapeutic targets for treating chronic ALD, including restoration of liver function following bouts of injury. ..
  18. The Role of HIF-1 in Neurogenic and Behavior Responses to Antidepressants.
    W TIMOTHY O'BRIEN; Fiscal Year: 2013
    ..A new connection between hypoxia signaling and the actions antidepressants could lead to a better understanding of and new approaches to the treatment of affective disorders. ..
  19. Fundamental mechanisms of protein kinase activation loop autophosphorlyation
    Vaughn Cleghon; Fiscal Year: 2013
    ..DYRKs and glycogen synthase kinase 3 (GSK3) enzymes are dual-specificity kinases that autophosphorylate their activation loop on an essential ..
  20. Interstitial Cells of Cajal in Diabetic Gastropathy
    TAMAS ORDOG; Fiscal Year: 2013
    ..Our second specific aim is to determine the role and molecular mechanisms-of-action of glycogen synthase kinase 3 (Gsk3) as an extrinsic factor in regulating ICC-SC through stem cell factor expression in smooth muscle ..
  21. Microtubule dynamics during cell polarity and migration
    Torsten Wittmann; Fiscal Year: 2012
    ..This association of CLASPs along lamella microtubules is decreased through phosphorylation by glycogen synthase kinase 3? (GSK3?), an emerging integrator of cell polarity pathways...
  22. Functional Characterization of CCDC130 Gene
    Deepak Kumar; Fiscal Year: 2012
    ..The proposal may lead to development of a novel cancer biomarker and/or a drug target. The proposal will catalyze PIs transition to non-SCORE funding mechanism and enhance biomedical research at a minority serving institution like UDC. ..
  23. REGULATION OF PROTEIN TURNOVER IN SEPSIS
    Scot R Kimball; Fiscal Year: 2010
    ....
  24. Control of NF-kappaB Activity
    ALBERT SIDNEY BALDWIN; Fiscal Year: 2013
    ..abstract_text> ..
  25. Signaling pathways regulated by GSK3 in hematopoietic stem cell
    Jian Huang; Fiscal Year: 2012
    ..The long-term goals of this project are to extend our understanding of HSC biology and to improve HSC/bone marrow transplantation. ) ..
  26. Suicide Endophenotypes and Molecular Mechanisms of Lithium Action
    Todd D Gould; Fiscal Year: 2013
    ..This application proposes experiments in the context of endophenotype strategies that will reveal molecular mechanisms whereby lithium acts to exert its therapeutics effects. ..
  27. Mechanism of Gli3 processing in Hedgehog signaling
    Baolin Wang; Fiscal Year: 2013
    ..Gli3 processing requires C-terminal phosphorylation by protein kinase A (PKA), glycogen synthase kinase 3 (GSK3), and casein kinase 1 (CK1), and subsequent ubiquitination by SCFTrCP E3 ubiquitin ligase...
  28. Molecular mechanisms of Myotonic Dystrophy 1
    Lubov T Timchenko; Fiscal Year: 2012
    ..Searching for the mechanisms of the reduction of cyclin D3 in DM1, we found that the active glycogen synthase kinase 3? (GSK3?) is increased in DM1 muscle biopsies and in muscle of the DM1 mouse model (HSALR mice)...
  29. Regulation of Renal Response to Vasopressin by Glycogen Synthase
    Reena Rao; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Glycogen synthase kinase 3 (GSK3) is a family of serine/threonine protein kinases that consists of two isoforms, GSK3a and GSK3[unreadable]...
  30. Identifying and characterizing gene(s) involved in beta-amyloid production.
    Huaxi Xu; Fiscal Year: 2013
    ....
  31. STEROID CONTROL OF EPITHELIAL CELL-CELL INTERACTIONS
    Gary L Firestone; Fiscal Year: 2011
    ..A final goal is to functionally characterize the roles of GSK3 and CAS and their degradative systems in the steroid dependent control of beta-catenin dynamics, apical junction organization and tight junction formation. ..
  32. Regulating Hematopoietic Stem Cell Homeostasis through GSK-3
    Wei Tong; Fiscal Year: 2013
    ..These studies will define the function(s) of GSK-3 in normal hematopoiesis and may lead to the development of novel therapeutic approaches to expand HSCs in hematopoietic disorders. ..
  33. BBB Protection in HIV Infection: Barrier-shielding effects of PARP inhibition
    Yuri Persidsky; Fiscal Year: 2013
    ..PARP inhibitors have now reached the stage of clinical testing for cancer treatment, assuring quick translation to therapy of immune/inflammatory disorders. ..
  34. GSK3 regulation of suprachiasmatic neuronal excitability and light entrainment
    JODI RENEE PAUL; Fiscal Year: 2013
    ..b>Glycogen synthase kinase 3 (GSK3) is a serine-threonine kinase that is an emerging regulator of mammalian circadian rhythms and has ..
  35. Circadian dysfunction and GSK3 in neurodegenerative disease
    Karen L Gamble; Fiscal Year: 2013
    ..This project will test the hypothesis that glycogen synthase kinase 3 provides a time-of-day-specific gating mechanism for intrinsic excitability, and that disruptions i ..
  36. Discovery of Novel Antitumor Agents Effective Against Pancreatic Cancer
    Amy Wright; Fiscal Year: 2009
    ..We will also continue to screen materials against a panel of pancreatic cancer cell lines. ..
  37. A Molecular Mechanism for Lithium Action
    Peter S Klein; Fiscal Year: 2010
    ....
  38. PAR-1 Signaling and HAND
    KATHLEEN ANNE MAGUIRE-ZEISS; Fiscal Year: 2013
    ..Moreover, newly developed orally available PAR-1 antagonists that are now in clinical trials for coronary artery disease might be considered for treatment of the same. ..
  39. Effects of lithium on cellular signaling
    Richard S Jope; Fiscal Year: 2011
    ..Altogether, this project will continue to address important problems concerning the causes and treatments of mood disorders. ..
  40. Protein kinase B (Akt)-mediated pathway regulating endothelial-barrier function
    SOMANATH P RAMMOHAN SHENOY; Fiscal Year: 2013
    ..Once we identify these signaling partners and understand how Akt coordinates cytoskeletal and focal-adhesion dynamics in vitro, we will extend our findings in vivo. ..
  41. INSULIN SIGNALING DEFECTS IN PCOS
    Ricardo Azziz; Fiscal Year: 2010
    ..Moreover, we anticipate that by advancing the rate of our existing research, the supplement will enable us to lay the foundations for future submissions, which has the potential to both secure existing jobs and create new ones ..
  42. Akt/GSK-3 Signaling Cascade and the Actions of Dopamine
    Marc G Caron; Fiscal Year: 2013
    ....
  43. Effects of lithium on cellular signaling
    Richard S Jope; Fiscal Year: 2013
    ..Altogether, this project will continue to address important problems concerning the causes and treatments of mood disorders. ..
  44. MANIPULATION OF KINASE ACTIVITY BY KSHV LANA
    S Diane Hayward; Fiscal Year: 2010
    ..The LANA protein is produced by KSHV in these cancers. We are testing the hypothesis that LANA changes the activity of cell enzymes called kinases and that this sets the cell on a path that can lead to cancer. ..
  45. Stability of prolactin receptor and prolactin signaling
    Serge Y Fuchs; Fiscal Year: 2010
    ..via PRLr ubiquitination and lysosomal degradation that depends on PRLr phosphorylation on Ser349, (ii) glycogen synthase kinase 3 (GSK3) is implicated in PRLr phosphorylation on Ser349, and (iii) this Ser349 phosphorylation as well as ..
  46. Therapeutic targeting of GSK3beta: A novel approach for podocyte protection
    Rujun Gong; Fiscal Year: 2013
    ..Collectively, these studies should allow rapid progress to clinical trials of existing drugs with GSK3 inhibitory activities to improve podocyte injury, induce proteinuria remission, and slow progression of glomerulosclerosis in man. ..
  47. Signaling pathways regulated by GSK3 in hematopoietic stem cell
    Jian Huang; Fiscal Year: 2013
    ..The knowledge learned from these studies will provide new insights into the mechanisms of the regulation of HSC self-renewal and differentiation and may improve the therapy of hematopoietic disorders. 1 ..
  48. Wnt/GSK3/beta Catenin Signaling as a Target for Treatment of Bipolar Disorder
    Rakesh Karmacharya; Fiscal Year: 2013
    ....
  49. Posttranslational processing of tau: function & dysfunc.
    Gail Johnson; Fiscal Year: 2009
    ..The central hypothesis of this application is that a cascade of tau phosphorylation events in which glycogen synthase kinase 3 (GSK3) plays a key role, initially results in impaired microtubule binding and subsequently, in ..
  50. Targeting Wnt and mTOR to expand hematopoietic stem cells
    Peter S Klein; Fiscal Year: 2012
    ..The proposal explores new approaches to enhance blood formation for bone marrow transplantation and in patients with low blood counts due to disease or chemotherapy. ..
  51. GSK3-beta Signaling in Medullary Thyroid Cancer
    Herbert Chen; Fiscal Year: 2013
    ..In this proposal, we will explore the potential to utilize GSK3B inhibitors to improve surgical outcomes for patients with metastatic MTC. ..
  52. Glycogen Synthase Kinase-3 as a drug target for Trypanosoma brucei
    Wesley C Van Voorhis; Fiscal Year: 2012
    ..The available drugs for T. brucei infection are very toxic, some of them causing up to 5% mortality from the therapy alone. New drugs for this infection are clearly needed. ..
  53. Canonical Wnt Signaling by the Proteolytc Processing of LRP6
    BRANDON RICHARD BEAGLE; Fiscal Year: 2010
    ..The Wnt canonical pathway plays a major role in regulating the activity of glycogen synthase kinase 3 (GSK3)...
  54. The role of EP4 in fibronectin-induced human lung cancer cell growth
    ShouWei Han; Fiscal Year: 2010
    ..This research program will be accompanied by comprehensive didactic sessions and strengthened by mentor/ collaborators and consultants that will enhance the investigator's skills and promote an independent career in academia. ..
  55. Formation of bile ducts in three dimensional culture
    Keith E Mostov; Fiscal Year: 2012
    ..The proposed work will greatly increase our understanding of early bile duct development and lead to improved health for patients with these diseases. ..
  56. The Role of Ikappa-B Kinase and Glycogen Synthase Kinase 3-beta in Axon Degenerat
    Josiah Gerdts; Fiscal Year: 2012
    ..This project will help us understand how damaged axons commit to self-destruction so that this process might be targeted by new therapies for nervous system diseases. ..
  57. Regulation of neurogenesis and behavior by GSK-3
    Peter S Klein; Fiscal Year: 2013
    ....
  58. Generation of a Transgenic Mouse Model for Functional Study of a Novel Gene FG01
    Huaxi Xu; Fiscal Year: 2010
    ..Moreover, the FG01 transgenic mouse model will have potential in developing novel diagnostic and therapeutic methods for multiple diseases including AD, diabetes and cancers. ..
  59. Effect of Adenosine A2 receptor activation on the mitochondrial death pathway
    Zhelong Xu; Fiscal Year: 2010
    ....
  60. SIGNALING MECHANISMS GOVERNING CARDIAC HYPERTROPHY
    Thomas Force; Fiscal Year: 2013
    ..The latter studies could lead to alternative strategies to traditional b-blockade, with the additional advantage that deletion (or inhibition) of GSK- 3a, unlike b-blockers, leads to improved glucose tolerance and insulin sensitivity. ..
  61. Inhibition of osteoblast function in bone erosion in rheumatoid arthritis
    Ellen M Gravallese; Fiscal Year: 2013
    ..Cellular sources of these factors will be identified in animal models in vivo. These studies are designed to identify novel targets for the augmentation of bone formation in RA. ..
  62. Validation of FGF14 as a New Molecular Target of GSK3
    Fernanda Laezza; Fiscal Year: 2013
    ..electrophysiological, and imaging assays, we provide breakthrough results showing a link between glycogen synthase kinase 3 (GSK3), a critical enzyme found dysfunctional in mood disorders, depression and schizophrenia, and ..
  63. DiosMemTM, a natural gamma-secretase inhibitor, opposes AD pathogenesis
    Jun Tan; Fiscal Year: 2009
    ..Among the many promising potential candidates are the glycogen synthase kinase 3 (GSK-3) inhibitors...
  64. Improving Gastrointestinal Recovery after Radiation
    George Georges; Fiscal Year: 2007
    ..Lithium specifically inhibits glycogen synthase kinase 3 beta (GSK-3[unreadable]) which activates intestinal stem cell proliferation via the wnt / [unreadable] ..
  65. Protein Kinase B and C in Head Injury
    Larry Jenkins; Fiscal Year: 2007
    ....
  66. Insulin and Oocyte Chromatin Segregation
    Gary Smith; Fiscal Year: 2009
    ..abstract_text> ..
  67. THE MOLECULAR BASIS OF AXIS FORMATION IN XENOPUS
    Janet Heasman; Fiscal Year: 2005
    ..This understanding is a prerequisite for the design of strategies for therapeutic interference with this pathway in anticancer treatment. ..
  68. NEURONAL CYTOSKELETAL ALTERATIONS IN ALZHEIMERS DISEASE
    Khalid Iqbal; Fiscal Year: 1999
    ..Identification of the protein kinase/s responsible far the abnormal phosphorylation in AD brain is critical to devise a rational approach in correcting this defect. ..
  69. REGULATION OF GLUCOCORTICOID RECEPTOR BY PHOSPHORYLATION
    Michael Garabedian; Fiscal Year: 2002
    ....