Gsk3a

Summary

Gene Symbol: Gsk3a
Description: glycogen synthase kinase 3 alpha
Alias: 2700086H06Rik, glycogen synthase kinase-3 alpha, GSK-3 alpha, serine/threonine-protein kinase GSK3A
Species: mouse
Products:     Gsk3a

Top Publications

  1. Kelly K, Ng D, Jayakumaran G, Wood G, Koide H, Doble B. ?-catenin enhances Oct-4 activity and reinforces pluripotency through a TCF-independent mechanism. Cell Stem Cell. 2011;8:214-27 pubmed publisher
    ..Collectively, our data suggest previously underappreciated, divergent TCF-dependent and TCF-independent roles for ?-catenin in ESCs. ..
  2. Steuber Buchberger P, Wurst W, Kühn R. Simultaneous Cre-mediated conditional knockdown of two genes in mice. Genesis. 2008;46:144-51 pubmed publisher
    ..We applied this technique to silence the widely coexpressed gene pairs Gsk-3alpha/Gsk-3beta and Erk1/Erk2 in murine embryonic stem cells and in the mouse brain. ..
  3. Matsuda T, Zhai P, Maejima Y, Hong C, Gao S, Tian B, et al. Distinct roles of GSK-3alpha and GSK-3beta phosphorylation in the heart under pressure overload. Proc Natl Acad Sci U S A. 2008;105:20900-5 pubmed publisher
  4. Bhavsar S, Merches K, Bobbala D, Lang F. AKT/SGK-sensitive phosphorylation of GSK3 in the regulation of L-selectin and perforin expression as well as activation induced cell death of T-lymphocytes. Biochem Biophys Res Commun. 2012;425:6-12 pubmed publisher
    ..In conclusion, PKB/Akt and SGK sensitive phosphorylation of GSK3?,? is a potent regulator of perforin expression and activation induced cell death in T lymphocytes. ..
  5. Li S, Mattar P, Zinyk D, Singh K, Chaturvedi C, Kovach C, et al. GSK3 temporally regulates neurogenin 2 proneural activity in the neocortex. J Neurosci. 2012;32:7791-805 pubmed publisher
    ..We thus conclude that the temporal regulation of Neurog2-E47 heterodimerization by GSK3 is a central component of the neuronal differentiation "clock" that coordinates the timing and tempo of neocortical neurogenesis in mouse. ..
  6. Hurtado D, Molina Porcel L, Carroll J, Macdonald C, Aboagye A, Trojanowski J, et al. Selectively silencing GSK-3 isoforms reduces plaques and tangles in mouse models of Alzheimer's disease. J Neurosci. 2012;32:7392-402 pubmed publisher
    ..These findings highlight the potential importance of GSK-3? as a possible therapeutic target for ameliorating behavioral impairments linked to AD SPs and NFTs. ..
  7. Webb I, Nishino Y, Clark J, Murdoch C, Walker S, Makowski M, et al. Constitutive glycogen synthase kinase-3alpha/beta activity protects against chronic beta-adrenergic remodelling of the heart. Cardiovasc Res. 2010;87:494-503 pubmed publisher
    ..Accordingly, strategies to prevent phosphorylation of Ser-21/9, and consequent inactivation of GSK-3alpha/beta, may enable a sustained cardiac response to chronic beta-agonist stimulation while preventing pathological remodelling. ..
  8. He F, Popkie A, Xiong W, Li L, Wang Y, Phiel C, et al. Gsk3? is required in the epithelium for palatal elevation in mice. Dev Dyn. 2010;239:3235-46 pubmed publisher
    ..Our results indicate that Gsk3? is an intrinsic regulator required in the epithelium for palate elevation, and could act through a pathway independent of Wnt/?-catenin signaling to regulate palate development...
  9. Force T, Woodgett J. Unique and overlapping functions of GSK-3 isoforms in cell differentiation and proliferation and cardiovascular development. J Biol Chem. 2009;284:9643-7 pubmed publisher
  10. Kim W, Wang X, Wu Y, Doble B, Patel S, Woodgett J, et al. GSK-3 is a master regulator of neural progenitor homeostasis. Nat Neurosci. 2009;12:1390-7 pubmed publisher
    ..Our results indicate that GSK-3 signaling is an essential mediator of homeostatic controls that regulate neural progenitors during mammalian brain development. ..

Detail Information

Publications86

  1. Kelly K, Ng D, Jayakumaran G, Wood G, Koide H, Doble B. ?-catenin enhances Oct-4 activity and reinforces pluripotency through a TCF-independent mechanism. Cell Stem Cell. 2011;8:214-27 pubmed publisher
    ..Collectively, our data suggest previously underappreciated, divergent TCF-dependent and TCF-independent roles for ?-catenin in ESCs. ..
  2. Steuber Buchberger P, Wurst W, Kühn R. Simultaneous Cre-mediated conditional knockdown of two genes in mice. Genesis. 2008;46:144-51 pubmed publisher
    ..We applied this technique to silence the widely coexpressed gene pairs Gsk-3alpha/Gsk-3beta and Erk1/Erk2 in murine embryonic stem cells and in the mouse brain. ..
  3. Matsuda T, Zhai P, Maejima Y, Hong C, Gao S, Tian B, et al. Distinct roles of GSK-3alpha and GSK-3beta phosphorylation in the heart under pressure overload. Proc Natl Acad Sci U S A. 2008;105:20900-5 pubmed publisher
  4. Bhavsar S, Merches K, Bobbala D, Lang F. AKT/SGK-sensitive phosphorylation of GSK3 in the regulation of L-selectin and perforin expression as well as activation induced cell death of T-lymphocytes. Biochem Biophys Res Commun. 2012;425:6-12 pubmed publisher
    ..In conclusion, PKB/Akt and SGK sensitive phosphorylation of GSK3?,? is a potent regulator of perforin expression and activation induced cell death in T lymphocytes. ..
  5. Li S, Mattar P, Zinyk D, Singh K, Chaturvedi C, Kovach C, et al. GSK3 temporally regulates neurogenin 2 proneural activity in the neocortex. J Neurosci. 2012;32:7791-805 pubmed publisher
    ..We thus conclude that the temporal regulation of Neurog2-E47 heterodimerization by GSK3 is a central component of the neuronal differentiation "clock" that coordinates the timing and tempo of neocortical neurogenesis in mouse. ..
  6. Hurtado D, Molina Porcel L, Carroll J, Macdonald C, Aboagye A, Trojanowski J, et al. Selectively silencing GSK-3 isoforms reduces plaques and tangles in mouse models of Alzheimer's disease. J Neurosci. 2012;32:7392-402 pubmed publisher
    ..These findings highlight the potential importance of GSK-3? as a possible therapeutic target for ameliorating behavioral impairments linked to AD SPs and NFTs. ..
  7. Webb I, Nishino Y, Clark J, Murdoch C, Walker S, Makowski M, et al. Constitutive glycogen synthase kinase-3alpha/beta activity protects against chronic beta-adrenergic remodelling of the heart. Cardiovasc Res. 2010;87:494-503 pubmed publisher
    ..Accordingly, strategies to prevent phosphorylation of Ser-21/9, and consequent inactivation of GSK-3alpha/beta, may enable a sustained cardiac response to chronic beta-agonist stimulation while preventing pathological remodelling. ..
  8. He F, Popkie A, Xiong W, Li L, Wang Y, Phiel C, et al. Gsk3? is required in the epithelium for palatal elevation in mice. Dev Dyn. 2010;239:3235-46 pubmed publisher
    ..Our results indicate that Gsk3? is an intrinsic regulator required in the epithelium for palate elevation, and could act through a pathway independent of Wnt/?-catenin signaling to regulate palate development...
  9. Force T, Woodgett J. Unique and overlapping functions of GSK-3 isoforms in cell differentiation and proliferation and cardiovascular development. J Biol Chem. 2009;284:9643-7 pubmed publisher
  10. Kim W, Wang X, Wu Y, Doble B, Patel S, Woodgett J, et al. GSK-3 is a master regulator of neural progenitor homeostasis. Nat Neurosci. 2009;12:1390-7 pubmed publisher
    ..Our results indicate that GSK-3 signaling is an essential mediator of homeostatic controls that regulate neural progenitors during mammalian brain development. ..
  11. Gillespie J, Ulici V, Dupuis H, Higgs A, DiMattia A, Patel S, et al. Deletion of glycogen synthase kinase-3? in cartilage results in up-regulation of glycogen synthase kinase-3? protein expression. Endocrinology. 2011;152:1755-66 pubmed publisher
    ..To our knowledge, this is the first tissue in which such a compensatory mechanism is described. Thus, our study provides important new insights into both skeletal development and the biology of GSK-3 proteins...
  12. Boini K, Amann K, Kempe D, Alessi D, Lang F. Proteinuria in mice expressing PKB/SGK-resistant GSK3. Am J Physiol Renal Physiol. 2009;296:F153-9 pubmed publisher
    ..The observations reveal that disruption of PKB/SGK-dependent regulation of GSK3 leads to glomerular injury with proteinuria, which may at least partially be secondary to enhanced blood pressure. ..
  13. Nishino Y, Webb I, Davidson S, Ahmed A, Clark J, Jacquet S, et al. Glycogen synthase kinase-3 inactivation is not required for ischemic preconditioning or postconditioning in the mouse. Circ Res. 2008;103:307-14 pubmed publisher
    ..Our results, which include a novel genetic approach, suggest that the inhibition of GSK-3 is unlikely to be the key determinant of cardioprotective signaling in either preconditioning or postconditioning in the mouse. ..
  14. Zhou J, Lal H, Chen X, Shang X, Song J, Li Y, et al. GSK-3alpha directly regulates beta-adrenergic signaling and the response of the heart to hemodynamic stress in mice. J Clin Invest. 2010;120:2280-91 pubmed publisher
    ..b>Gsk3a(-/-) mice over 2 months of age developed progressive cardiomyocyte and cardiac hypertrophy and contractile ..
  15. Doble B, Patel S, Wood G, Kockeritz L, Woodgett J. Functional redundancy of GSK-3alpha and GSK-3beta in Wnt/beta-catenin signaling shown by using an allelic series of embryonic stem cell lines. Dev Cell. 2007;12:957-71 pubmed
    ..The rheostatic regulation of GSK-3 highlights the importance of considering the contributions of both homologs when studying GSK-3 functions in mammalian systems. ..
  16. MacAulay K, Doble B, Patel S, Hansotia T, Sinclair E, Drucker D, et al. Glycogen synthase kinase 3alpha-specific regulation of murine hepatic glycogen metabolism. Cell Metab. 2007;6:329-37 pubmed
    ..We conclude that GSK-3 isoforms exhibit tissue-specific physiological functions and that GSK-3alpha KO mice are insulin sensitive, reinforcing the potential of GSK-3 as a therapeutic target for type II diabetes. ..
  17. Zhai P, Gao S, Holle E, Yu X, Yatani A, Wagner T, et al. Glycogen synthase kinase-3alpha reduces cardiac growth and pressure overload-induced cardiac hypertrophy by inhibition of extracellular signal-regulated kinases. J Biol Chem. 2007;282:33181-91 pubmed
    ..The anti-hypertrophic and pro-apoptotic effect of GSK-3alpha is mediated through inhibition of ERK. ..
  18. Kim W, Zhou F, Zhou J, Yokota Y, Wang Y, Yoshimura T, et al. Essential roles for GSK-3s and GSK-3-primed substrates in neurotrophin-induced and hippocampal axon growth. Neuron. 2006;52:981-96 pubmed
    ..Our results suggest that GSK-3 is a downstream convergent point for many axon growth regulatory pathways and that differential regulation of primed versus all GSK-3 substrates is associated with a specific morphological outcome. ..
  19. Mora A, Sakamoto K, McManus E, Alessi D. Role of the PDK1-PKB-GSK3 pathway in regulating glycogen synthase and glucose uptake in the heart. FEBS Lett. 2005;579:3632-8 pubmed
  20. Beurel E, Yeh W, Michalek S, Harrington L, Jope R. Glycogen synthase kinase-3 is an early determinant in the differentiation of pathogenic Th17 cells. J Immunol. 2011;186:1391-8 pubmed publisher
    ..These findings identify GSK3 as a critical mediator of Th17 cell production and indicate that GSK3 inhibitors provide a potential therapeutic intervention to control Th17-mediated diseases. ..
  21. Kaidanovich Beilin O, Lipina T, Takao K, van Eede M, Hattori S, Laliberte C, et al. Abnormalities in brain structure and behavior in GSK-3alpha mutant mice. Mol Brain. 2009;2:35 pubmed publisher
    ..Taken together, these data support a role for the GSK-3alpha gene in CNS functioning and possible involvement in the development of psychiatric disorders. ..
  22. McManus E, Sakamoto K, Armit L, Ronaldson L, Shpiro N, Marquez R, et al. Role that phosphorylation of GSK3 plays in insulin and Wnt signalling defined by knockin analysis. EMBO J. 2005;24:1571-83 pubmed
    ..These results establish the function of Ser21/Ser9 phosphorylation in several processes in which GSK3 inactivation has previously been implicated. ..
  23. Eom T, Jope R. Blocked inhibitory serine-phosphorylation of glycogen synthase kinase-3alpha/beta impairs in vivo neural precursor cell proliferation. Biol Psychiatry. 2009;66:494-502 pubmed publisher
  24. Beurel E, Jope R. Glycogen synthase kinase-3 regulates inflammatory tolerance in astrocytes. Neuroscience. 2010;169:1063-70 pubmed publisher
    ..These findings identify the critical role of GSK3 in counteracting IL-6 inflammatory tolerance in cells of the CNS, supporting the therapeutic potential of GSK3 inhibitors to reduce neuroinflammation by promoting tolerance. ..
  25. Wang Z, Iwasaki M, Ficara F, Lin C, Matheny C, Wong S, et al. GSK-3 promotes conditional association of CREB and its coactivators with MEIS1 to facilitate HOX-mediated transcription and oncogenesis. Cancer Cell. 2010;17:597-608 pubmed publisher
  26. Miyamoto S, Purcell N, Smith J, Gao T, Whittaker R, Huang K, et al. PHLPP-1 negatively regulates Akt activity and survival in the heart. Circ Res. 2010;107:476-84 pubmed publisher
    ..These results implicate PHLPP-1 as an endogenous negative regulator of Akt activity and cell survival in the heart. ..
  27. Zhong Z, Wang Y, Guo H, Sagare A, Fernandez J, Bell R, et al. Protein S protects neurons from excitotoxic injury by activating the TAM receptor Tyro3-phosphatidylinositol 3-kinase-Akt pathway through its sex hormone-binding globulin-like region. J Neurosci. 2010;30:15521-34 pubmed publisher
  28. Hey F, Giblett S, Forrest S, Herbert C, Pritchard C. Phosphorylations of Serines 21/9 in Glycogen Synthase Kinase 3?/? Are Not Required for Cell Lineage Commitment or WNT Signaling in the Normal Mouse Intestine. PLoS ONE. 2016;11:e0156877 pubmed publisher
    ..Our results provide in vivo evidence that GSK3 is regulated through mechanisms independent of N-terminal serine phosphorylation in order for ?-catenin to be stabilised. ..
  29. Zhao Y, Altman B, Coloff J, Herman C, Jacobs S, Wieman H, et al. Glycogen synthase kinase 3alpha and 3beta mediate a glucose-sensitive antiapoptotic signaling pathway to stabilize Mcl-1. Mol Cell Biol. 2007;27:4328-39 pubmed
  30. Eom T, Roth K, Jope R. Neural precursor cells are protected from apoptosis induced by trophic factor withdrawal or genotoxic stress by inhibitors of glycogen synthase kinase 3. J Biol Chem. 2007;282:22856-64 pubmed
    ..Thus, NPCs are sensitive to loss of trophic factors and genotoxic stress, and inhibitors of GSK3 are capable of enhancing NPC survival. ..
  31. Barrell W, Szabo Rogers H, Liu K. Novel reporter alleles of GSK-3? and GSK-3?. PLoS ONE. 2012;7:e50422 pubmed publisher
    ..Finally, we observed gestational lethality in compound GSK-3?(-/-); GSK3?(+/-) mutants, suggesting that GSK-3 dosage is critical during embryonic development. ..
  32. Maejima Y, Galeotti J, Molkentin J, Sadoshima J, Zhai P. Constitutively active MEK1 rescues cardiac dysfunction caused by overexpressed GSK-3? during aging and hemodynamic pressure overload. Am J Physiol Heart Circ Physiol. 2012;303:H979-88 pubmed publisher
    ..In conclusion, inhibition of the MEK1/ERK pathway mediates the hypertrophy suppression and cardiac dysfunction caused by GSK-3? overexpression in cardiac myocytes. ..
  33. Patel S, MacAulay K, Woodgett J. Tissue-specific analysis of glycogen synthase kinase-3? (GSK-3?) in glucose metabolism: effect of strain variation. PLoS ONE. 2011;6:e15845 pubmed publisher
    ..We surmise that the insulin-sensitization observed in the out-bred strain of mice lacking GSK-3? is mediated by indirect means that do not require intrinsic function of GSK-3? in skeletal muscle and liver tissues. ..
  34. Polter A, Beurel E, Yang S, Garner R, Song L, Miller C, et al. Deficiency in the inhibitory serine-phosphorylation of glycogen synthase kinase-3 increases sensitivity to mood disturbances. Neuropsychopharmacology. 2010;35:1761-74 pubmed publisher
  35. Umans L, Vermeire L, Francis A, Chang H, Huylebroeck D, Zwijsen A. Generation of a floxed allele of Smad5 for cre-mediated conditional knockout in the mouse. Genesis. 2003;37:5-11 pubmed
    ..Smad5(flE2/flE2) mice are now available and will be a valuable tool to analyze the role of Smad5 beyond its crucial early embryonic function throughout development and postnatal life. ..
  36. Yamamoto H, Yoo S, Nishita M, Kikuchi A, Minami Y. Wnt5a modulates glycogen synthase kinase 3 to induce phosphorylation of receptor tyrosine kinase Ror2. Genes Cells. 2007;12:1215-23 pubmed
    ..Moreover, it was found that Wnt5a-induced cell migration can be inhibited by SB216763 or by siRNA-mediated suppression of GSK-3alpha (and GSK-3beta) expression, further emphasizing the role(s) of GSK-3 in Wnt5a-induced signaling. ..
  37. Hur E, Saijilafu -, Lee B, Kim S, Xu W, Zhou F. GSK3 controls axon growth via CLASP-mediated regulation of growth cone microtubules. Genes Dev. 2011;25:1968-81 pubmed publisher
    ..We propose a model in which CLASP transduces GSK3 activity levels to differentially control axon growth by coordinating the stability and configuration of growth cone MTs. ..
  38. Micsenyi A, Tan X, Sneddon T, Luo J, Michalopoulos G, Monga S. Beta-catenin is temporally regulated during normal liver development. Gastroenterology. 2004;126:1134-46 pubmed
    ..Nuclear and cytoplasmic beta-catenin corresponded to cell proliferation in liver development. Finally, a smaller-molecular-weight species of beta-catenin might be maintaining normal interactions at the membrane. ..
  39. Itoh S, Saito T, Hirata M, Ushita M, Ikeda T, Woodgett J, et al. GSK-3? and GSK-3? proteins are involved in early stages of chondrocyte differentiation with functional redundancy through RelA protein phosphorylation. J Biol Chem. 2012;287:29227-36 pubmed publisher
    ..Although knock-out of both alleles of Gsk3a (Gsk3a(-/-)) or a single allele of Gsk3b (Gsk3b(+/-)) in mice did not significantly affect skeletal development, ..
  40. Spokoini R, Kfir Erenfeld S, Yefenof E, Sionov R. Glycogen synthase kinase-3 plays a central role in mediating glucocorticoid-induced apoptosis. Mol Endocrinol. 2010;24:1136-50 pubmed publisher
    ..Our data suggest that targeting protein kinases involved in GSK3 inactivation should improve the outcome of GC therapy. ..
  41. Deng Y, Xiong Z, Chen P, Wei J, Chen S, Yan Z. ?-amyloid impairs the regulation of N-methyl-D-aspartate receptors by glycogen synthase kinase 3. Neurobiol Aging. 2014;35:449-59 pubmed publisher
    ..Consequently, GSK-3 inhibitor lost the capability of protecting neurons against N-methyl-D-aspartate-induced excitotoxicity in A?-treated neurons. These results have provided a novel mechanism underlying the involvement of GSK-3 in AD. ..
  42. Beurel E, Jope R. Glycogen synthase kinase-3 promotes the synergistic action of interferon-gamma on lipopolysaccharide-induced IL-6 production in RAW264.7 cells. Cell Signal. 2009;21:978-85 pubmed publisher
    ..These results demonstrate the dependency of macrophage priming by IFN-gamma on STAT3 and GSK3, providing novel targets for intervention. ..
  43. Lee F, Kaidanovich Beilin O, Roder J, Woodgett J, Wong A. Genetic inactivation of GSK3? rescues spine deficits in Disc1-L100P mutant mice. Schizophr Res. 2011;129:74-9 pubmed publisher
    ..These findings suggest novel treatment approaches for schizophrenia, and identify a histological read-out for testing other therapeutic interventions. ..
  44. Gulen M, Bulek K, Xiao H, Yu M, Gao J, Sun L, et al. Inactivation of the enzyme GSK3? by the kinase IKKi promotes AKT-mTOR signaling pathway that mediates interleukin-1-induced Th17 cell maintenance. Immunity. 2012;37:800-12 pubmed publisher
    ..Thus, IKKi has a critical role in Th17 cell maintenance and/or proliferation through the GSK-AKT-mTOR pathway, implicating the potential of IKKi as a therapeutic target. ..
  45. Pilot Storck F, Chopin E, Rual J, Baudot A, Dobrokhotov P, Robinson Rechavi M, et al. Interactome mapping of the phosphatidylinositol 3-kinase-mammalian target of rapamycin pathway identifies deformed epidermal autoregulatory factor-1 as a new glycogen synthase kinase-3 interactor. Mol Cell Proteomics. 2010;9:1578-93 pubmed publisher
    ..deformed epidermal autoregulatory factor-1 (DEAF1) transcription factor as an interactor and in vitro substrate of GSK3A and GSK3B...
  46. Paul J, Johnson R, Jope R, Gamble K. Disruption of circadian rhythmicity and suprachiasmatic action potential frequency in a mouse model with constitutive activation of glycogen synthase kinase 3. Neuroscience. 2012;226:1-9 pubmed publisher
    ..Because GSK3 has been implicated in numerous pathologies, understanding how GSK3 modulates circadian rhythms and neurophysiological activity may lead to novel therapeutics for pathological disorders and circadian rhythm dysfunction. ..
  47. Zhou J, Freeman T, Ahmad F, Shang X, Mangano E, Gao E, et al. GSK-3? is a central regulator of age-related pathologies in mice. J Clin Invest. 2013;123:1821-32 pubmed publisher
    ..Herein, we demonstrate premature death and acceleration of age-related pathologies in the Gsk3a global KO mouse...
  48. Banko N, McAlpine C, Venegas Pino D, Raja P, Shi Y, Khan M, et al. Glycogen synthase kinase 3? deficiency attenuates atherosclerosis and hepatic steatosis in high fat diet-fed low density lipoprotein receptor-deficient mice. Am J Pathol. 2014;184:3394-404 pubmed publisher
    ..We crossed Gsk3a/GSK3?-knockout mice with low-density lipoprotein receptor (Ldlr) knockout mice...
  49. Lipina C, Huang X, Finlay D, McManus E, Alessi D, Sutherland C. Analysis of hepatic gene transcription in mice expressing insulin-insensitive GSK3. Biochem J. 2005;392:633-9 pubmed
    ..We suggest for the first time that although pharmacological inhibition of GSK3 reduces hepatic glucose production even in insulin-resistant states, feeding can repress the gluconeogenic genes without inhibiting GSK3. ..
  50. Goñi Oliver P, Lucas J, Avila J, Hernandez F. N-terminal cleavage of GSK-3 by calpain: a new form of GSK-3 regulation. J Biol Chem. 2007;282:22406-13 pubmed
    ..These data provide the first direct evidence that calpain promotes GSK-3 truncation in a way that has implications in signal transduction, and probably in pathological disorders such as Alzheimer disease. ..
  51. Wray J, Kalkan T, Gómez López S, Eckardt D, Cook A, Kemler R, et al. Inhibition of glycogen synthase kinase-3 alleviates Tcf3 repression of the pluripotency network and increases embryonic stem cell resistance to differentiation. Nat Cell Biol. 2011;13:838-45 pubmed publisher
    ..We conclude that Gsk3 inhibition stabilizes the embryonic stem cell state primarily by reducing repressive influence on the core pluripotency network. ..
  52. Beaulieu J, Sotnikova T, Marion S, Lefkowitz R, Gainetdinov R, Caron M. An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell. 2005;122:261-73 pubmed
  53. Charvet C, Wissler M, Brauns Schubert P, Wang S, Tang Y, Sigloch F, et al. Phosphorylation of Tip60 by GSK-3 determines the induction of PUMA and apoptosis by p53. Mol Cell. 2011;42:584-96 pubmed publisher
    ..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. ..
  54. Chen M, Maloney J, Kallop D, Atwal J, Tam S, Baer K, et al. Spatially coordinated kinase signaling regulates local axon degeneration. J Neurosci. 2012;32:13439-53 pubmed
    ..Additionally, we identify the dleu2/mir15a/16-1 cluster, previously characterized as a regulator of B-cell proliferation, and the transcription factor tbx6, as likely downstream effectors of GSK3? in axon degeneration. ..
  55. Ahn J, Jang J, Choi J, Lee J, Oh S, Lee J, et al. GSK3?, but not GSK3?, inhibits the neuronal differentiation of neural progenitor cells as a downstream target of mammalian target of rapamycin complex1. Stem Cells Dev. 2014;23:1121-33 pubmed publisher
    ..Taken together, our results demonstrate that GSK3?, but not GSK3?, negatively controls the neuronal differentiation of progenitor cells and that GSK3? may act downstream of the mammalian target of rapamycin complex1 signaling pathway. ..
  56. Partovian C, Ju R, Zhuang Z, Martin K, Simons M. Syndecan-4 regulates subcellular localization of mTOR Complex2 and Akt activation in a PKCalpha-dependent manner in endothelial cells. Mol Cell. 2008;32:140-9 pubmed publisher
    ..Thus, S4-dependent targeting of PKCalpha to the plasma membrane is required for recruitment of mTORC2 components to the rafts and Akt activation. ..
  57. Yokota Y, Eom T, Stanco A, Kim W, Rao S, Snider W, et al. Cdc42 and Gsk3 modulate the dynamics of radial glial growth, inter-radial glial interactions and polarity in the developing cerebral cortex. Development. 2010;137:4101-10 pubmed publisher
    ..Related cell polarity determinants (Cdc42, Gsk3) differentially influence radial glial activities within the evolving radial glia scaffold to coordinate the formation of cerebral cortex. ..
  58. Webb I, Sicard P, Clark J, Redwood S, Marber M. Myocardial stress remodelling after regional infarction is independent of glycogen synthase kinase-3 inactivation. J Mol Cell Cardiol. 2010;49:897-900 pubmed publisher
    ..This highlights the heterogeneity of pathological hypertrophy and the divergent role of GSK-3 signalling in chronic myocardial stress. ..
  59. Beurel E, Song L, Jope R. Inhibition of glycogen synthase kinase-3 is necessary for the rapid antidepressant effect of ketamine in mice. Mol Psychiatry. 2011;16:1068-70 pubmed publisher
  60. Hasumi Y, Baba M, Ajima R, Hasumi H, Valera V, Klein M, et al. Homozygous loss of BHD causes early embryonic lethality and kidney tumor development with activation of mTORC1 and mTORC2. Proc Natl Acad Sci U S A. 2009;106:18722-7 pubmed publisher
  61. Shinohara M, Ybanez M, Win S, Than T, Jain S, Gaarde W, et al. Silencing glycogen synthase kinase-3beta inhibits acetaminophen hepatotoxicity and attenuates JNK activation and loss of glutamate cysteine ligase and myeloid cell leukemia sequence 1. J Biol Chem. 2010;285:8244-55 pubmed publisher
    ..Taken together our results suggest that activation of GSK-3beta is a key mediator of the initial phase of APAP-induced liver injury through modulating GCL and Mcl-1 degradation, as well as JNK activation in liver. ..
  62. Vertino A, Taylor Jones J, Longo K, Bearden E, Lane T, McGehee R, et al. Wnt10b deficiency promotes coexpression of myogenic and adipogenic programs in myoblasts. Mol Biol Cell. 2005;16:2039-48 pubmed
    ..Thus, alteration in Wnt signaling in myoblasts with age may contribute to impaired muscle regenerative capacity and to increased muscle adiposity, both characteristic of aged muscle. ..
  63. Baki L, Shioi J, Wen P, Shao Z, Schwarzman A, Gama Sosa M, et al. PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations. EMBO J. 2004;23:2586-96 pubmed
    ..Our data raise the possibility that PS1 may prevent development of AD pathology by activating the PI3K/Akt signaling pathway. In contrast, FAD mutations may promote AD pathology by inhibiting this pathway. ..
  64. Morgan Smith M, Wu Y, Zhu X, Pringle J, Snider W. GSK-3 signaling in developing cortical neurons is essential for radial migration and dendritic orientation. elife. 2014;3:e02663 pubmed publisher
    ..DOI: http://dx.doi.org/10.7554/eLife.02663.001. ..
  65. Ka M, Jung E, Mueller U, Kim W. MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling. Dev Biol. 2014;395:4-18 pubmed publisher
    ..Our findings establish a cellular mechanism underlying neuronal migration and provide insights into the regulation of cytoskeleton dynamics in developing neurons. ..
  66. Zhang B, Saijilafu -, Liu C, Wang R, Zhu Q, Jiao Z, et al. Akt-independent GSK3 inactivation downstream of PI3K signaling regulates mammalian axon regeneration. Biochem Biophys Res Commun. 2014;443:743-8 pubmed publisher
    ..Together, these results indicate that in response to peripheral nerve injury GSK3 inactivation, regulated by an alternative mechanism independent of Akt-mediated phosphorylation, controls sensory axon regeneration. ..
  67. Bouskila M, Hunter R, Ibrahim A, Delattre L, Peggie M, van Diepen J, et al. Allosteric regulation of glycogen synthase controls glycogen synthesis in muscle. Cell Metab. 2010;12:456-66 pubmed publisher
    ..Our study provides genetic evidence that allosteric activation of GS is the primary mechanism by which insulin promotes muscle glycogen accumulation in vivo. ..
  68. Cho J, Rameshwar P, Sadoshima J. Distinct roles of glycogen synthase kinase (GSK)-3alpha and GSK-3beta in mediating cardiomyocyte differentiation in murine bone marrow-derived mesenchymal stem cells. J Biol Chem. 2009;284:36647-58 pubmed publisher
    ..GSK-3beta in the cytosol induces CM differentiation of MSCs through down-regulation of beta-catenin. In contrast, GSK-3alpha in the nucleus inhibits CM differentiation through down-regulation of c-Jun. ..
  69. Zhang M, Zhang J, Chen X, Cho S, Chen X. Glycogen synthase kinase 3 promotes p53 mRNA translation via phosphorylation of RNPC1. Genes Dev. 2013;27:2246-58 pubmed publisher
    ..Together, we postulate that the p53-RNPC1 loop can be explored to increase or decrease p53 activity for cancer therapy. ..
  70. Rotte A, Pasham V, Eichenmüller M, Yang W, Qadri S, Bhandaru M, et al. Regulation of basal gastric acid secretion by the glycogen synthase kinase GSK3. J Gastroenterol. 2010;45:1022-32 pubmed publisher
    ..PKB/Akt phosphorylates glycogen synthase kinase GSK3. The present study explored whether PKB/Akt-dependent GSK3-phosphorylation modifies gastric acid secretion...
  71. Giambelluca M, Bertheau Mailhot G, Laflamme C, Rollet Labelle E, Servant M, Pouliot M. TNF-? expression in neutrophils and its regulation by glycogen synthase kinase-3: a potentiating role for lithium. FASEB J. 2014;28:3679-90 pubmed publisher
  72. Bouskila M, Hirshman M, Jensen J, Goodyear L, Sakamoto K. Insulin promotes glycogen synthesis in the absence of GSK3 phosphorylation in skeletal muscle. Am J Physiol Endocrinol Metab. 2008;294:E28-35 pubmed
    ..This suggests that allosteric regulation of GS by G-6-P may play a key role in insulin-stimulated muscle glycogen synthesis in vivo. ..
  73. Gobrecht P, Leibinger M, Andreadaki A, Fischer D. Sustained GSK3 activity markedly facilitates nerve regeneration. Nat Commun. 2014;5:4561 pubmed publisher
    ..Therefore, suppression of this internal 'regenerative break' may potentially provide a new perspective for the clinical treatment of nerve injuries...
  74. McAlpine C, Werstuck G. Protein kinase R-like endoplasmic reticulum kinase and glycogen synthase kinase-3?/? regulate foam cell formation. J Lipid Res. 2014;55:2320-33 pubmed publisher
    ..These findings suggest that ER stress-PERK-GSK3?/? signaling promotes proatherogenic macrophage lipid accumulation. ..
  75. Dembowy J, Adissu H, Liu J, Zacksenhaus E, Woodgett J. Effect of glycogen synthase kinase-3 inactivation on mouse mammary gland development and oncogenesis. Oncogene. 2015;34:3514-26 pubmed publisher
    ..Collectively, these results establish the two isoforms of GSK-3 as essential integrators of multiple developmental signals that act to maintain normal mammary gland function and suppress tumorigenesis. ..
  76. Mines M, Yuskaitis C, King M, Beurel E, Jope R. GSK3 influences social preference and anxiety-related behaviors during social interaction in a mouse model of fragile X syndrome and autism. PLoS ONE. 2010;5:e9706 pubmed publisher
    ..As discussed in the present work, these results suggest a role for GSK3 in social behaviors and implicate inhibition of GSK3 as a potential therapeutic. ..
  77. Wu C, Chen P, Yeh S. Nucleocapsid phosphorylation and RNA helicase DDX1 recruitment enables coronavirus transition from discontinuous to continuous transcription. Cell Host Microbe. 2014;16:462-72 pubmed publisher
    ..Thus, coronaviruses employ a unique strategy for the transition from discontinuous to continuous transcription to ensure balanced sgmRNAs and full-length gRNA synthesis...
  78. Gómez Sintes R, Hernandez F, Bortolozzi A, Artigas F, Avila J, Zaratin P, et al. Neuronal apoptosis and reversible motor deficit in dominant-negative GSK-3 conditional transgenic mice. EMBO J. 2007;26:2743-54 pubmed
    ..Interestingly, the reversibility data also suggest that unwanted side effects are likely to revert if excessive GSK-3 inhibition is halted. ..
  79. Kawasaki Y, Kugimiya F, Chikuda H, Kamekura S, Ikeda T, Kawamura N, et al. Phosphorylation of GSK-3beta by cGMP-dependent protein kinase II promotes hypertrophic differentiation of murine chondrocytes. J Clin Invest. 2008;118:2506-15 pubmed publisher
    ..These data indicate that hypertrophic differentiation of growth plate chondrocytes during skeletal growth is promoted by phosphorylation and inactivation of GSK-3beta by cGKII. ..
  80. Lal H, Zhou J, Ahmad F, Zaka R, Vagnozzi R, Decaul M, et al. Glycogen synthase kinase-3? limits ischemic injury, cardiac rupture, post-myocardial infarction remodeling and death. Circulation. 2012;125:65-75 pubmed publisher
    ..These findings are in striking contrast to multiple previous reports in which deletion or inhibition of GSK-3? is protective. ..
  81. Waraich R, Weigert C, Kalbacher H, Hennige A, Lutz S, Haring H, et al. Phosphorylation of Ser357 of rat insulin receptor substrate-1 mediates adverse effects of protein kinase C-delta on insulin action in skeletal muscle cells. J Biol Chem. 2008;283:11226-33 pubmed publisher
    ..Together, these data suggest that phosphorylation of Ser(357) mediates at least in part the adverse effects of PKC-delta activation on insulin action. ..
  82. Garrido J, Simon D, Varea O, Wandosell F. GSK3 alpha and GSK3 beta are necessary for axon formation. FEBS Lett. 2007;581:1579-86 pubmed
    ..Moreover, interference RNAs impeding the expression of the GSK3 alpha or beta isoforms in hippocampal neurons prevents an axon from forming. ..
  83. Pardo M, King M, Perez Costas E, Melendez Ferro M, Martinez A, Beurel E, et al. Impairments in cognition and neural precursor cell proliferation in mice expressing constitutively active glycogen synthase kinase-3. Front Behav Neurosci. 2015;9:55 pubmed publisher