GSK3 signalling in neural development

Nature Reviews Neuroscience

Volumn 11, Issue 8, 2010, Pages 539-551

  Hur, Eun Mi ^a   Zhou, Feng Quan ^a,b  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b 215 Ross Research Building ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEIN; GLYCOGEN SYNTHASE KINASE 3; PROTEIN PAR 6; PROTEINASE ACTIVATED RECEPTOR 3; UNCLASSIFIED DRUG; WNT PROTEIN;

BRAIN DEVELOPMENT; CELL DIFFERENTIATION; CELL PROLIFERATION; DENDRITE; HUMAN; MICROTUBULE; NERVE CELL DIFFERENTIATION; NERVE FIBER GROWTH; NERVE GROWTH; NERVOUS SYSTEM; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; POLARIZATION; PRIORITY JOURNAL; PROTEIN DEGRADATION; REVIEW; SCHIZOPHRENIA; SIGNAL TRANSDUCTION;

ANIMALS; BRAIN; GLYCOGEN SYNTHASE KINASE 3; HUMANS; ISOENZYMES; NEUROGENESIS; NEURONS; SIGNAL TRANSDUCTION;

EID: 77954874401     PISSN: 1471003X     EISSN: 14710048     Source Type: Journal    
DOI: 10.1038/nrn2870     Document Type: Review

References (131)

1. Woodgett, J. R. & Cohen, P. Multisite phosphorylation of glycogen synthase. Molecular basis for the substrate specificity of glycogen synthase kinase-3 and casein kinase-II (glycogen synthase kinase-5). Biochim. Biophys. Acta 788, 339-347 (1984).
2. Wang, Y. & Roach, P. J. Inactivation of rabbit muscle glycogen synthase by glycogen synthase kinase-3. Dominant role of the phosphorylation of Ser-640 (site-3a). J. Biol. Chem. 268, 23876-23880 (1993).
3. Woodgett, J. R. Molecular cloning and expression of glycogen synthase kinase-3/factor A. EMBO J. 9, 2431-2438 (1990).
4. Mukai, F., Ishiguro, K., Sano, Y. & Fujita, S. C. Alternative splicing isoform of tau protein kinase I/glycogen synthase kinase 3β. J. Neurochem. 81, 1073-1083 (2002).
5. Castano, Z., Gordon-Weeks, P. R. & Kypta, R. M. The neuron-specific isoform of glycogen synthase kinase-3β is required for axon growth. J. Neurochem. 11 3, 117-130 (2010).
6. Wood-Kaczmar, A., Kraus, M., Ishiguro, K., Philpott, K. L. & Gordon-Weeks, P. R. An alternatively spliced form of glycogen synthase kinase-3β is targeted to growing neurites and growth cones. Mol. Cell. Neurosci. 42, 184-194 (2009).
7. Woodgett, J. R. Judging a protein by more than its name: GSK-3. Sci. STKE 2001, re12 (2001).
8. Grimes, C. A. & Jope, R. S. CREB DNA binding activity is inhibited by glycogen synthase kinase-3 β and facilitated by lithium. J. Neurochem. 78, 1219-1232 (2001).
9. Beals, C. R., Sheridan, C. M., Turck, C. W., Gardner, P. & Crabtree, G. R. Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3. Science 275, 1930-1934 (1997).
10. Neal, J. W. & Clipstone, N. A. Glycogen synthase kinase-3 inhibits the DNA binding activity of NFATc. J. Biol. Chem. 276, 3666-3673 (2001).
11. Ma, Y. C. et al. Regulation of motor neuron specification by phosphorylation of neurogenin 2. Neuron 58, 65-77 (2008).
12. Fuentealba, L. C. et al. Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal. Cell 131, 980-993 (2007).
13. de Groot, R. P., Auwerx, J., Bourouis, M. & Sassone-Corsi, P. Negative regulation of Jun/AP-1: conserved function of glycogen synthase kinase 3 and the Drosophila kinase shaggy. Oncogene 8, 841-847 (1993). (Pubitemid 23087414)
14. Aberle, H., Bauer, A., Stappert, J., Kispert, A. & Kemler, R. β-catenin is a target for the ubiquitin-proteasome pathway. EMBO J. 16, 3797-3804 (1997).
15. Zhou, F. Q. & Snider, W. D. Cell biology. GSK-3β and microtubule assembly in axons. Science 308, 211-214 (2005).
16. Beaulieu, J. M. Not only lithium: regulation of glycogen synthase kinase-3 by antipsychotics and serotonergic drugs. Int. J. Neuropsychopharmacol. 10, 3-6 (2007).
17. Beaulieu, J. M., Gainetdinov, R. R. & Caron, M. G. Akt/GSK3 signaling in the action of psychotropic drugs. Annu. Rev. Pharmacol. Toxicol. 49, 327-347 (2009).
18. Klein, P. S. & Melton, D. A. A molecular mechanism for the effect of lithium on development. Proc. Natl Acad. Sci. USA 93, 8455-8459 (1996).
19. Martinez, A. Preclinical efficacy on GSK-3 inhibitors: towards a future generation of powerful drugs. Med. Res. Rev. 28, 773-796 (2008).
20. Lovestone, S., Killick, R., Di Forti, M. & Murray, R. Schizophrenia as a GSK-3 dysregulation disorder. Trends Neurosci. 30, 142-149 (2007).
21. Kwon, C. H. et al. Pten regulates neuronal arborization and social interaction in mice. Neuron 50, 377-388 (2006).
22. Mao, Y. et al. Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3β/β-catenin signaling. Cell 136, 1017-1031 (2009).
23. Beaulieu, J. M. et al. Role of GSK3 β in behavioral abnormalities induced by serotonin deficiency. Proc. Natl Acad. Sci. USA 105, 1333-1338 (2008).
24. Zhang, H. H., Lipovsky, A. I., Dibble, C. C., Sahin, M. & Manning, B. D. S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition of Akt. Mol. Cell 24, 185-197 (2006).
25. Zhou, X. L. et al. Association of adenomatous polyposis coli (APC) gene polymorphisms with autism spectrum disorder (ASD). Am. J. Med. Genet. B Neuropsychiatr. Genet. 144B, 351-354 (2007).
26. Mili, S., Moissoglu, K. & Macara, I. G. Genome-wide screen reveals APC-associated RNAs enriched in cell protrusions. Nature 453, 115-119 (2008).
27. Cross, D. A., Alessi, D. R., Cohen, P., Andjelkovich, M. & Hemmings, B. A. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378, 785-789 (1995).
28. Frame, S. & Cohen, P. GSK3 takes centre stage more than 20 years after its discovery. Biochem. J. 359, 1-16 (2001).
29. McManus, E. J. et al. Role that phosphorylation of GSK3 plays in insulin and Wnt signalling defined by knockin analysis. EMBO J. 24, 1571-1583 (2005).
30. Thornton, T. M. et al. Phosphorylation by p38 MAPK as an alternative pathway for GSK3β inactivation. Science 320, 667-670 (2008).
31. Kim, W. Y. et al. Essential roles for GSK-3s and GSK-3-primed substrates in neurotrophin-induced and hippocampal axon growth. Neuron 52, 981-996 (2006).
32. Piao, S. et al. Direct inhibition of GSK3β by the phosphorylated cytoplasmic domain of LRP6 in Wnt/β-catenin signaling. PLoS ONE 3, e4046 (2008).
33. Wu, G., Huang, H., Garcia Abreu, J. & He, X. Inhibition of GSK3 phosphorylation of β-catenin via phosphorylated PPPSPXS motifs of Wnt coreceptor LRP6. PLoS ONE 4, e4926 (2009).
34. Wu, X. et al. Cdc42 controls progenitor cell differentiation and β-catenin turnover in skin. Genes D e v. 20, 571-585 (2006).
35. Hengst, U., Deglincerti, A., Kim, H. J., Jeon, N. L. & Jaffrey, S. R. Axonal elongation triggered by stimulus-induced local translation of a polarity complex protein. Nature Cell Biol. 11, 1024-1030 (2009).
36. Etienne-Manneville, S. & Hall, A. Cdc42 regulates GSK-3β and adenomatous polyposis coli to control cell polarity. Nature 421, 753-756 (2003).
37. Schlessinger, K., McManus, E. J. & Hall, A. Cdc42 and noncanonical Wnt signal transduction pathways cooperate to promote cell polarity. J. Cell Biol. 178, 355-361 (2007).
38. Itoh, N. et al. Identification of focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3-kinase) as Par3 partners by proteomic analysis. Cytoskeleton (Hoboken) 67, 297-308 (2010).
39. Kim, W. Y. et al. GSK-3 is a master regulator of neural progenitor homeostasis. Nature Neurosci. 12, 1390-1397 (2009).
40. Bultje, R. S. et al. Mammalian Par3 regulates progenitor cell asymmetric division via notch signaling in the developing neocortex. Neuron 63, 189-202 (2009).
41. Chenn, A. & Walsh, C. A. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science 297, 365-369 (2002).
42. Machold, R. et al. Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron 39, 937-950 (2003).
43. Iwata, T. & Hevner, R. F. Fibroblast growth factor signaling in development of the cerebral cortex. Dev. Growth Differ. 51, 299-323 (2009).
44. Yoon, K. & Gaiano, N. Notch signaling in the mammalian central nervous system: insights from mouse mutants. Nature Neurosci. 8, 709-715 (2005).
45. Jiang, J. Regulation of Hh/Gli signaling by dual ubiquitin pathways. Cell Cycle 5, 2457-2463 (2006).
46. Foltz, D. R., Santiago, M. C., Berechid, B. E. & Nye, J. S. Glycogen synthase kinase-3β modulates notch signaling and stability. Curr. Biol. 12, 1006-1011 (2002).
47. Espinosa, L., Ingles-Esteve, J., Aguilera, C. & Bigas, A. Phosphorylation by glycogen synthase kinase-3 β down-regulates Notch activity, a link for Notch and Wnt pathways. J. Biol. Chem. 278, 32227-32235 (2003).
48. Gregory, M. A., Qi, Y. & Hann, S. R. Phosphorylation by glycogen synthase kinase-3 controls c-myc proteolysis and subnuclear localization. J. Biol. Chem. 278, 51606-51612 (2003).
49. Sayas, C. L., Avila, J. & Wandosell, F. Glycogen synthase kinase-3 is activated in neuronal cells by α12 and α13 by Rho-independent and Rho-dependent mechanisms. J. Neurosci. 22, 6863-6875 (2002).
50. Kingsbury, M. A., Rehen, S. K., Contos, J. J., Higgins, C. M. & Chun, J. Non-proliferative effects of lysophosphatidic acid enhance cortical growth and folding. Nature Neurosci. 6, 1292-1299 (2003).
51. Gauthier-Fisher, A. et al. Lfc and Tctex-1 regulate the genesis of neurons from cortical precursor cells. Nature Neurosci. 12, 735-744 (2009).
52. Siegenthaler, J. A. et al. Retinoic acid from the meninges regulates cortical neuron generation. Cell 139, 597-609 (2009).
53. Benkoussa, M., Brand, C., Delmotte, M. H., Formstecher, P. & Lefebvre, P. Retinoic acid receptors inhibit AP1 activation by regulating extracellular signal-regulated kinase and CBP recruitment to an AP1-responsive promoter. Mol. Cell. Biol. 22, 4522-4534 (2002).
54. Spittaels, K. et al. Neonatal neuronal overexpression of glycogen synthase kinase-3 β reduces brain size in transgenic mice. Neuroscience 11 3, 797-808 (2002).
55. Kim, N. G., Xu, C. & Gumbiner, B. M. Identification of targets of the Wnt pathway destruction complex in addition to β-catenin. Proc. Natl Acad. Sci. USA 106, 5165-5170 (2009).
56. Xu, C., Kim, N. G. & Gumbiner, B. M. Regulation of protein stability by GSK3 mediated phosphorylation. Cell Cycle 8, 4032-4039 (2009).
57. Fuentealba, L. C., Eivers, E., Geissert, D., Taelman, V. & De Robertis, E. M. Asymmetric mitosis: unequal segregation of proteins destined for degradation. Proc. Natl Acad. Sci. USA 105, 7732-7737 (2008).
58. Wang, X. et al. Asymmetric centrosome inheritance maintains neural progenitors in the neocortex. Nature 461, 947-955 (2009).
59. Hong, Y. R. et al. Cloning and characterization of a novel human ninein protein that interacts with the glycogen synthase kinase 3β. Biochim. Biophys. Acta 1492, 513-516 (2000).
60. Hong, Y. R., Chen, C. H., Chuo, M. H., Liou, S. Y. & Howng, S. L. Genomic organization and molecular characterization of the human ninein gene. Biochem. Biophys. Res. Commun. 279, 989-995 (2000).
61. Howng, S. L. et al. A novel ninein-interaction protein, CGI-99, blocks ninein phosphorylation by GSK3β and is highly expressed in brain tumors. FEBS Lett. 566, 162-168 (2004).
62. Didier, C., Merdes, A., Gairin, J. E. & Jabrane-Ferrat, N. Inhibition of proteasome activity impairs centrosome-dependent microtubule nucleation and organization. Mol. Biol. Cell 19, 1220-1229 (2008).
63. Mimori-Kiyosue, Y. & Tsukita, S. Where is APC going? J. Cell Biol. 154, 1105-1109 (2001).
64. Yamashita, Y. M., Jones, D. L. & Fuller, M. T. Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome. Science 301, 1547-1550 (2003).
65. Yokota, Y. et al. The adenomatous polyposis coli protein is an essential regulator of radial glial polarity and construction of the cerebral cortex. Neuron 61, 42-56 (2009).
66. Asada, N., Sanada, K. & Fukada, Y. LKB1 regulates neuronal migration and neuronal differentiation in the developing neocortex through centrosomal positioning. J. Neurosci. 27, 11769-11775 (2007).
67. Barnes, A. P. et al. LKB1 and SAD kinases define a pathway required for the polarization of cortical neurons. Cell 129, 549-563 (2007).
68. Chen, Y. M. et al. Microtubule affinity-regulating kinase 2 functions downstream of the PAR-3/PAR-6/atypical PKC complex in regulating hippocampal neuronal polarity. Proc. Natl Acad. Sci. USA 103, 8534-8539 (2006).
69. Jiang, H., Guo, W., Liang, X. & Rao, Y. Both the establishment and the maintenance of neuronal polarity require active mechanisms: critical roles of GSK-3β and its upstream regulators. Cell 120, 123-135 (2005).
70. Kishi, M., Pan, Y. A., Crump, J. G. & Sanes, J. R. Mammalian SAD kinases are required for neuronal polarization. Science 307, 929-932 (2005).
71. Schwamborn, J. C. & Puschel, A. W. The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity. Nature Neurosci. 7, 923-929 (2004).
72. Shelly, M., Cancedda, L., Heilshorn, S., Sumbre, G. & Poo, M. M. LKB1/STRAD promotes axon initiation during neuronal polarization. Cell 129, 565-577 (2007).
73. Shi, S. H., Cheng, T., Jan, L. Y. & Jan, Y. N. APC and GSK-3β are involved in mPar3 targeting to the nascent axon and establishment of neuronal polarity. Curr. Biol. 14, 2025-2032 (2004).
74. Shi, S. H., Jan, L. Y. & Jan, Y. N. Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity. Cell 11 2, 63-75 (2003).
75. Yoshimura, T. et al. Ras regulates neuronal polarity via the PI3-kinase/Akt/GSK-3β/CRMP-2 pathway. Biochem. Biophys. Res. Commun. 340, 62-68 (2006).
76. Yoshimura, T. et al. GSK-3β regulates phosphorylation of CRMP-2 and neuronal polarity. Cell 120, 137-149 (2005). (Pubitemid 40094609)
77. Linding, R. et al. Systematic discovery of in vivo phosphorylation networks. Cell 129, 1415-1426 (2007).
78. Challacombe, J. F., Snow, D. M. & Letourneau, P. C. Dynamic microtubule ends are required for growth cone turning to avoid an inhibitory guidance cue. J. Neurosci. 17, 3085-3095 (1997).
79. Geraldo, S., Khanzada, U. K., Parsons, M., Chilton, J. K. & Gordon-Weeks, P. R. Targeting of the F-actin-binding protein drebrin by the microtubule plus-tip protein EB3 is required for neuritogenesis. Nature Cell Biol. 10, 1181-1189 (2008).
80. Tanaka, E., Ho, T. & Kirschner, M. W. The role of microtubule dynamics in growth cone motility and axonal growth. J. Cell Biol. 128, 139-155 (1995).
81. Bradke, F. & Dotti, C. G. The role of local actin instability in axon formation. Science 283, 1931-1934 (1999).
82. Da Silva, J. S., Hasegawa, T., Miyagi, T., Dotti, C. G. & Abad-Rodriguez, J. Asymmetric membrane ganglioside sialidase activity specifies axonal fate. Nature Neurosci. 8, 606-615 (2005).
83. Witte, H., Neukirchen, D. & Bradke, F. Microtubule stabilization specifies initial neuronal polarization. J. Cell Biol. 180, 619-632 (2008).
84. Conde, C. & Caceres, A. Microtubule assembly, organization and dynamics in axons and dendrites. Nature Rev. Neurosci. 10, 319-332 (2009).
85. Fukata, Y. et al. CRMP-2 binds to tubulin heterodimers to promote microtubule assembly. Nature Cell Biol. 4, 583-591 (2002).
86. Inagaki, N. et al. CRMP-2 induces axons in cultured hippocampal neurons. Nature Neurosci. 4, 781-782 (2001).
87. Votin, V., Nelson, W. J. & Barth, A. I. Neurite outgrowth involves adenomatous polyposis coli protein and β-catenin. J. Cell Sci. 11 8, 5699-5708 (2005).
88. Zumbrunn, J., Kinoshita, K., Hyman, A. A. & Nathke, I. S. Binding of the adenomatous polyposis coli protein to microtubules increases microtubule stability and is regulated by GSK3 β phosphorylation. Curr. Biol. 11, 44-49 (2001).
89. Stoothoff, W. H. & Johnson, G. V. Ta u phosphorylation: physiological and pathological consequences. Biochim. Biophys. Acta 1739, 280-297 (2005).
90. Trivedi, N., Marsh, P., Goold, R. G., Wood-Kaczmar, A. & Gordon-Weeks, P. R. Glycogen synthase kinase-3β phosphorylation of MAP1B at Ser1260 and Thr1265 is spatially restricted to growing axons. J. Cell Sci. 11 8, 993-1005 (2005).
91. Takei, Y., Teng, J., Harada, A. & Hirokawa, N. Defects in axonal elongation and neuronal migration in mice with disrupted tau and map1b genes. J. Cell Biol. 150, 989-1000 (2000).
92. Gartner, A., Huang, X. & Hall, A. Neuronal polarity is regulated by glycogen synthase kinase-3 (GSK-3β) independently of Akt/PKB serine phosphorylation. J. Cell Sci. 11 9, 3927-3934 (2006).
93. Nishimura, T. et al. PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1. Nature Cell Biol. 7, 270-277 (2005).
94. Zhang, X. et al. Dishevelled promotes axon differentiation by regulating atypical protein kinase C. Nature Cell Biol. 9, 743-754 (2007).
95. Nishimura, I., Yang, Y. & Lu, B. PAR-1 kinase plays an initiator role in a temporally ordered phosphorylation process that confers tau toxicity in Drosophila. Cell 11 6, 671-682 (2004).
96. Kosuga, S. et al. GSK-3β directly phosphorylates and activates MARK2/PAR-1. J. Biol. Chem. 280, 42715-42722 (2005).
97. Timm, T. et al. Glycogen synthase kinase (GSK) 3β directly phosphorylates Serine 212 in the regulatory loop and inhibits microtubule affinity-regulating kinase (MARK) 2. J. Biol. Chem. 283, 18873-18882 (2008).
98. Wildonger, J., Jan, L. Y. & Jan, Y. N. The Tsc1-Tsc2 complex influences neuronal polarity by modulating TORC1 activity and SAD levels. Genes Dev. 22, 2447-2453 (2008).
99. Ossipova, O., Bardeesy, N., DePinho, R. A. & Green, J. B. LKB1 (XEEK1) regulates Wnt signalling in vertebrate development. Nature Cell Biol. 5, 889-894 (2003).
100. Crino, P. B., Nathanson, K. L. & Henske, E. P. The tuberous sclerosis complex. N. Engl. J. Med. 355, 1345-1356 (2006).
101. Wullschleger, S., Loewith, R. & Hall, M. N. TOR signaling in growth and metabolism. Cell 124, 471-484 (2006).
102. Polak, P. & Hall, M. N. mTOR and the control of whole body metabolism. Curr. Opin. Cell Biol. 21, 209-218 (2009).
103. Plas, D. R. & Thomas, G. Tubers and tumors: rapamycin therapy for benign and malignant tumors. Curr. Opin. Cell Biol. 21, 230-236 (2009).
104. Guertin, D. A. & Sabatini, D. M. Defining the role of mTOR in cancer. Cancer Cell 12, 9-22 (2007).
105. Choi, Y. J. et al. Tuberous sclerosis complex proteins control axon formation. Genes Dev. 22, 2485-2495 (2008).
106. Morita, T. & Sobue, K. Specification of neuronal polarity regulated by local translation of CRMP2 and Tau via the mTOR-p70S76K pathway. J. Biol. Chem. 284, 27734-27745 (2009).
107. Inoki, K. et al. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell 126, 955-968 (2006).
108. Yan, D., Guo, L. & Wang, Y. Requirement of dendritic Akt degradation by the ubiquitin-proteasome system for neuronal polarity. J. Cell Biol. 174, 415-424 (2006).
109. Zhou, F. Q. & Snider, W. D. Intracellular control of developmental and regenerative axon growth. Phil. Trans. R. Soc. Lond. B 361, 1575-1592 (2006).
110. Zhou, F. Q., Zhou, J., Dedhar, S., Wu, Y. H. & Snider, W. D. NGF-induced axon growth is mediated by localized inactivation of GSK-3β and functions of the microtubule plus end binding protein APC. Neuron 42, 897-912 (2004).
111. Frame, S., Cohen, P. & Biondi, R. M. A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation. Mol. Cell 7, 1321-1327 (2001).
112. Dent, E. W. & Gertler, F. B. Cytoskeletal dynamics and transport in growth cone motility and axon guidance. Neuron 40, 209-227 (2003).
113. Lu, W., Yamamoto, V., Ortega, B. & Baltimore, D. Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth. Cell 11 9, 97-108 (2004).
114. Lonze, B. E., Riccio, A., Cohen, S. & Ginty, D. D. Apoptosis, axonal growth defects, and degeneration of peripheral neurons in mice lacking CREB. Neuron 34, 371-385 (2002).
115. Vo, N. & Goodman, R. H. CREB-binding protein and p300 in transcriptional regulation. J. Biol. Chem. 276, 13505-13508 (2001).
116. Riccio, A. et al. A nitric oxide signaling pathway controls CREB-mediated gene expression in neurons. Mol. Cell 21, 283-294 (2006).
117. Graef, I. A. et al. Neurotrophins and netrins require calcineurin/NFAT signaling to stimulate outgrowth of embryonic axons. Cell 11 3, 657-670 (2003).
118. Mi, K., Dolan, P. J. & Johnson, G. V. The low density lipoprotein receptor-related protein 6 interacts with glycogen synthase kinase 3 and attenuates activity. J. Biol. Chem. 281, 4787-4794 (2006).
119. Dajani, R. et al. Crystal structure of glycogen synthase kinase 3 β: structural basis for phosphate-primed substrate specificity and autoinhibition. Cell 10 5, 721-732 (2001).
120. Hartigan, J. A., Xiong, W. C. & Johnson, G. V. Glycogen synthase kinase 3β is tyrosine phosphorylated by PYK2. Biochem. Biophys. Res. Commun. 284, 485-489 (2001).
121. Cole, A., Frame, S. & Cohen, P. Further evidence that the tyrosine phosphorylation of glycogen synthase kinase-3 (GSK3) in mammalian cells is an autophosphorylation event. Biochem. J. 377, 249-255 (2004).
122. Liu, C. et al. Control of β-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108, 837-847 (2002).
123. Wei, W., Jin, J., Schlisio, S., Harper, J. W. & Kaelin, W. G. Jr. The v-Jun point mutation allows c-Jun to escape GSK3-dependent recognition and destruction by the Fbw7 ubiquitin ligase. Cancer Cell 8, 25-33 (2005).
124. Diehl, J. A., Cheng, M., Roussel, M. F. & Sherr, C. J. Glycogen synthase kinase-3β regulates cyclin D1 proteolysis and subcellular localization. Genes Dev. 12, 3499-3511 (1998).
125. Welcker, M. et al. Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation. Mol. Cell 12, 381-392 (2003).
126. Kumar, P. et al. GSK3β phosphorylation modulates CLASP-microtubule association and lamella microtubule attachment. J. Cell Biol. 184, 895-908 (2009).
127. Goold, R. G., Owen, R. & Gordon-Weeks, P. R. Glycogen synthase kinase 3β phosphorylation of microtubule-associated protein 1B regulates the stability of microtubules in growth cones. J. Cell Sci. 11 2, 3373-3384 (1999).
128. Lee, H. et al. The microtubule plus end tracking protein Orbit/MAST/CLASP acts downstream of the tyrosine kinase Abl in mediating axon guidance. Neuron 42, 913-926 (2004).
129. van Diepen, M. T. et al. MyosinV controls PTEN function and neuronal cell size. Nature Cell Biol. 11, 1191-1196 (2009).
130. Morfini, G., Szebenyi, G., Elluru, R., Ratner, N. & Brady, S. T. Glycogen synthase kinase 3 phosphorylates kinesin light chains and negatively regulates kinesin-based motility. EMBO J. 21, 281-293 (2002).
131. Welsh, G. I., Miller, C. M., Loughlin, A. J., Price, N. T. & Proud, C. G. Regulation of eukaryotic initiation factor eIF2B: glycogen synthase kinase-3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin. FEBS Lett. 421, 125-130 (1998).