SpringerProtocols: Abstract: 5. Inhibition of Glycogen Synthase Kinase-3

5. Inhibition of Glycogen Synthase Kinase-3

By: Andrei V. Ougolkov³, Daniel D. Billadeau³

Abstract

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There are two homologous forms of glycogen synthase kinase (GSK)-3, GSK-3α and GSK-3β, which play overlapping roles in the regulation of Wnt, Hedgehog, and insulin pathways, as well as the activation of nuclear factor (NF)-kB-mediated gene transcription. These signaling pathways regulate gene transcription, cell cycle, apoptosis, inflammation, glucose metabolism, stem-cell renewal, and differentiation. More than 50 GSK-3 inhibitors representing a wide range of chemical structures have already been identified, and their utility in the treatment of type II diabetes mellitus, Alzheimer's disease, bipolar diseases, cancer, and other human pathologies is currently being investigated. Here, we discuss two methods of GSK-3 inhibition, which can be used to determine the involvement of GSK-3 in a cellular process of interest.

Affiliation(s): (3) Division of Oncology Research, Mayo Clinic College of Medicine, Rochester MN, USA

Book Title: Wnt Signaling: Pathway Methods and Mammalian Models

Series: Methods in Molecular Biology | Volume: 468 | Pub. Date: Jul-01-2008 | Page Range: 67-75 | DOI: 10.1007/978-1-59745-249-6_5

Subject: Protein Science

Key Words: Glycogen synthase kinase-3 - β-catenin - glycogen synthase

References

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1.	Plyte SE, Hughes K, Nikolakaki E, Pulverer BJ, Wood-gett JR. (1992) Glycogen synthase kinase-3: functions in oncogenesis and development. Biochim Biophys Acta. 1114, 147–162.

2.	Frame S, Cohen P. (2001) GSK3 takes centre stage more than 20 years after its discovery. Biochem J. 359, 1–16.

3.	Doble BW, Woodgett JR. (2003) GSK-3: tricks of the trade for a multi-tasking kinase. J Cell Sci. 116, 1175–1186.

4.	Cohen P, Frame S. (2001) The renaissance of GSK3. Nat Rev Mol Cell Biol. 2, 769–776.

5.	Cohen P, Goedert M. (2004) GSK3 inhibitors: development and therapeutic potential. Nat Rev Drug Discov. 3, 479–487.

6.	Ougolkov AV, Billadeau DD. (2006) Targeting GSK-3: a promising approach for cancer therapy? Future Oncol. 2, 91–100.

7.	Dugo L, Collin M, Thiemermann C. (2007) Glycogen synthase kinase 3beta as a target for the therapy of shock and inflammation. Shock. 27, 113–123.

8.	Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, Polakis P. (1996) Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science. 272, 1023–1026.

9.	Yamamoto H, Kishida S, Kishida M, Ikeda S, Takada S, Kikuchi A. (1999) Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3beta regulates its stability. J Biol Chem. 274, 10681–10684.

10.	Ding VW, Chen RH, McCormick F. (2000) Differential regulation of glycogen synthase kinase 3beta by insulin and Wnt signaling. J Biol Chem. 275, 32475–32481.

11.	Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O, Woodgett JR. (2000) Requirement for gly-cogen synthase kinase-3beta in cell survival and NF-kappaB activation. Nature. 406, 86–90.

12.	Meijer L, Flajolet M, Greengard P. (2004) Pharmacological inhibitors of glycogen synthase kinase 3. Trends Pharmacol Sci. 25, 471–480.

13.	Martinez A, Castro A, Dorronsoro I, Alonso M. (2002) Glycogen synthase kinase 3 (GSK-3) inhibitors as new promising drugs for diabetes, neurodegeneration, cancer, and inflammation. Med Res Rev. 22, 373–384.

14.	Alonso M, Martinez A. (2004) GSK-3 inhibitors: discoveries and developments. Curr Med Chem. 11, 755–763.

15.	Stambolic V, Ruel L, Woodgett JR. (1996) Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Curr Biol. 6, 1664–1668.

16.	Ryves WJ, Harwood AJ. (2001) Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. Biochem Biophys Res Commun. 280, 720–725.

17.	Mora A, Sabio G, Gonzalez-Polo RA, et al. (2001) Lithium inhibits caspase 3 activation and dephosphorylation of PKB and GSK3 induced by K+ deprivation in cerebellar granule cells. J Neurochem. 78, 199–206.

18.	Ilouz R, Kaidanovich O, Gurwitz D, Eldar-Finkelman H. (2002) Inhibition of glycogen synthase kinase-3beta by bivalent zinc ions: insight into the insulin-mimetic action of zinc. Biochem Biophys Res Commun. 295, 102–106.

19.	Leclerc S, Garnier M, Hoessel R, et al. (2001) Indirubins inhibit glycogen synthase kinase-3 beta and CDK5/p25, two protein kinases involved in abnormal tau phosphor ylation in Alzheimer's disease. A p r operty common to most cyclin-dependent kinase inhibitors? J Biol Chem. 276, 251–260.

20.	Leost M, Schultz C, Link A, et al. (2000) Paullones are potent inhibitors of glycogen syn-thase kinase-3beta and cyclin-dependent kinase 5/p25. Eur J Biochem. 267, 5983–5994.

21.	Smith DG, Buffet M, Fenwick AE, et al. (2001) 3-Anilino-4-arylmaleimides: potent and selective inhibitors of glycogen synthase kinase-3 (GSK-3). Bioorg Med Chem Lett. 11, 635–639.

22.	Cross DA, Culbert AA, Chalmers KA, Facci L, Skaper SD, Reith AD. (2001) Selective small-molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurones from death. J Neurochem. 77, 94–102.

23.	Bhat R, Xue Y, Berg S, et al. (2003) Structural insights and biological effects of glycogen syn-thase kinase 3-specific inhibitor AR-A014418. J Biol Chem. 278, 45937–45945.

24.	Martinez A, Alonso M, Castro A, Perez C, Moreno FJ. (2002) First non-ATP competitive glycogen synthase kinase 3 beta (GSK-beta) inhibitors: thiadiazolidinones (TDZD) as potential drugs for the treatment of Alzheimer's disease. J Med Chem. 45, 1292–1299.

25.	Ougolkov AV, Fernandez-Zapico ME, Savoy DN, Urrutia RA, Billadeau DD. (2005) Glycogen synthase kinase-3beta participates in nuclear factor kappaB-medi-ated gene transcription and cell survival in pancreatic cancer cells. Cancer Res. 65, 2076–2081.

26.	Zakaria S, Gomez TS, Savoy DN, et al. (2004) Differential regulation of TCR-mediated gene transcription by Vav family members. J Exp Med. 199, 429–434.

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