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GSK3? exhibits ?-catenin and tau directed kinase activities that are modulated by Wnt

GSK3? exhibits ?-catenin and tau directed kinase activities that are modulated by Wnt
GSK3? exhibits ?-catenin and tau directed kinase activities that are modulated by Wnt
In the presence of a Wnt signal ?-catenin is spared from proteasomal degradation through a complex mechanism involving GSK3?, resulting in the transcription of Wnt target genes. In this study we have explored whether GSK3?, a related isoform, can also regulate nuclear ?-catenin levels and whether this and the tau-directed kinase activity of GSK3? are modulated by Wnt. GSK3? or GSK3? and their substrates, ?-catenin and tau, were transiently expressed in mammalian cells. Immunoblotting revealed that GSK3? reduces nuclear levels of ?-catenin, whilst reporter gene assays demonstrated that GSK3? inhibits ?-catenin-directed Tcf/Lef-dependent transcription. Moreover, activation of the Wnt pathway was found to attenuate both the ?-catenin- and the tau-directed kinase activities of GSK3? and GSK3?. By immunoprecipitation we also found that axin-1, the ?-catenin destruction complex scaffold protein, binds GSK3?. In the light of these findings GSK3? warrants further investigation regarding its involvement in Wnt signalling and tauopathies such as Alzheimer's disease.
alzheimer's, cull culture, cell signalling, diabetes, transcription
0953-816X
3387-3392
Asuni, Ayodeji A.
b1412b1b-9794-4705-aada-aed5d3da038f
Hooper, Claudie
7793fea9-f2bf-4aff-b788-7e077434ba95
Reynolds, C. Hugh
d2e27e82-31f3-4b9f-9a9e-cbb8515d88e4
Lovestone, Simon
8c74cdb9-c6cc-4f60-8ad4-beaf5b526040
Anderton, Brian H.
33184c75-df57-402f-ac03-abd14f51eb66
Killick, Richard
eefdd3bc-53d7-4ebb-82ff-e20d02a53d53
Asuni, Ayodeji A.
b1412b1b-9794-4705-aada-aed5d3da038f
Hooper, Claudie
7793fea9-f2bf-4aff-b788-7e077434ba95
Reynolds, C. Hugh
d2e27e82-31f3-4b9f-9a9e-cbb8515d88e4
Lovestone, Simon
8c74cdb9-c6cc-4f60-8ad4-beaf5b526040
Anderton, Brian H.
33184c75-df57-402f-ac03-abd14f51eb66
Killick, Richard
eefdd3bc-53d7-4ebb-82ff-e20d02a53d53

Asuni, Ayodeji A., Hooper, Claudie, Reynolds, C. Hugh, Lovestone, Simon, Anderton, Brian H. and Killick, Richard (2006) GSK3? exhibits ?-catenin and tau directed kinase activities that are modulated by Wnt. European Journal of Neuroscience, 24 (12), 3387-3392. (doi:10.1111/j.1460-9568.2006.05243.x).

Record type: Article

Abstract

In the presence of a Wnt signal ?-catenin is spared from proteasomal degradation through a complex mechanism involving GSK3?, resulting in the transcription of Wnt target genes. In this study we have explored whether GSK3?, a related isoform, can also regulate nuclear ?-catenin levels and whether this and the tau-directed kinase activity of GSK3? are modulated by Wnt. GSK3? or GSK3? and their substrates, ?-catenin and tau, were transiently expressed in mammalian cells. Immunoblotting revealed that GSK3? reduces nuclear levels of ?-catenin, whilst reporter gene assays demonstrated that GSK3? inhibits ?-catenin-directed Tcf/Lef-dependent transcription. Moreover, activation of the Wnt pathway was found to attenuate both the ?-catenin- and the tau-directed kinase activities of GSK3? and GSK3?. By immunoprecipitation we also found that axin-1, the ?-catenin destruction complex scaffold protein, binds GSK3?. In the light of these findings GSK3? warrants further investigation regarding its involvement in Wnt signalling and tauopathies such as Alzheimer's disease.

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Published date: December 2006
Keywords: alzheimer's, cull culture, cell signalling, diabetes, transcription
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 345520
URI: http://eprints.soton.ac.uk/id/eprint/345520
ISSN: 0953-816X
PURE UUID: f16f0041-668a-4789-bd0f-7ab95b1b4238

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Date deposited: 12 Feb 2013 15:18
Last modified: 16 Jul 2019 21:49

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Contributors

Author: Ayodeji A. Asuni
Author: Claudie Hooper
Author: C. Hugh Reynolds
Author: Simon Lovestone
Author: Brian H. Anderton
Author: Richard Killick

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