GSK3α exhibits β-catenin and tau directed kinase activities that are modulated by Wnt
| Autor: | Simon Lovestone, Claudie Hooper, C. Hugh Reynolds, Richard Killick, Brian H. Anderton, Ayodeji A. Asuni |
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| Rok vydání: | 2006 |
| Předmět: |
Gene isoform
Scaffold protein Beta-catenin Blotting Western tau Proteins Transfection Glycogen Synthase Kinase 3 Axin Protein Cricetinae Animals Humans Immunoprecipitation Kinase activity Luciferases GSK3B Phylogeny beta Catenin Cell Line Transformed Glycogen Synthase Kinase 3 beta biology Kinase General Neuroscience Wnt signaling pathway LRP6 Molecular biology Cell biology Repressor Proteins Wnt Proteins Gene Expression Regulation biology.protein Subcellular Fractions |
| Zdroj: | European Journal of Neuroscience. 24:3387-3392 |
| ISSN: | 1460-9568 0953-816X |
| Popis: | In the presence of a Wnt signal beta-catenin is spared from proteasomal degradation through a complex mechanism involving GSK3beta, resulting in the transcription of Wnt target genes. In this study we have explored whether GSK3alpha, a related isoform, can also regulate nuclear beta-catenin levels and whether this and the tau-directed kinase activity of GSK3alpha are modulated by Wnt. GSK3alpha or GSK3beta and their substrates, beta-catenin and tau, were transiently expressed in mammalian cells. Immunoblotting revealed that GSK3alpha reduces nuclear levels of beta-catenin, whilst reporter gene assays demonstrated that GSK3alpha inhibits beta-catenin-directed Tcf/Lef-dependent transcription. Moreover, activation of the Wnt pathway was found to attenuate both the beta-catenin- and the tau-directed kinase activities of GSK3alpha and GSK3beta. By immunoprecipitation we also found that axin-1, the beta-catenin destruction complex scaffold protein, binds GSK3alpha. In the light of these findings GSK3alpha warrants further investigation regarding its involvement in Wnt signalling and tauopathies such as Alzheimer's disease. |
| Databáze: | OpenAIRE |
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