GSK3α exhibits β-catenin and tau directed kinase activities that are modulated by Wnt

• Published in: The European journal of neuroscience 2006-12, Vol.24 (12), p.3387-3392
• Main Authors: Asuni, Ayodeji A., Hooper, Claudie, Reynolds, C. Hugh, Lovestone, Simon, Anderton, Brian H., Killick, Richard
• Format: Article
• Language: English
• Subjects: Alzheimer's; cell culture; cell signalling; diabetes; transcription
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2006.05243.x

In the presence of a Wnt signal β‐catenin is spared from proteasomal degradation through a complex mechanism involving GSK3β, resulting in the transcription of Wnt target genes. In this study we have explored whether GSK3α, a related isoform, can also regulate nuclear β‐catenin levels and whether this and the tau‐directed kinase activity of GSK3α are modulated by Wnt. GSK3α or GSK3β and their substrates, β‐catenin and tau, were transiently expressed in mammalian cells. Immunoblotting revealed that GSK3α reduces nuclear levels of β‐catenin, whilst reporter gene assays demonstrated that GSK3α inhibits β‐catenin‐directed Tcf/Lef‐dependent transcription. Moreover, activation of the Wnt pathway was found to attenuate both the β‐catenin‐ and the tau‐directed kinase activities of GSK3α and GSK3β. By immunoprecipitation we also found that axin‐1, the β‐catenin destruction complex scaffold protein, binds GSK3α. In the light of these findings GSK3α warrants further investigation regarding its involvement in Wnt signalling and tauopathies such as Alzheimer's disease.