Inactivation of glycogen synthase kinase 3β (GSK3β) and the resulting stabilization of free β-catenin are critical steps in the activation of Wnt target genes. While Akt regulates GSK3α/β in the phosphatidylinositide 3-OH kinase signaling pathway, its role in Wnt signaling is unknown. Here we report that expression of Wnt or Dishevelled (Dvl) increased Akt activity. Activated Akt bound to the Axin-GSK3β complex in the presence of Dvl, phosphorylated GSK3β and increased free β-catenin levels. Furthermore, in Wnt-overexpressing PC12 cells, dominant-negative Akt decreased free β-catenin and derepressed nerve growth factor-induced differentiation. Therefore, Akt acts in association with Dvl as an important regulator of the Wnt signaling pathway.
CITATION STYLE
Fukumoto, S., Hsieh, C. M., Maemura, K., Layne, M. D., Yet, S. F., Lee, K. H., … Lee, M. E. (2001). Akt Participation in the Wnt Signaling Pathway through Dishevelled. Journal of Biological Chemistry, 276(20), 17479–17483. https://doi.org/10.1074/jbc.C000880200
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