Original Research Article
Phosphorylation of AKT/PKB by CK2 is necessary for the AKT-dependent up-regulation of β-catenin transcriptional activity
Version of Record online: 19 APR 2011
Copyright © 2010 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 226, Issue 7, pages 1953–1959, July 2011
How to Cite
Ponce, D. P., Maturana, J. L., Cabello, P., Yefi, R., Niechi, I., Silva, E., Armisen, R., Galindo, M., Antonelli, M. and Tapia, J. C. (2011), Phosphorylation of AKT/PKB by CK2 is necessary for the AKT-dependent up-regulation of β-catenin transcriptional activity. J. Cell. Physiol., 226: 1953–1959. doi: 10.1002/jcp.22527
- Issue online: 19 APR 2011
- Version of Record online: 19 APR 2011
- Accepted manuscript online: 15 NOV 2010 12:00AM EST
- Manuscript Accepted: 28 OCT 2010
- Manuscript Received: 26 OCT 2010
- Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT). Grant Numbers: 15010006, 1095234, 11070116
β-Catenin is a key protein in the canonical Wnt signaling pathway and in many cancers alterations in transcriptional activity of its components are observed. This pathway is up-regulated by the protein kinase CK2, but the underlying mechanism of this change is unknown. It has been demonstrated that CK2 hyperactivates AKT/PKB by phosphorylation at Ser129, and AKT phosphorylates β-catenin at Ser552, which in turn, promotes its nuclear localization and transcriptional activity. However, the consequences of CK2-dependent hyperactivation of AKT on β-catenin activity and cell viability have not been evaluated. We assessed this regulatory process by manipulating the activity of CK2 and AKT through overexpression of wild-type, constitutively active and dominant negative forms of these proteins as well as analyzing β-catenin-dependent transcriptional activity, survivin expression and viability in HEK-293T cells. We observed that CK2α overexpression up-regulated the β-catenin transcriptional activity, which correlated to an increased nuclear localization of β-catenin as well as survivin expression. Importantly, these effects were strongly reversed when an AKT-S129A mutant was co-expressed in the same cells, followed by a significant decrease in cell viability but no changes in β-catenin stability. Taken together, the data suggest that the CK2α-dependent up-regulation of β-catenin activity requires phosphorylation of AKT in human embryonic kidney cells. J. Cell. Physiol. 226: 1953–1959, 2011. © 2010 Wiley-Liss, Inc.