Phosphorylation of AKT/PKB by CK2 is necessary for the AKT-dependent up-regulation of β-catenin transcriptional activity
✍ Scribed by Daniela P. Ponce; Jose L. Maturana; Pablo Cabello; Roger Yefi; Ignacio Niechi; Eduardo Silva; Ricardo Armisen; Mario Galindo; Marcelo Antonelli; Julio C. Tapia
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 336 KB
- Volume
- 226
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
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.