Phosphorylation of AKT/PKB by CK2 Is Necessary for the AKT-Dependent Up-Regulation of β-Catenin Transcriptional Activity

beta-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 beta-catenin at Ser552, which in turn, promotes its nuclear localization and transcriptional activity. However, the consequences of CK2-dependent hyperactivation of AKT on beta-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 beta-catenin-dependent transcriptional activity, survivin expression and viability in HEK-293T cells. We observed that CK2 alpha overexpression up-regulated the beta-catenin transcriptional activity, which correlated to an increased nuclear localization of beta-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 beta-catenin stability. Taken together, the data suggest that the CK2 alpha-dependent up-regulation of beta-catenin activity requires phosphorylation of AKT in human embryonic kidney cells. J. Cell. Physiol. 226: 1953-1959, 2011. (C) 2010 Wiley-Liss, Inc.