title: Phosphorylation of AKT/PKB by CK2 is necessary for the AKT-dependent up-regulation of β-catenin transcriptional activity.
abstract: 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.
authors.affiliation: Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Daniela P
authors.initials: DP
authors.lastname: Ponce
authors.forename: Jose L
authors.initials: JL
authors.lastname: Maturana
authors.forename: Pablo
authors.initials: P
authors.lastname: Cabello
authors.forename: Roger
authors.initials: R
authors.lastname: Yefi
authors.forename: Ignacio
authors.initials: I
authors.lastname: Niechi
authors.forename: Eduardo
authors.initials: E
authors.lastname: Silva
authors.forename: Ricardo
authors.initials: R
authors.lastname: Armisen
authors.forename: Mario
authors.initials: M
authors.lastname: Galindo
authors.forename: Marcelo
authors.initials: M
authors.lastname: Antonelli
authors.forename: Julio C
authors.initials: JC
authors.lastname: Tapia
mesh_terms: D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival; D057809:HEK293 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012694:Serine; D000077022:Survivin; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C107489:BIRC5 protein, human; C495270:CTNNB1 protein, human; D051034:Inhibitor of Apoptosis Proteins; D011993:Recombinant Fusion Proteins; D000077022:Survivin; D051176:beta Catenin; D012694:Serine; D047390:Casein Kinase II; D051057:Proto-Oncogene Proteins c-akt