title: Mammalian Nemo-like kinase enhances β-catenin-TCF transcription activity in human osteosarcoma and neuroblastoma cells.
abstract: Nemo-like kinase (NLK) is an evolutionarily conserved serine/threonine kinase and has been considered to be a suppressor of Wnt signaling in mammalian cells. Our study, however, has raised the possibility that NLK also functions as a Wnt signaling activator. In human osteosarcoma and neuroblastoma cell lines, NLK specifically enhanced β-catenin-TCF complex transcription activity. The effect required kinase activity of NLK and co-expression of the β-catenin ΔN (constitutive active mutant of β-catenin). The nuclear localization of Lymphoid enhancer factor 1 (LEF1) and β-catenin ΔN was not altered by NLK overexpression regardless of its effect on β-catenin-TCF complex activity. Reporter analysis using LEF1 mutants at known NLK target sites indicated that NLK may have different activation targets for β-catenin-TCF complex. Mutations in the potential NLK phosphorylation sites in β-catenin did not change its transcription activity either. Our results suggest that NLK positively regulates Wnt/β-catenin signaling in a cell type dependent manner through an unidentified mechanism.
authors.affiliation: Cancer Transcriptome Project, National Cancer Center Research Institute, Tokyo, Japan .
authors.forename: Jun
authors.initials: J
authors.lastname: Yasuda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ichikawa
keywords: Nemo-like kinase; TCF; Wnt signaling; neuroblastoma; osteosarcoma; β-catenin
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