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.
Original language | English |
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Pages (from-to) | 16-25 |
Number of pages | 10 |
Journal | Proceedings of the Japan Academy Series B: Physical and Biological Sciences |
Volume | 83 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2007 |
Keywords
- Nemo-like kinase
- Neuroblastoma
- Osteosarcoma
- TCF
- Wnt signaling
- β-catenin
ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Physics and Astronomy(all)