NLK positively regulates Wnt/β‐catenin signalling by phosphorylating LEF1 in neural progenitor cells
Open accessAbstract
Nemo-like kinase (NLK/Nlk) is an evolutionarily conserved protein kinase involved in Wnt/β-catenin signalling. However, the roles of NLK in Wnt/β-catenin signalling in vertebrates remain unclear. Here, we show that inhibition of Nlk2 function in zebrafish results in decreased Lymphoid enhancer factor-1 (Lef1)-mediated gene expression and cell proliferation in the presumptive midbrain, resulting in a reduction of midbrain tectum size. These defects are related to phosphorylation of Lef1 by Nlk2. Thus, Nlk2 is essential for the phosphorylation and activation of Lef1 transcriptional activity in neural progenitor cells (NPCs). In NPC-like mammalian cells, NLK is also required for the phosphorylation and activation of LEF1 transcriptional activity. Phosphorylation of LEF1 induces its dissociation from histone deacetylase, thereby allowing transcription activation. Furthermore, we demonstrate that NLK functions downstream of Dishevelled (Dvl) in the Wnt/β-catenin signalling pathway. Our findings reveal a novel role of NLK in the activation of the Wnt/β-catenin signalling pathway.
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In zebrafish, NLK signalling contributed to midbrain tectum development by promoting neural progenitor cell proliferation.
“In zebrafish, NLK signalling contributed to midbrain tectum development by promoting neural progenitor cell proliferation [21].”
From Nemo-Like Kinase in Development and Diseases: Insights from Mouse Studies (2020) · cites this paper as [21]
Activation of NLK-induced phosphorylation of LEF1 and dissociation from HDAC1 facilitated LEF1-mediated target gene transcription.
“Furthermore, it was shown that activation of NLK-induced phosphorylation of LEF1 and dissociation from histone deacetylase 1 (HDAC1) facilitated LEF1-mediated target gene transcription [21].”
From Nemo-Like Kinase in Development and Diseases: Insights from Mouse Studies (2020) · cites this paper as [21]
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References 64 · Cited by 82
- Authors
- Ota, S., Ishitani, S., Shimizu, N., Matsumoto, K., Itoh, M., & Ishitani, T.
- Affiliations
- Kyushu University (JP)
- Nagoya University (JP)
- Nagoya University Institute for Advanced Research (JP)
- Corresponding author
- Ishitani, Tohru
- Venue
- The EMBO Journal
- Published
- 2012-02-28
- Volume
- 31
- Issue
- 8
- Pages
- 1904-1915
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC3343332
- OpenAlex
- W1851499913
- Cited by
- 82
- References
- 64
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 6 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 8 · 2017: 6 · 2016: 6 · 2015: 7 · 2014: 7 · 2013: 13 · 2012: 3
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Brain Science Foundation
- Astellas Pharma
- Astellas Foundation for Research on Metabolic Disorders
- Research Foundation for Opto-Science and Technology
- Japan Society for the Promotion of Science (21247031, 22689008)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- Nemo-like kinase, Wnt/β-catenin signaling, neural progenitor cells, histone deacetylase, Dishevelled, transcriptional activation, zebrafish, cell proliferation
- MeSH terms
- Animals, Brain, Cells, Cultured, Humans, Phosphorylation, Stem Cells, Transcription Factors, Zebrafish, Signal Transduction, Mitogen-Activated Protein Kinases, Zebrafish Proteins, Wnt1 Protein, beta Catenin
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