NLK positively regulates Wnt/β-catenin signalling by phosphorylating LEF1 in neural progenitor cells

Satoshi Ota, Shizuka Ishitani, Nobuyuki Shimizu, Kunihiro Matsumoto, Motoyuki Itoh, Tohru Ishitani

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1904-1915
Number of pages12
JournalEMBO Journal
Volume31
Issue number8
DOIs
Publication statusPublished - Apr 18 2012

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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