Homodimerization of nemo-like kinase is essential for activation and nuclear localization

Shizuka Ishitani, Kenji Inaba, Kunihiro Matsumoto, Tohru Ishitani

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Nemo-like kinase (NLK) is an evolutionarily conserved protein kinase that phosphorylates several transcription factors. However, the molecular mechanisms that regulate NLK activity have been poorly understood. Here we show that homodimerization of NLK is required for its activation and nuclear localization. Biochemical analysis revealed that NLK is activated through intermolecular autophosphorylation of NLK dimers at Thr-286. Mutation of NLK at Cys-425, which corresponds to the defect in the Caenorhabditis elegans NLK homologue lit-1 , prevented NLK dimerization, rendering NLK defective in both nuclear localization and kinase activity. By contrast, the external addition of nerve growth factor, which has been previously identified as an NLK activator, induced dimerization and Thr-286 autophosphorylation of endogenous NLK proteins. In addition, both dimerization and Thr-286 phosphorylation of NLK were found to be essential for induction of neurite-like cellular processes by NLK. The present findings suggest that dimerization is an initial key event required for the functional activation of NLK.

Original languageEnglish
Pages (from-to)266-277
Number of pages12
JournalMolecular biology of the cell
Volume22
Issue number2
DOIs
Publication statusPublished - Jan 15 2011

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Phosphotransferases
Dimerization
Protein Kinases
Caenorhabditis elegans
Nerve Growth Factor
Neurites
Transcription Factors
Phosphorylation
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Homodimerization of nemo-like kinase is essential for activation and nuclear localization. / Ishitani, Shizuka; Inaba, Kenji; Matsumoto, Kunihiro; Ishitani, Tohru.

In: Molecular biology of the cell, Vol. 22, No. 2, 15.01.2011, p. 266-277.

Research output: Contribution to journalArticle

Ishitani, Shizuka ; Inaba, Kenji ; Matsumoto, Kunihiro ; Ishitani, Tohru. / Homodimerization of nemo-like kinase is essential for activation and nuclear localization. In: Molecular biology of the cell. 2011 ; Vol. 22, No. 2. pp. 266-277.
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