Nemo-like kinase is involved in NGF-induced neurite outgrowth via phosphorylating MAP1B and paxillin

Tohru Ishitani, Shizuka Ishitani, Kunihiro Matsumoto, Motoyuki Itoh

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Nerve growth factor (NGF) promotes neurite outgrowth through regulating cytoskeletal organization and cell adhesion. These activities are modulated by protein phosphorylation. Nemo-like kinase (NLK) is an evolutionarily conserved MAP kinase-like kinase that phosphorylates several transcription factors. Although NLK is known to be expressed at relatively high levels in the nervous system, its function is not well understood. We found that NGF promotes the translocation of NLK to PC12 cells' leading edges, and triggers NLK kinase activity in them. Activated NLK directly phosphorylates microtubule-associated protein-1B (MAP1B) and the focal adhesion adaptor protein, paxillin. Knockdown of NLK attenuates the phosphorylation of both paxillin and MAP1B and inhibits both the NGF-induced re-distribution of F-actin and neurite outgrowth. We also discovered that NLK is a LiCl-sensitive kinase. LiCl is known to block NGF-induced neurite outgrowth and the phosphorylation of MAP1B and paxillin in PC12 cells. Therefore, the effects of LiCl are mediated in part by blocking NLK activity. These results suggest that NLK controls the dynamics of the cytoskeleton downstream of NGF signaling.

Original languageEnglish
Pages (from-to)1104-1118
Number of pages15
JournalJournal of Neurochemistry
Volume111
Issue number5
DOIs
Publication statusPublished - Dec 1 2009

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Paxillin
Nerve Growth Factor
Phosphotransferases
Phosphorylation
PC12 Cells
microtubule-associated protein 1B
Neuronal Outgrowth
Focal Adhesions
Mitogen-Activated Protein Kinase Kinases
Cytoskeleton
Cell Adhesion
Cell adhesion
Nervous System
Neurology
Actins
Proteins
Transcription Factors

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Nemo-like kinase is involved in NGF-induced neurite outgrowth via phosphorylating MAP1B and paxillin. / Ishitani, Tohru; Ishitani, Shizuka; Matsumoto, Kunihiro; Itoh, Motoyuki.

In: Journal of Neurochemistry, Vol. 111, No. 5, 01.12.2009, p. 1104-1118.

Research output: Contribution to journalArticle

Ishitani, Tohru ; Ishitani, Shizuka ; Matsumoto, Kunihiro ; Itoh, Motoyuki. / Nemo-like kinase is involved in NGF-induced neurite outgrowth via phosphorylating MAP1B and paxillin. In: Journal of Neurochemistry. 2009 ; Vol. 111, No. 5. pp. 1104-1118.
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