Nucleolar Nek11 is a novel target of Nek2A in G1/S-arrested cells

Kohji Noguchi, Hidesuke Fukazawa, Yuko Murakami, Yoshimasa Uehara

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

We previously reported that Nek11, a member of the NIMA (never-in-mitosis A) family of kinases, is activated in G1/S-arrested cells. We provide herein several lines of evidence for a novel interaction between Nek11 and Nek2A. Both Nek11 and Nek2A, but not Nek2B, were detected at nucleoli, and the Nek2A-specific C-terminal end (amino acids 399-445) was responsible for nucleolar localization. Endogenous Nek11 coimmunoprecipitated with endogenous Nek2A, and non-catalytic regions of each kinase were involved in the complex formation. Nek11L interacted with phosphorylated Nek2A but barely with the kinase-inactive Nek2A (K37R) mutant. In addition, both Nek2A autophosphorylation activity and the Nek11L-Nek2A complex formation increased in G 1/S-arrested cells. These results indicate that autophosphorylation of Nek2A could stimulate its interaction with Nek11L at the nucleolus. Moreover, Nek2 directly phosphorylated Nek11 in the C-terminal non-catalytic region and elevated Nek11 kinase activity. The non-catalytic region of Nek11 showed autoinhibitory activity through intramolecular interaction with its N-terminal catalytic domain. Nek2 dissociated this autoinhibitory interaction. Altogether, our studies demonstrate a unique mechanism of Nek11 activation by Nek2A in G1/S-arrested cells and suggest a novel possibility for nucleolar function of the NIMA family.

Original languageEnglish
Pages (from-to)32716-32727
Number of pages12
JournalJournal of Biological Chemistry
Volume279
Issue number31
DOIs
Publication statusPublished - 2004 Jul 30
Externally publishedYes

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Phosphotransferases
Mitosis
Catalytic Domain
Amino Acids
Chemical activation
NIMA-Related Kinases

ASJC Scopus subject areas

  • Biochemistry

Cite this

Nucleolar Nek11 is a novel target of Nek2A in G1/S-arrested cells. / Noguchi, Kohji; Fukazawa, Hidesuke; Murakami, Yuko; Uehara, Yoshimasa.

In: Journal of Biological Chemistry, Vol. 279, No. 31, 30.07.2004, p. 32716-32727.

Research output: Contribution to journalArticle

Noguchi, K, Fukazawa, H, Murakami, Y & Uehara, Y 2004, 'Nucleolar Nek11 is a novel target of Nek2A in G1/S-arrested cells', Journal of Biological Chemistry, vol. 279, no. 31, pp. 32716-32727. https://doi.org/10.1074/jbc.M404104200
Noguchi, Kohji ; Fukazawa, Hidesuke ; Murakami, Yuko ; Uehara, Yoshimasa. / Nucleolar Nek11 is a novel target of Nek2A in G1/S-arrested cells. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 31. pp. 32716-32727.
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