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. 2008 Oct 3;24(5):271–277. doi: 10.1007/s12264-008-0605-5

Casein kinase 2 interacts with and phosphorylates ataxin-3

酪蛋白激酶2结合并磷酸化ataxin-3

Rui-Song Tao 1,2, Er-Kang Fei 1,✉, Zheng Ying 1, Hong-Feng Wang 1, Guang-Hui Wang 1
PMCID: PMC5552532  PMID: 18839019

Abstract

Objective

Machado-Joseph disease (MJD)/Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by an expansion of polyglutamine tract near the C-terminus of the MJD1 gene product, ataxin-3. The precise mechanism of the MJD/SCA3 pathogenesis remains unclear. A growing body of evidence demonstrates that phosphorylation plays an important role in the pathogenesis of many neurodegenerative diseases. However, few kinases are known to phosphorylate ataxin-3. The present study is to explore whether ataxin-3 is a substrate of casein kinase 2 (CK2).

Methods

The interaction between ataxin-3 and CK2 was identified by glutathione S-transferase (GST) pull-down assay and co-immunoprecipition assay. The phosphorylation of ataxin-3 by CK2 was measured by in vitro phosphorylation assays.

Results

(1) Both wild type and expanded ataxin-3 interacted with CK2α and CK2β in vitro. (2) In 293 cells, both wild type and expanded ataxin-3 interacted with CK2β, but not CK2α. (3) CK2 phosphorylated wild type and expanded ataxin-3.

Conclusion

Ataxin-3 is a substrate of protein kinase CK2.

Keywords: Machado-Joseph disease/spinocerebellar ataxia type 3, ataxin-3, casein kinase 2, phosphorylation

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