Casein kinase 2 interacts with and phosphorylates ataxin-3  

酪蛋白激酶2结合并磷酸化ataxin-3(英文)

作　　者：陶瑞松[1,2] 费尔康[1] 应征[1] 王洪枫[1] 王光辉[1] 

机构地区：[1]中国科学技术大学合肥微尺度物质科学国家实验室,生命科学学院分子神经病理学实验室 [2]合肥师范学院生物系,合肥230061

出　　处：《Neuroscience Bulletin》2008年第5期271-277,共7页神经科学通报（英文版）

基　　金：the National Natural Sciences Foundation of China (No. 30770664);a grant from Educational Committee of Anhui Province, China (No. ZD2008008-2).

摘　　要：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.目的马查多-约瑟夫病/脊髓小脑共济失调3型,是由MJD1基因产物ataxin-3的C-末端的多聚谷氨酰胺发生重复扩展突变而引起的一种常染色体显性遗传的神经退行性疾病,目前它的发病机制还不清楚。很多研究表明磷酸化修饰作用在很多神经退行性疾病的发病过程中起到重要作用,然而已知可以磷酸化ataxin-3的激酶仍然很少。本研究的目的是探讨酪蛋白激酶2(Casein kinase 2,CK2)对于ataxin-3的磷酸化作用。方法通过GST pull-down和免疫共沉淀技术鉴定ataxin-3和CK2的相互作用。通过体外磷酸化技术检测CK2对ataxin-3的磷酸化。结果(1)正常和扩展突变型ataxin-3在体外与CK2α、β亚单位均发生相互作用;(2)在293细胞中正常和扩展突变型ataxin-3只和CK2β亚单位相互作用,而与α亚单位没有结合;(3)正常和扩展突变型ataxin-3都可以被CK2磷酸化。结论Ataxin-3是蛋白激酶CK2的底物。

关 键 词：Machado-Joseph disease/spinocerebellar ataxia type 3 ATAXIN-3 casein kinase 2 PHOSPHORYLATION 

分 类 号：Q42[生物学—神经生物学]