Protein kinase WNK3 regulates the neuronal splicing factor Fox-1

被引：16
|
作者：
Lee, A-Young [1 ]
Chen, Wei [1 ]
Stippec, Steve [1 ]
Self, Jon [1 ]
Yang, Fan [2 ]
Ding, Xiaojun [2 ]
Chen, She [2 ]
Juang, Yu-Chi [1 ]
Cobb, Melanie H. [1 ]
机构：
[1] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA
[2] Natl Inst Biol Sci, Beijing 102206, Peoples R China
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 42期
基金：
美国国家卫生研究院;
关键词：
cytoplasmic retention; FMNL3; PRE-MESSENGER-RNA; AUTISM; GENE; XP11.22-P11.23; RECOGNITION; HOMOLOGS; BRAIN;
D O I：
10.1073/pnas.1215406109
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
We report an action of the protein kinase WNK3 on the neuronal mRNA splicing factor Fox-1. Fox-1 splices mRNAs encoding proteins important in synaptic transmission and membrane excitation. WNK3, implicated in the control of neuronal excitability through actions on ion transport, binds Fox-1 and inhibits its splicing activity in a kinase activity-dependent manner. Phosphorylation of Fox-1 by WNK3 does not change its RNA binding capacity; instead, WNK3 increases the cytoplasmic localization of Fox-1, thereby suppressing Fox-1-dependent splicing. These findings demonstrate a role of WNK3 in RNA processing. Considering the implication of WNK3 and Fox-1 in disorders of neuronal development such as autism, WNK3 may offer a target for treatment of Fox-1-induced disease.
引用
收藏
页码：16841 / 16846
页数：6
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