The Clk2 and Clk3 dual-specificity protein kinases regulate the intranuclear distribution of SR proteins and influence pre-mRNA splicing

被引:127
作者
Duncan, PI
Stojdl, DF
Marius, RM
Scheit, KH
Bell, JC
机构
[1] Ottawa Reg Canc Ctr, Ottawa, ON K1H 8L6, Canada
[2] Max Planck Inst Biophys Chem, Mol Biol Abt, D-37077 Gottingen, Germany
关键词
D O I
10.1006/excr.1998.4083
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The three members of the Clk family of kinases (Clk1, 2, and 3) have been shown to undergo conserved alternative splicing to generate catalytically active (Clk) and inactive (Clk(T)) isoforms. The prototype, murine Clk1 (mClk1), is a nuclear dual-specificity kinase that can interact with, and cause the nuclear redistribution of, SR proteins. In this study, we demonstrate that the human Clk2 and Clk3 (hClk2 and 3) are also found within the nucleus and display dual-specificity kinase activity. The truncated isoforms, hClk2(T) and hClk3(T), colocalize with SR proteins in nuclear speckles. We also show catalytically active hClk2 and hClk3 cause the redistribution of SR proteins and can regulate the alternative splicing of a model precursor mRNA substrate in vivo. (C) 1998 Academic Press.
引用
收藏
页码:300 / 308
页数:9
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