Tyrosine kinase Pyk2 mediates G-protein-coupled receptor regulation of the Ewing sarcoma RNA-binding protein EWS

被引:38
作者
Felsch, JS
Lane, WS
Peralta, EG
机构
[1] Harvard Univ, Dept Cellular & Mol Biol, Cambridge, MA 02138 USA
[2] Harvard Univ, Harvard Microchem Facil, Cambridge, MA 02138 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S0960-9822(99)80214-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ewing family tumors result from the effects of chromosomal translocations that fuse the Ewing sarcoma (EWS) gene to various genes encoding transcription factors [1], The resulting chimeric EWS fusion proteins are transcriptional activators with transforming potential that have received much study [2]. By contrast, the cellular function of somatic EWS remains obscure. EWS belongs to a family of RNA-binding proteins thought to play role in RNA synthesis or processing [3,4]. Here, we show that EWS interacts with Pyk2, a protein tyrosine kinase implicated in a variety of signal transduction processes [5-8]. G-protein-coupled receptor signaling and other stimuli of Pyk2 kinase activity significantly block the interaction between EWS and Pyk2, Furthermore, as assessed by sucrose gradient centrifugation, EWS partitions with dense ribosome-containing fractions in a manner that is enhanced by signaling from the G-protein-coupled mi muscarinic acetylcholine receptor (mAChR). We conclude that extranuclear EWS is a previously unrecognized target of G-protein-coupled receptor regulation.
引用
收藏
页码:485 / 488
页数:4
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