The prooncoprotein EWS binds calmodulin and is phosphorylated by protein kinase C through an IQ domain
The prooncoprotein EWS binds calmodulin and is phosphorylated by protein kinase C through an IQ domain
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DOI：
10.1074/jbc.272.43.27369
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发表时间：
1997-10-24
影响因子：
4.8
通讯作者：
Storm, DR
中科院分区：
文献类型：
--
作者：
Deloulme, JC;Prichard, L;Storm, DR
一个不断增长的蛋白质家族由蛋白激酶C和钙调蛋白通过IQ结构域调节，IQ结构域是最初在神经调蛋白中鉴定的调节基序（亚历山大，K.一、瓦基姆，B。T.，Doyle，G.美国，沃尔什，K.一、Storm，D. R.（1988）J. Biol. Chem，263，7544-7549）。在这里，我们报告了EWS，一种核RNA结合原癌蛋白，含有IQ结构域，被蛋白激酶C磷酸化，并与钙调蛋白相互作用。有趣的是，EWS的PKC磷酸化抑制其与RNA均聚物的结合，相反，RNA与EWS的结合干扰PKC磷酸化。其他几种RNA结合蛋白，包括TLS/FUS和PSF，与EWS共纯化，这些蛋白质的PKC磷酸化也抑制它们在体外与RNA的结合。这些数据表明，PKC可以调节EWS和其他RNA结合蛋白与其RNA靶点的相互作用，IQ结构域可以提供Ca 2+信号转导途径和RNA加工之间的调节联系。
A growing family of proteins is regulated by protein kinase C and calmodulin through IQ domains, a regulatory motif originally identified in neuromodulin (Alexander, K. A., Wakim, B. T., Doyle, G. S., Walsh, K. A., and Storm, D. R. (1988) J. Biol. Chem, 263, 7544-7549). Here we report that EWS, a nuclear RNA-binding proonco-protein, contains an IQ domain, is phosphorylated by protein kinase C, and interacts with calmodulin, Interestingly, PKC phosphorylation of EWS inhibits its binding to RNA homopolymers, and conversely, RNA binding to EWS interferes with PKC phosphorylation, Several other RNA-binding proteins, including TLS/FUS and PSF, co-purify with EWS, PKC phosphorylation of these proteins also inhibits their binding to RNA in vitro. These data suggest that PKC may regulate interactions of EWS and other RNA-binding proteins with their RNA targets and that IQ domains may provide a regulatory link between Ca2+ signal transduction pathways and RNA processing.