The kinase Eg2 is a component of the Xenopus oocyte progesterone-activated signaling pathway

The kinase Eg2 is a component of the Xenopus oocyte progesterone-activated signaling pathway
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DOI:
10.1093/emboj/17.19.5627
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发表时间:
1998-10-01
期刊:
影响因子:
11.4
通讯作者:
Ruderman, JV
Ruderman, JV
中科院分区:
生物学1区
文献类型:
--
作者:
Andrésson, T;Ruderman, JV

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静止的非洲爪蟾卵母细胞被孕酮激活,孕酮与一种未识别的表面相关受体结合。孕激素激活一种知之甚少的信号传导途径,导致编码Mos的mRNA的翻译激活,Mos是MAP激酶和MPF激活所必需的MAP激酶;减数分裂的恢复,以及卵母细胞成熟为精子响应性卵子。我们设计了一种筛选方法来鉴定早期信号蛋白,其前提是这些蛋白中的一些在加入孕酮后几分钟内会被磷酸化或以其他方式修饰。我们发现Eg 2在孕酮刺激后很快被磷酸化,并提供了它在信号通路中起作用的证据。通过mRNA显微注射过量表达Eg 2缩短了孕酮刺激和新Mos蛋白出现之间的时间,加速了MAP激酶的激活并提前进入减数分裂细胞周期。最后,Eg 2的过度表达显著降低了触发卵母细胞激活所需的孕酮浓度。这些结果表明,激酶Eg 2是孕酮激活的信号通路的一个组成部分,释放青蛙卵母细胞从细胞周期停滞。
Quiescent Xenopus oocytes are activated by progesterone, which binds to an unidentified surface-associated receptor. Progesterone activates a poorly understood signaling pathway that results in the translational activation of mRNA encoding Mos, a MAP kinase kinase kinase necessary for the activation of MAP kinase and MPF; the resumption of meiosis, and maturation of the oocyte into the sperm-responsive egg. We have designed a screen to identify early signaling proteins based on the premise that some of these proteins would be phosphorylated or otherwise modified within minutes of progesterone addition. This screen has revealed Eg2, a Ser/Thr kinase, We find that Eg2 is phosphorylated soon after progesterone stimulation and provide evidence that it functions in the signaling pathway. Overexpression of Eg2 via mRNA microinjection shortens the time between progesterone stimulation and the appearance of new Mos protein, accelerates activation of MAP kinase and advances entry into the meiotic cell cycle. Finally, overexpression of Eg2 dramatically reduces the concentration of progesterone needed do trigger oocyte activation. These results argue that the kinase Eg2 is a component of the progesterone-activated signaling pathway that releases frog oocytes from cell cycle arrest.