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通过激活丝裂原活化蛋白激酶级联反应启动非洲爪蟾卵母细胞成熟。

Initiation of Xenopus oocyte maturation by activation of the mitogen-activated protein kinase cascade.

作者信息

Gotoh Y, Masuyama N, Dell K, Shirakabe K, Nishida E

机构信息

Department of Genetics and Molecular Biology, Kyoto University, Japan.

出版信息

J Biol Chem. 1995 Oct 27;270(43):25898-904. doi: 10.1074/jbc.270.43.25898.

DOI:10.1074/jbc.270.43.25898
PMID:7592777
Abstract

Mitogen-activated protein kinase (MAPK) and MAPK kinase (MAPKK) are activated during Xenopus oocyte maturation concomitant with the activation of maturation promoting factor (MPF). We reported previously that an anti-MAPKK neutralizing antibody inhibited progesterone- or Mos- induced initiation of oocyte maturation. Here, we show that the injection of CL100 (also called MAPK phosphatase-1) into immature oocytes inhibited progesterone-induced oocyte maturation as well as MAPK activation and that injection of mRNA encoding a constitutively active MAPKK induced activation of histone H1 kinase and germinal vesicle breakdown in the absence of progesterone. Injection of recombinant STE11 protein (a yeast MAPKK kinase) also induced initiation of oocyte maturation. These data support the idea that the MAPKK/MAPK cascade plays an important role in oocyte maturation. Interestingly, injection of the active MAPKK mRNA or the STE11 protein resulted in induction and accumulation of Mos protein. Furthermore, in the presence of cycloheximide, the STE11-induced activation of MPF as well as the induction and accumulation of Mos was blocked, and the activation of MAPK was greatly reduced. The increase in Mos protein and the activation of MAPK by injecting cyclin A protein into immature oocytes were both blocked also by cycloheximide treatment. These results are consistent with an idea that there may exist a positive feedback loop consisting of Mos, the MAPKK/MAPK cascade, and MPF, which may be important for the initiation of oocyte maturation induced by progesterone.

摘要

在非洲爪蟾卵母细胞成熟过程中,丝裂原活化蛋白激酶(MAPK)和MAPK激酶(MAPKK)伴随着成熟促进因子(MPF)的激活而被激活。我们之前报道过,一种抗MAPKK中和抗体可抑制孕酮或Mos诱导的卵母细胞成熟起始。在此,我们表明向未成熟卵母细胞中注射CL100(也称为MAPK磷酸酶-1)可抑制孕酮诱导的卵母细胞成熟以及MAPK激活,并且注射编码组成型活性MAPKK的mRNA可在无孕酮的情况下诱导组蛋白H1激酶激活和生发泡破裂。注射重组STE11蛋白(一种酵母MAPKK激酶)也可诱导卵母细胞成熟起始。这些数据支持MAPKK/MAPK级联在卵母细胞成熟中起重要作用这一观点。有趣的是,注射活性MAPKK mRNA或STE11蛋白会导致Mos蛋白的诱导和积累。此外,在存在环己酰亚胺的情况下,STE11诱导的MPF激活以及Mos的诱导和积累被阻断,并且MAPK的激活大幅降低。通过向未成熟卵母细胞中注射细胞周期蛋白A蛋白所导致的Mos蛋白增加和MAPK激活也都被环己酰亚胺处理所阻断。这些结果与以下观点一致,即可能存在一个由Mos、MAPKK/MAPK级联和MPF组成的正反馈环,这可能对孕酮诱导的卵母细胞成熟起始很重要。

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