Gaffré M, Dupré A, Valuckaite R, Suziedelis K, Jessus C, Haccard O
Laboratoire de Biologie du Développement, UMR-CNRS 7622, Université Pierre et Marie Curie, Paris, France.
Oncogene. 2006 Aug 24;25(37):5155-62. doi: 10.1038/sj.onc.1209523. Epub 2006 Apr 10.
Xenopus oocytes are arrested in prophase of the first meiotic division. In response to progesterone, they re-enter meiosis and arrest again in metaphase of the second meiotic division. This process, called meiotic maturation, is under the control of the Cyclin B-Cdc2 complex, M phase promoting factor (MPF). Injection of a constitutively active Xenopus H-Ras protein activates MPF, suggesting that Ras proteins could be implicated in the progesterone transduction pathway. The aim of this study was (1) to elucidate the pathway triggered by H-Ras leading to MPF activation in Xenopus oocytes and (2) to investigate whether endogenous H-Ras is involved in the physiological process of meiotic maturation. We generated three constitutively active double mutants, each of them recruiting a single effector in mammalian cells, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K) or RalGDS. Our results show that the activation of a PI3K-related enzyme is crucial for H-Ras-induced MPF activation, whereas the recruitment of either MAPK or RalGDS is not. However, although the H-Ras/PI3K pathway is functional in Xenopus oocytes, it is not the physiological transducer of progesterone responsible for meiotic resumption.
非洲爪蟾卵母细胞停滞于第一次减数分裂的前期。在孕酮的作用下，它们重新进入减数分裂，并再次停滞于第二次减数分裂的中期。这个过程称为减数分裂成熟，受细胞周期蛋白B - Cdc2复合物即M期促进因子（MPF）的调控。注射组成型激活的非洲爪蟾H - Ras蛋白可激活MPF，这表明Ras蛋白可能参与孕酮信号转导途径。本研究的目的是：（1）阐明非洲爪蟾卵母细胞中由H - Ras触发并导致MPF激活的信号通路；（2）研究内源性H - Ras是否参与减数分裂成熟的生理过程。我们构建了三个组成型激活的双突变体，每个突变体在哺乳动物细胞中募集单一效应分子，即丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇3 -激酶（PI3K）或RalGDS。我们的结果表明，PI3K相关酶的激活对于H - Ras诱导的MPF激活至关重要，而募集MAPK或RalGDS则并非如此。然而，尽管H - Ras/PI3K信号通路在非洲爪蟾卵母细胞中具有功能，但它并非负责减数分裂恢复的孕酮的生理转导分子。
