Abstract
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.
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Acknowledgements
We thank J Moreau for the Xenopus RalB clones, A Hall for the rCD2p110 construct, R Wolthuis, D Du Pasquier and all the members of the laboratory for precious advice, and especially R Ozon for critical reading of the manuscript. This work was supported by grants from CNRS, University Pierre and Marie Curie, ARC (no. 3571 to CJ) and Ligue Nationale contre le Cancer (Equipe labellisée 2003 to CJ).
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Gaffré, M., Dupré, A., Valuckaite, R. et al. Deciphering the H-Ras pathway in Xenopus oocyte. Oncogene 25, 5155–5162 (2006). https://doi.org/10.1038/sj.onc.1209523
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DOI: https://doi.org/10.1038/sj.onc.1209523