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De la progestérone à l'activation du MPF dans l'ovocyte de Xénope: Quels rôles pour H-Ras et la kinase Myt1?

Abstract : The main objective of this PhD work was to unravel the mechanisms allowing the activation
of the molecular engine driving entry into mitosis in eukaryotic cells: MPF (M-Phase
promoting Factor). For this purpose, meiotic divisions of the Xenopus oocytes were selected
as a model system. Xenopus oocytes are naturally arrested in prophase of the first meiotic
division. After progesterone stimulation, they complete the first meiotic division and arrest at
metaphase II. This process depends on the activation of MPF (M-phase promoting factor), a
complex between Cyclin B and the Cyclin dependent kinase, Cdc2. Our goal was to study the
regulation of the Cdc2 kinase during the meiotic maturation process. We have first studied the
regulation of the Myt1 kinase, a member of the Wee1 family. The role of these kinases is to
phosphorylate Cdc2 on an inhibitory residue, Y15, hereby maintaining MPF under an inactive
state during G2 phase of the cell cycle. We have shown that Cdc2 itself is the central player
coordinating Myt1 inhibition. Furthermore, we have demonstrated that either the
Mos/MAPK/p90Rsk pathway or Plx1 (the homolog of the drosophila Polo kinase) are
recruited by Cdc2 and involved in the inhibition of Myt1. We then studied the implication of
the small G protein H-Ras in the resumption of meiosis. We have shown that the injection of
H-Ras in Xenopus oocytes induces the resumption of meiosis through the recruitment of a
particular PI3 Kinase, independently of its other known effectors, the Raf/MAPK pathway
and RalGDS. However, although the H-Ras/PI3K pathway is functional in Xenopus oocyte, it
is not the physiological transducer of progesterone responsible for meiotic resumption. In
conclusion, altogether these results show that Xenopus oocytes can activate functionally
redundant pathways that can lead to MPF activation. Some of them are preferentially
recruited by progesterone under physiological conditions. The other ones might rescue MPF
activation under pathological situations, where the first ones are defectives.
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Contributor : Melina Gaffré Pocard <>
Submitted on : Friday, October 19, 2007 - 2:23:57 PM
Last modification on : Thursday, December 10, 2020 - 10:55:02 AM
Long-term archiving on: : Monday, September 24, 2012 - 2:10:43 PM


  • HAL Id : tel-00180525, version 1


Melina Gaffré Pocard. De la progestérone à l'activation du MPF dans l'ovocyte de Xénope: Quels rôles pour H-Ras et la kinase Myt1?. Biologie de la reproduction. Université Pierre et Marie Curie - Paris VI, 2007. Français. ⟨tel-00180525⟩



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