Xenopus H-RasV12 promotes entry into meiotic M phase and cdc2 activation independently of Mos and p42MAPK

Abstract

In the Xenopus oocyte, progesterone triggers M phase Promoting Factor (MPF) activation in a protein synthesis dependent manner. Although the synthesis of the p42 MAPK activator Mos appears to be required for MPF activation, p42 MAPK activity has been shown to be dispensable. To clarify this paradox, we attempted to activate the p42 MAPK pathway independently of Mos synthesis by cloning and using Xenopus H-Ras in the oocyte. We demonstrate that the injection of the constitutively active Xe H-RasV12 mutant induces p42 MAPK and MPF activation through two independent pathways. Xe H-RasV12 induces only a partial activation of p42 MAPK when protein synthesis and MPF activation are prevented. A full level of p42 MAPK activation is reached when MPF is activated and Mos is present. In contrast, MPF activation induced by Xe HRasV12 is achieved independently of Mos synthesis and p42 MAPK activation but still depends on protein synthesis. Therefore, the amphibian oocyte represents a new model system to analyse an original H-Ras pathway ending to MPF activation and distinct from the p42 MAPK pathway. The identification of the proteins synthesized in response to Xe H-RasV12 and required for MPF activation, represents an important clue in understanding the mechanism of progesterone action.

O-Linked N-Acetylglucosaminyltransferase Inhibition Prevents G2/M Transition in Xenopus laevis Oocytes

“…It should be also noted that O-GlcNAc level immediately increases after hormonal stimulation (2 h post-progesterone; data not shown), indicating that O-GlcNAc is necessary for the early steps of the G 2 /M transition. Because MAPK activity or cyclin B synthesis is not essential for M-phase entry in Xenopus oocytes (17,18,21,47), mechanisms sensitive to O-GlcNAc variation, which are essential for G 2 /M transition, remain to be elucidated.…”

Three steps to the immortality of cancer cells: senescence, polyploidy and self-renewal

“…In female meiosis, activated Mos causes oocyte maturation – inducing the first meiotic division of the oocytes paused at G2 phase-like prophase (by activating cdk1/cyclin B1), triggering interkinesis with suppression of DNA synthesis, and causing the subsequent arrest at the spindle checkpoint of meiosis II. Here, Mos prevents parthenogenesis in the mature oocytes awaiting fertilisation, through the MEK-pMAPK42-Rsk90 complex and also by acting directly on the meiotic spindle [59,63,67-69]. Mos is downstream of Ras in meiosis and equivalent to Raf in the Ras-MEK-MAPK proliferative pathway.…”

“…Moreover, mutant H-ras Val12 is nearly 100-times more potent at inducing maturation [77]. It, unlike Mos, does not need stimulation by progesterone and can promote entry into meiotic M phase and cdk1 activation independently of Mos [69]. Clearly then the molecular pathways induced by DNA damage and involved in the illicit transition to tetraploidy and accelerated senescence (which should terminate proliferation), are intrinsically associated with the molecular pathways of gametogenesis and early embryogenesis (which, in contrast, can restore immortality and re-initiate the life-cycle) potentially allowing this switch between them.…”

A G Protein-coupled Receptor Kinase Induces XenopusOocyte Maturation

“…To rule out general toxicity or other nonspecific effects of the inhibitors in oocytes, we tested the effects of these inhibitors on v-Rasinduced GVBD. Although the mechanism by which v-Ras induces GVBD remains controversial (27), it is unlikely that it would require receptor endocytosis. Indeed, neither Con A (Fig.…”