Xenopus H-RasV12 promotes entry into meiotic M phase and cdc2 activation independently of Mos and p42(MAPK).
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 H-RasV12 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.
Dupré
Aude
A
Laboratoire de Biologie du Développement, INRA/UMR-CNRS 7622, Université Pierre et Marie Curie, boîte 24, 4 place Jussieu, 75252 Paris Cedex 05, France.
Suziedelis
Kestutis
K
Valuckaite
Ryte
R
de Gunzburg
Jean
J
Ozon
René
R
Jessus
Catherine
C
Haccard
Olivier
O
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D011905:Genes, ras / Q000502:physiology*; D016200:Maturation-Promoting Factor / Q000378:metabolism*; D008540:Meiosis / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D017231:Proto-Oncogene Proteins c-mos / Q000235:genetics* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014982:Xenopus laevis
D010726:Phosphodiesterase Inhibitors; D011500:Protein Synthesis Inhibitors; D000242:Cyclic AMP; D017231:Proto-Oncogene Proteins c-mos; D016203:CDC2 Protein Kinase; D016200:Maturation-Promoting Factor; D019950:Mitogen-Activated Protein Kinase 1; D015056:1-Methyl-3-isobutylxanthine