Ribosomal S6 kinase p90rsk and mRNA cap-binding protein eIF4E phosphorylations correlate with MAP kinase activation during meiotic reinitiation of mouse oocytes.
During meiotic reinitiation of the mouse oocyte, entry into M-phase is regulated by changes of protein phosphorylation and by the stimulation of selective mRNA translation following the nuclear membrane dissolution. Our results reveal that M-phase kinases (MAP kinase and histone H1 kinase) are being activated together with S6 kinase and with the phosphorylation of eIF4E, the cap-binding subunit of the initiation factor eIF-4F. In order to test which signaling pathway(s) is(are) involved, okadaic acid and cycloheximide have been used as tools for differentially modulating MAP and histone H1 kinase activities. A role for MAP kinases in the phosphorylation of eIF4E and the activation of S6 kinase is suggested. The possible implication of p90rsk and/or of p70s6k in the overall increase in S6 kinase activity has been examined. p70s6k does not appear to be involved since phosphorylated forms are found in prophase and maturing oocytes. In contrast, p90rsk is phosphorylated and activated in maturing oocytes. p90rSk phosphorylation correlates with the activation of S6 kinase. These results suggest that the overall increase of S6 kinase activity is mostly due to p90rsk activation. The roles of eIF4E phosphorylation and S6 kinase activation in the physiological induction of M-phase and in the okadaic acid-induced premature mitotic events are discussed.
Gavin
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Clinique de Stérilité et d'Endocrinologie Gynécologique, Department of Obstetrics and Gynaecology, Hôpital Cantonal Universitaire, Geneva,Switzerland.
Schorderet-Slatkine
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D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D039561:Eukaryotic Initiation Factor-4E; D005260:Female; D008540:Meiosis; D051379:Mice; D019319:Okadaic Acid / Q000494:pharmacology; D009865:Oocytes / Q000166:cytology*; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D039381:RNA Cap-Binding Proteins; D012315:RNA Caps / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases; D015398:Signal Transduction
D004791:Enzyme Inhibitors; D039561:Eukaryotic Initiation Factor-4E; D010448:Peptide Initiation Factors; D011500:Protein Synthesis Inhibitors; D039381:RNA Cap-Binding Proteins; D012315:RNA Caps; D016601:RNA-Binding Proteins; D019319:Okadaic Acid; D003513:Cycloheximide; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases