title: The critical role of the MAP kinase pathway in meiosis II in Xenopus oocytes is mediated by p90(Rsk).
abstract: BACKGROUND
  During oocyte maturation in Xenopus, progesterone induces entry into meiosis I, and the M phases of meiosis I and II occur consecutively without an intervening S phase. The mitogen-activated protein (MAP) kinase is activated during meiotic entry, and it has been suggested that the linkage of M phases reflects activation of the MAP kinase pathway and the failure to fully degrade cyclin B during anaphase I. To analyze the function of the MAP kinase pathway in oocyte maturation, we used U0126, a potent inhibitor of MAP kinase kinase, and a constitutively active mutant of the protein kinase p90(Rsk), a MAP kinase target.
  
  
  RESULTS
  Even with complete inhibition of the MAP kinase pathway by U0126, up to 90% of oocytes were able to enter meiosis I after progesterone treatment, most likely through activation of the phosphatase Cdc25C by the polo-like kinase Plx1. Subsequently, however, U0126-treated oocytes failed to form metaphase I spindles, failed to reaccumulate cyclin B to a high level and failed to hyperphosphorylate Cdc27, a component of the anaphase-promoting complex (APC) that controls cyclin B degradation. Such oocytes entered S phase rather than meiosis II. U0126-treated oocytes expressing a constitutively active form of p90(Rsk) were able to reaccumulate cyclin B, hyperphosphorylate Cdc27 and form metaphase spindles in the absence of detectable MAP kinase activity.
  
  
  CONCLUSIONS
  The MAP kinase pathway is not essential for entry into meiosis I in Xenopus but is required during the onset of meiosis II to suppress entry into S phase, to regulate the APC so as to support cyclin B accumulation, and to support spindle formation. Moreover, one substrate of MAP kinase, p90(Rsk), is sufficient to mediate these effects during oocyte maturation.
authors.affiliation: Department of Pharmacology, Howard Hughes Medical Institute, University of Colorado School of Medicine, Denver, CO 80262-0236, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Gross
authors.forename: M S
authors.initials: MS
authors.lastname: Schwab
authors.forename: F E
authors.initials: FE
authors.lastname: Taieb
authors.forename: A L
authors.initials: AL
authors.lastname: Lewellyn
authors.forename: Y W
authors.initials: YW
authors.lastname: Qian
authors.forename: J L
authors.initials: JL
authors.lastname: Maller
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015151:Immunoblotting; D008540:Meiosis / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009154:Mutation; D009570:Nitriles / Q000494:pharmacology; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D011374:Progesterone / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000494:pharmacology; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins; D020687:cdc25 Phosphatases / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D002070:Butadienes; D018797:Cell Cycle Proteins; D019926:Cyclin B; D004791:Enzyme Inhibitors; D020929:Mitogen-Activated Protein Kinase Kinases; D009570:Nitriles; D011374:Progesterone; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D029867:Xenopus Proteins; D020687:cdc25 Phosphatases; C113580:U 0126; C101085:Plk1 protein, Xenopus; D000097869:Polo-Like Kinase 1