The critical role of the MAP kinase pathway in meiosis II in Xenopus oocytes is mediated by p90(Rsk)

Curr Biol. 2000 Apr 20;10(8):430-8. doi: 10.1016/s0960-9822(00)00425-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Butadienes / pharmacology
  • Cell Cycle Proteins / metabolism
  • Cyclin B / metabolism
  • DNA Replication / drug effects
  • Enzyme Inhibitors / pharmacology
  • Female
  • Immunoblotting
  • Meiosis* / drug effects
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Mutation
  • Nitriles / pharmacology
  • Oocytes / cytology
  • Oocytes / drug effects
  • Oocytes / enzymology*
  • Polymerase Chain Reaction
  • Progesterone / pharmacology
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Serine-Threonine Kinases / pharmacology
  • Ribosomal Protein S6 Kinases / antagonists & inhibitors
  • Ribosomal Protein S6 Kinases / genetics
  • Ribosomal Protein S6 Kinases / metabolism*
  • Xenopus
  • Xenopus Proteins*
  • cdc25 Phosphatases / metabolism

Substances

  • Butadienes
  • Cell Cycle Proteins
  • Cyclin B
  • Enzyme Inhibitors
  • Nitriles
  • U 0126
  • Xenopus Proteins
  • Progesterone
  • Protein Kinases
  • Plk1 protein, Xenopus
  • Protein-Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • cdc25 Phosphatases