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

Background: During oocyte maturation in Xenopus, progesterone induces entry into meiosis I, and the M phases of meiosis I and II occur consecutively w ithout an intervening S phase. The mitogen-activated protein (MAP) kinase i s activated during meiotic entry, and it has been suggested that the linkag e 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 th e MAP kinase pathway in oocyte maturation, we used U0126, a potent inhibito r of MAP kinase kinase, and a constitutively active mutant of the protein k inase 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 treatm ent, most likely through activation of the phosphatase Cdc25C by the polo-l ike kinase Plx1. Subsequently, however, U0126-treated oocytes failed to for m 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 ph ase rather than meiosis II. U0126-treated oocytes expressing a constitutive ly active form of p90(Rsk) were able to reaccumulate cyclin B, hyperphospho rylate Cdc27 and form metaphase spindles in the absence of detectable MAP k inase 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 en try into S phase, to regulate the APC so as to support cyclin B accumulatio n, and to support spindle formation. Moreover, one substrate of MAP kinase, p90(Rsk), is sufficient to mediate these effects during oocyte maturation.