Interplay between Cdc2 kinase and the c-Mos/MAPK pathway between metaphaseI and metaphase II in Xenopus oocytes

Xenopus oocytes arrested in prophase I resume meiotic division in response to progesterone and arrest at metaphase II. Entry into meiosis I depends on the activation of Cdc2 kinase [M-phase promoting factor (MPF)]. To better understand the role of Cdc2, MPF activity was specifically inhibited by inj ection of the CDK inhibitor, Cip1. When Cip1 is injected at germinal vesicl e breakdown (GVBD) time, Cdc25 and Plx1 are both dephosphorylated and Cdc2 is rephosphorylated on tyrosine. The autoamplification loop characterizing MPF is therefore not only required for MPF generation before GVBD, but also for its stability during the GVBD period. The ubiquitine ligase anaphase-p romoting complex/cyclosome (APC/C), responsible for cyclin degradation, is also under the control of Cdc2; therefore, Cdc2 activity itself induces its own inactivation through cyclin degradation, allowing the exit from the fi rst meiotic division. In contrast, cyclin accumulation, responsible for Cdc 2 activity increase allowing entry into metaphase II, is independent of Cdc 2. The c-Mos/mitogen-activated protein kinase (MAPK) pathway remains active when Cdc2 activity is inhibited at GVBD time. This pathway could be respon sible for the sustained cyclin neosynthesis. In contrast, during the metaph ase II block, the c-Mos/MAPK pathway depends on Cdc2. Therefore, the metaph ase II block depends on a dynamic interplay between MPF and CSF, the c-Mos/ MAPK pathway stabilizing cyclin B, whereas in turn, MPF prevents c-Mos degr adation.