INITIATION OF XENOPUS OOCYTE MATURATION BY ACTIVATION OF THE MITOGEN-ACTIVATED PROTEIN-KINASE CASCADE

Mitogen-activated protein kinase (MAPK) and MAPK kinase (MAPKK) are ac tivated during Xenopus oocyte maturation concomitant with the activati on of maturation promoting factor (MPF). We reported previously that a n anti-MAPKK neutralizing antibody inhibited progesterone- or Mos- ind uced initiation of oocyte maturation. Here, we show that injection of CL100 (also called MAPK phosphatase-1) into immature oocytes inhibited progesterone-induced oocyte maturation as well as MAPK activation and that injection of mRNA encoding a constitutively active MAPKK induced activation of histone H1 kinase and germinal vesicle breakdown in the absence of progesterone. Injection of recombinant STE11 protein (a ye ast MAPKK kinase) also induced initiation of oocyte maturation. These data support the idea that the MAPKK/MAPK cascade plays an important r ole in oocyte maturation. Interestingly, injection of the active MAPKK mRNA or the STE11 protein resulted in induction and accumulation of M os protein. Furthermore, in the presence of cycloheximide, the STE11-i nduced activation of MPF as well as the induction and accumulation of Mos was blocked, and the activation of MAPK was greatly reduced. The i ncrease in Mos protein and the activation of MAPK by injecting cyclin A protein into immature oocytes were both blocked also by cycloheximid e treatment. These results are consistent with an idea that there may exist a positive feedback loop consisting of Mos, the MAPKK/MAPK casca de, and MPF, which may be important for the initiation of oocyte matur ation induced by progesterone.