PROGESTERONE BUT NOT RAS REQUIRES MPF FOR IN-VIVO ACTIVATION OF MAPK AND S6 KII - MAPK IS AN ESSENTIAL CONNECTION POINT OF BOTH SIGNALING PATHWAYS

Induction of mitosis in Xenopus laevis oocytes by hormones and the onc ogenic ras-p21 protein has been shown to correlate with a cascade of p hosphorylations of the Ser/Thr family of kinases. However, the exact h ierarchy of enzymes and their mutual interdependency has not been full y elucidated yet. We have used the Xenopus laevis system to investigat e the mechanism of activation of the Ser/Thr kinases cascade and their relationship. Comparison between progesterone-induced germinal vesicl e breakdown (GVBD), a hallmark of mitosis in oocytes, to that triggere d by ras-p21, revealed the existence of at least two independent mecha nisms to activate the MAP kinase enzyme in vivo. While progesterone fu nction is dependent of cdc2 protein kinase activity, ras-p21 is indepe ndent of this enzyme. However, both progesterone and ras-p21 converge at the MAP kinase level, and depletion of MAP kinase activity inhibits the GVBD and S6 kinase II activation induced by both progesterone and ras-p21. These results provides further evidence that MAP kinase is a critical step for regulation of the cell cycle in oocytes and a criti cal point where ras and progesterone signaling converge. (C) 1994 Wile y-Liss, Inc.