Kicked by Mos and tuned by MPF-the initiation of the MAPK cascade in Xenopus oocytes.

The mitogen-activated protein kinase (MAPK) cascade is a paradigmatic signaling cascade, which plays a crucial role in many aspects of cellular events. The main initiator of the cascade in Xenopus oocytes is the oncoprotein Mos. After activation of the cascade, Mos activity is stabilized by MAPK via a feedback loop. Mos concentration levels are, however, not controlled by MAPK alone. In this paper we show, by imposing either a sustained or a peaked activity of M-phase promoting factor (MPF) (Cdc2-cyclin B), how the latter regulates the dynamics of Mos. Our experiments are supported by a detailed kinetic model for the Mos-MPF-MAPK network, which takes into account the three different phosphorylation states of Mos and, as a consequence, allows us to determine the time evolution of Mos under control of MPF. Our work opens a path toward a more complete and biologically realistic quantitative understanding of the dynamic interdependence of Mos and MPF in Xenopus oocytes.