Regulation of xenopus p21-activated kinase (X-PAK2) by Cdc42 and maturation-promoting factor controls Xenopus oocyte maturation

Signal transduction cascades involved in regulation of the cell cycle machi nery are poorly understood. In the Xenopus oocyte model, meiotic maturation is triggered by MPF, a complex of p34(cdc2)-cyclin B, which is activated i n response to a progesterone signal by largely unknown mechanisms. We have previously shown that the p21-activated kinase (PAK) family negatively regu lates the MPF amplification loop. In this study, we identify the endogenous PAK2 as a key enzyme in this regulation and describe the pathways by which PAK2 is regulated. We show that the small GTPase Cdc42 is required for mai ntenance of active endogenous X-PAK2 in resting stage VI oocytes, whereas R ad is not involved in this regulation. During the process of maturation, X- PAK2 phosphorylation results in its inactivation and allows maturation to p roceed to completion Activation of mitogen-activated protein kinase and cyc lin B-p34(cdc2) is coincident with X-PAK2 inactivation, and purified active MPF inhibits X-PAK2, demonstrating the existence of a new positive feedbac k loop. Our results confirm and extend the importance of p21-activated kina ses in the control of the G(2)/M transition. We hypothesize that the X-PAK2 /Cdc42 pathway could link p34(cdc2) activity to the major cytoskeleton rear rangements leading to spindle migration and anchorage to the animal pole co rtex.