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

First Author  Cau J Year  2000
Journal  J Biol Chem Volume  275
Issue  4 Pages  2367-75
PubMed ID  10644687 Mgi Jnum  J:60205
Mgi Id  MGI:1352970 Doi  10.1074/jbc.275.4.2367
Citation  Cau J, et al. (2000) Regulation of Xenopus p21-activated kinase (X-PAK2) by Cdc42 and maturation-promoting factor controls Xenopus oocyte maturation. J Biol Chem 275(4):2367-75
abstractText  Signal transduction cascades involved in regulation of the cell cycle machinery are poorly understood. In the Xenopus oocyte model, meiotic maturation is triggered by MPF, a complex of p34(cdc2)-cyclin B, which is activated in response to a progesterone signal by largely unknown mechanisms. We have previously shown that the p21-activated kinase (PAK) family negatively regulates 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 maintenance of active endogenous X-PAK2 in resting stage VI oocytes, whereas Rac1 is not involved in this regulation. During the process of maturation, X-PAK2 phosphorylation results in its inactivation and allows maturation to proceed to completion. Activation of mitogen-activated protein kinase and cyclin B-p34(cdc2) is coincident with X-PAK2 inactivation, and purified active MPF inhibits X-PAK2, demonstrating the existence of a new positive feedback loop. Our results confirm and extend the importance of p21-activated kinases 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 rearrangements leading to spindle migration and anchorage to the animal pole cortex.
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