title: Regulation of Xenopus p21-activated kinase (X-PAK2) by Cdc42 and maturation-promoting factor controls Xenopus oocyte maturation.
abstract: 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.
authors.affiliation: Centre de Recherche de Biochimie Macromoléculaire, CNRS UPR 1086, 1919 Route de Mende, 34293 Montpellier cedex 5, France.
authors.forename: J
authors.initials: J
authors.lastname: Cau
authors.forename: S
authors.initials: S
authors.lastname: Faure
authors.forename: S
authors.initials: S
authors.lastname: Vigneron
authors.forename: J C
authors.initials: JC
authors.lastname: Labbé
authors.forename: C
authors.initials: C
authors.lastname: Delsert
authors.forename: N
authors.initials: N
authors.lastname: Morin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005260:Female; D005306:Fertilization / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D008969:Molecular Sequence Data; D009865:Oocytes / Q000201:enzymology / Q000254:growth & development*; D011374:Progesterone / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014981:Xenopus; D054462:p21-Activated Kinases
chemical_list: D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D011994:Recombinant Proteins; D011374:Progesterone; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases