New pathways from PKA to the Cdc2/cyclin B complex in oocytes: Wee1B as a potential PKA substrate.
During the growth of the ovarian follicle, mammalian oocytes are arrested in the late G2 phase of meiosis through ill-defined mechanisms until shortly before ovulation. The molecular machinery controlling the meiotic, as well as mitotic, cell cycle is centered around the regulation of the activity of MPF, a complex composed of a catalytic Cdc2 and the cyclin B regulatory subunit. Cdc2 kinase is inactive as long as oocytes remain in a germinal vesicle state. Its activation is the molecular event that triggers germinal vesicle breakdown and oocyte reentry into the cell cycle. Countless studies have indicated that levels of the second messenger cAMP in the oocyte play a critical role in maintaining meiotic arrest. High cyclic AMP levels in the oocyte maintain protein kinase A (PKA) in an active/dissociated state, which in turn leads to the phosphorylation of unknown protein substrates. The biochemical steps linking a decrease in cAMP levels and MPF activation have been explored only recently. Here we will review the data supporting a simple scenario whereby Cdc25 and Wee1 kinase are substrates of the PKA in oocytes. As as result of these regulatory loops, the Cdc2/cyclin B complex is maintained in an inactive state by the two-way PKA-dependent activation of Wee1 and inactivation of Cdc25.
Han
Seung Jin
SJ
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305, USA.
Conti
Marco
M
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism*; D005260:Female; D008540:Meiosis; D000090204:Mesothelin; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism*; D006080:Ovarian Follicle / Q000502:physiology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013045:Species Specificity; D014981:Xenopus; D029867:Xenopus Proteins / Q000378:metabolism*; D020687:cdc25 Phosphatases / Q000378:metabolism
D018797:Cell Cycle Proteins; D019926:Cyclin B; C000715528:Msln protein, mouse; D009687:Nuclear Proteins; D029867:Xenopus Proteins; C530005:WEE1 protein, Xenopus; C466028:Wee2 protein, Xenopus; D011505:Protein-Tyrosine Kinases; C499348:Wee1 protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases; D016203:CDC2 Protein Kinase; D020687:cdc25 Phosphatases; D000090204:Mesothelin