Cdc2-cyclin B triggers H3 kinase activation of Aurora-A in Xenopus oocytes.
Xenopus oocytes are arrested in meiotic prophase I and resume meiotic divisions in response to progesterone. Progesterone triggers activation of M-phase promoting factor (MPF) or Cdc2-cyclin B complex and neosynthesis of Mos kinase, responsible for MAPK activation. Both Cdc2 and MAPK activities are required for the success of meiotic maturation. However, the signaling pathway induced by progesterone and leading to MPF activation is poorly understood, and most of the targets of both Cdc2 and MAPK in the oocyte remain to be determined. Aurora-A is a Ser/Thr kinase involved in separation of centrosomes and in spindle assembly during mitosis. It has been proposed that in Xenopus oocytes Aurora-A could be an early component of the progesterone-transduction pathway, acting through the regulation of Mos synthesis upstream Cdc2 activation. We addressed here the question of Aurora-A regulation during meiotic maturation by using new in vitro and in vivo experimental approaches. We demonstrate that Cdc2 kinase activity is necessary and sufficient to trigger both Aurora-A phosphorylation and kinase activation in Xenopus oocyte. In contrast, these events are independent of the Mos/MAPK pathway. Aurora-A is phosphorylated in vivo at least on three residues that regulate differentially its kinase activity. Therefore, Aurora-A is under the control of Cdc2 in the Xenopus oocyte and could be involved in meiotic spindle establishment.
Maton
Gilliane
G
Laboratoire de Biologie du Développement, Unite Mixte de Recherche-CNRS 7622, Université Pierre et Marie Curie, Boîte 24, 4 Place Jussieu, Paris 75252 cedex 05, France.
Thibier
Catherine
C
Castro
Anna
A
Lorca
Thierry
T
Prigent
Claude
C
Jessus
Catherine
C
D000818:Animals; D064127:Aurora Kinases; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D018797:Cell Cycle Proteins; D000242:Cyclic AMP / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004789:Enzyme Activation; D006657:Histones / Q000378:metabolism*; D007700:Kinetics; D008540:Meiosis; D008938:Mitosis; D009865:Oocytes / Q000201:enzymology; D010455:Peptides / Q000737:chemistry; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011374:Progesterone / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus; D013997:Time Factors; D015854:Up-Regulation; D014981:Xenopus; D029867:Xenopus Proteins; D020687:cdc25 Phosphatases / Q000378:metabolism
D018797:Cell Cycle Proteins; D019926:Cyclin B; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D006657:Histones; D010455:Peptides; D011994:Recombinant Proteins; D029867:Xenopus Proteins; D011374:Progesterone; D000242:Cyclic AMP; D011494:Protein Kinases; C112134:AURKA protein, Xenopus; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D010744:Phosphoric Monoester Hydrolases; D020687:cdc25 Phosphatases