Protein Tyrosine Kinase Wee1B is Essential for Metaphase II Exit in Mouse Oocytes

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Science  31 Mar 2011:
DOI: 10.1126/science.1199211


Waves of cyclin synthesis and degradation regulate the activity of Cdc2 protein kinase during the cell cycle. Cdc2 inactivation by Wee1B-mediated phosphorylation is necessary for arrest of the oocyte at G2-prophase, but it is unclear whether this regulation functions later during the metaphase to anaphase transition. We show that reactivation of a Wee1B pathway triggers the decrease in Cdc2 activity during egg activation. When Wee1B is downregulated, oocytes fail to form a pronucleus in response to Ca2+ signals. Calcium-calmodulin–dependent kinase II (CaMKII) activates Wee1B, and CaMKII-driven exit from metaphase II (MII) is inhibited by Wee1B downregulation, demonstrating that exit from metaphase requires not only a proteolytic degradation of cyclin B, but also the inhibitory phosphorylation of Cdc2 by Wee1B.