Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA 94143-0556, USA.
Science. 2011 Apr 22;332(6028):462-5. doi: 10.1126/science.1199211. Epub 2011 Mar 31.
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 down-regulated, oocytes fail to form a pronucleus in response to Ca(2+) signals. Calcium-calmodulin-dependent kinase II (CaMKII) activates Wee1B, and CaMKII-driven exit from metaphase II is inhibited by Wee1B down-regulation, demonstrating that exit from metaphase requires not only a proteolytic degradation of cyclin B but also the inhibitory phosphorylation of Cdc2 by Wee1B.
细胞周期中，细胞周期蛋白的合成和降解波调节 Cdc2 蛋白激酶的活性。Wee1B 介导的磷酸化使 Cdc2 失活，对于卵母细胞在 G2-前期的阻滞是必需的，但尚不清楚这种调节是否在中期到后期的转变过程中发挥作用。我们表明，Wee1B 途径的再激活触发卵母细胞激活过程中 Cdc2 活性的降低。当 Wee1B 下调时，卵母细胞不能对 Ca(2+)信号做出反应形成原核。钙调蛋白依赖性激酶 II (CaMKII) 激活 Wee1B，而 CaMKII 驱动的从中期 II 期的退出被 Wee1B 的下调所抑制，表明从中期退出不仅需要 cyclin B 的蛋白水解降解，还需要 Wee1B 对 Cdc2 的抑制性磷酸化。
