Possible involvement of mitogen- and stress-activated protein kinase 1, MSK1, in metaphase-II arrest through phosphorylation of EMI2 in mouse oocytes.
Possible involvement of mitogen- and stress-activated protein kinase 1, MSK1, in metaphase-II arrest through phosphorylation of EMI2 in mouse oocytes.
复制标题
DOI：
10.1016/j.ydbio.2011.08.021
复制
发表时间：
2011-11
影响因子：
2.7
通讯作者：
Yu Miyagaki;Yoshinori Kanemori;T. Baba
中科院分区：
文献类型：
--
作者：
Yu Miyagaki;Yoshinori Kanemori;T. Baba
排卵的卵母细胞在第二次减数分裂中期被阻滞。位于Mos-MAPK通路下游的RSK调控非洲爪蟾卵母细胞的中期-II停滞。在小鼠中，除RSK外的其他激酶可能导致中期II停滞，因为RSK 1/RSK 2/RSK 3三重敲除小鼠没有表现出明显的表型。在这里，我们显示的亚细胞定位和可能的作用，有丝分裂原和应激激活激酶1，MSK 1被称为另一个下游激酶的Mos-MAPK途径，在小鼠卵母细胞。免疫组化分析表明，MSK 1存在于生殖囊泡（GV）和细胞质的卵母细胞在GV和中期II阶段，分别。一个活跃的，磷酸化形式的MSK 1主要定位于中期-II纺锤体。对MSK 1活性的抑制未能维持中期II平板内的姐妹染色单体排列。重要的是，MSK 1表现出磷酸化减数分裂细胞周期调节因子EMI 2的四个Ser/Thr残基的能力。磷酸化是卵母细胞中EMI 2活性上调所必需的。这些结果表明，小鼠MSK 1可能通过磷酸化EMI 2在中期II阻滞中发挥关键作用。
Ovulated oocytes are arrested at the metaphase of second meiotic division. The metaphase-II arrest in Xenopus oocytes is regulated by RSKs located downstream of the Mos–MAPK pathway. In mice, other kinase(s) besides RSKs may be responsible for the metaphase-II arrest, because RSK1/RSK2/RSK3-triple knockout mice exhibit no obvious phenotype. Here, we show the subcellular localization and possible role of mitogen- and stress-activated kinase 1, MSK1 known as another downstream kinase of the Mos–MAPK pathway, in the mouse oocytes. Immunostaining analysis indicated that MSK1 is present in the germinal vesicle (GV) and cytoplasm of oocytes at the GV and metaphase-II stages, respectively. An active, phosphorylated form of MSK1 was predominantly localized to the metaphase-II spindle. The inhibition of the MSK1 activity failed to maintain the sister chromatid alignment within the metaphase-II plate. Importantly, MSK1 exhibited the ability to phosphorylate four Ser/Thr residues of meiotic cell-cycle regulator EMI2. The phosphorylation was required for up-regulation of the EMI2 activity in the oocytes. These results suggest that mouse MSK1 may play a key role in the metaphase-II arrest through phosphorylation of EMI2.