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Department of Biochemical and Molecular Biology,3 China Medical University, Shenyang 110001, Liaoning, China
Institute of Zoology,4 Chinese Academy of Sciences, Beijing 100080, China
ABSTRACT
The activation of AKT (also called protein kinase B) is thought to be a critical step in the phosphoinositide 3-kinase pathway that regulates cell growth and differentiation. In this report, we investigated the role of AKT in the regulation of mouse early embryo development. Injection of mRNA coding for a constitutively active myristoylated AKT (myr-Akt1) into one-cell stage fertilized eggs induced cell division more effectively than injection of wild-type AKT (Akt1-WT) mRNA, whereas microinjection of mRNA of kinase-deficient AKT (Akt1-KD) delayed the first mitotic division. Meanwhile, microinjection of different kinds of mRNA of AKT affected the phosphorylation status of CDC2A-Tyr15 and the activation of M-phase promoting factor (MPF). To investigate the intermediate factor between AKT and MPF, we then injected one-cell stage eggs first with Akt1-WT mRNA or myr-Akt1 mRNA and then with mRNA encoding either wild-type CDC25B (Cdc25b-WT) or a AKT-nonphosphorylatable Ser351 to Ala CDC25B mutant (Cdc25b-S351A). Cdc25b-S351A strongly inhibited the effect of AKT. Therefore, AKT causes the activation of MPF and strongly promotes the development of one-cell stage mouse fertilized eggs by inducing AKT-dependent phosphorylation of CDC25B, a member of the CDC25 phosphatase family. Our finding that CDC25B acts as a potential target of AKT provides new insight into the effect of AKT in the regulation of early development of mouse embryos.
AKT, CDC25B, early development, embryo, kinases, mouse, M-phase promoting factor, signal transduction
1Sponsored by the National Nature Science Foundation of China (30570945).
Correspondence: 2Bingzhi Yu, Department of Biochemical and Molecular Biology, China Medical University, Beier Road, Heping District, Shenyang 110001, Liaoning Province, China. FAX: 0086 24 23261253; e-mail address: ybzbiochem{at}yeah.net
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