Involvement of protein kinase B/AKT in early development of mouse fertilized eggs.
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.
Feng
Chen
C
Department of Biochemical and Molecular Biology, China Medical University, Shenyang 110001, Liaoning, China.
Yu
Aiming
A
Liu
Ying
Y
Zhang
Jie
J
Zong
Zhihong
Z
Su
Wenhui
W
Zhang
Zhe
Z
Yu
Dahai
D
Sun
Qing-Yuan
QY
Yu
Bingzhi
B
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D004247:DNA / Q000235:genetics; D047108:Embryonic Development / Q000502:physiology; D005260:Female; D008297:Male; D016200:Maturation-Promoting Factor / Q000378:metabolism; D000090204:Mesothelin; D051379:Mice / Q000196:embryology*; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D015053:Zygote / Q000201:enzymology* / Q000254:growth & development
C000715528:Msln protein, mouse; D004247:DNA; D051057:Proto-Oncogene Proteins c-akt; D016203:CDC2 Protein Kinase; D016200:Maturation-Promoting Factor; D000090204:Mesothelin