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Akt inhibits Myt1 in the signalling pathway that leads to meiotic G2/M-phase transition

Nature Cell Biology volume 4, pages 111–116 (2002)Cite this article

Abstract

In eukaryotes, entry into M-phase of the cell cycle is induced by activation of cyclin B–Cdc2 kinase. At G2-phase, the activity of its inactivator, a member of the Wee1 family of protein kinases, exceeds that of its activator, Cdc25C phosphatase. However, at M-phase entry the situation is reversed, such that the activity of Cdc25C exceeds that of the Wee1 family. The mechanism of this reversal is unclear. Here we show that in oocytes from the starfish Asterina pectinifera, the kinase Akt (or protein kinase B (PKB)) phosphorylates and downregulates Myt1, a member of the Wee1 family. This switches the balance of regulator activities and causes the initial activation of cyclin B–Cdc2 at the meiotic G2/M-phase transition. These findings identify Myt1 as a new target of Akt, and demonstrate that Akt functions as an M-phase initiator.

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Figure 1: Myt1 is downregulated at meiotic G2/M-phase transition in the absence of cyclin B–Cdc2 activation.
Figure 2: Myt1 inactivation occurs before p90rsk activation at the meiotic G2/M-phase transition.
Figure 3: Akt activation is necessary and sufficient to induce meiotic G2/M-phase transition.
Figure 4: Phosphorylation of Myt1 at Ser 75 by Akt is required for meiotic G2/M-phase transition.
Figure 5: Myt1 is downregulated directly by Akt.
Figure 6: A model for the initiation of the meiotic G2/M-phase transition in Asterina oocytes.

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Acknowledgements

We thank K. Ohsumi, S. Hisanaga and T. Saito for suggestions, L. A. Jaffe and M. Terasaki for critical reading of the manuscript and particularly Y. Kaziro of Shelling-Plau Laboratory of Molecular Medical Science for initiating this study. This work was supported by grants from the Ministry of Education, Science and Culture, Japan, the Human Frontier Science Program, and the Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Corporation to T.K.

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  1. Laboratory of Cell and Developmental Biology, Graduate School of Bioscience, Tokyo Institute of Technology, Nagatsuta, Midoriku, 226-8501, Yokohama, Japan

    Eiichi Okumura, Takeshi Fukuhara, Hitoshi Yoshida, Shin-ichiro Hanada, Rie Kozutsumi, Masashi Mori, Kazunori Tachibana & Takeo Kishimoto

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Correspondence to Takeo Kishimoto.

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Okumura, E., Fukuhara, T., Yoshida, H. et al. Akt inhibits Myt1 in the signalling pathway that leads to meiotic G2/M-phase transition. Nat Cell Biol 4, 111–116 (2002). https://doi.org/10.1038/ncb741

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