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Cell cycle start from quiescence controlled by tyrosine phosphorylation of Cdk4

Oncogene volume 18, pages 565–571 (1999)Cite this article

Abstract

In mammals Cdk4 (or Cdk6 in some cell types) is required for starting the cell cycle. Recently we showed that Cdk4 is regulated by tyrosine phosphorylation and dephosphorylation, and that this regulation is required for a DNA damage-induced G1 arrest. We report here that a generic anti-phosphotyrosine antibody can detect tyrosine-phosphorylated Cdk4 and that as revealed by immunoblot detection and kinase assay, this regulation is employed for DNA damage-responsive checkpoint control during cell cycle start from quiescence. In rat fibroblasts traversing G1 or arrested in G1 by deprivation of anchorage, Cdk4 does not undergo tyrosine phosphorylation. Tyrosine phosphorylation occurs only during cell's arrest in quiescence and dephosphorylation during their cell cycle start. Ultraviolet irradiation blocks dephosphorylation and concomitant activation of Cdk4, thereby preventing the start of cell cycling. Thus, unlike tyrosine phosphorylation of Cdc2, which controls phase transition in the regular cell cycle, tyrosine phosphorylation of Cdk4 is employed for controlling cell cycle start from quiescence in a rat fibroblast.

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Acknowledgements

This work was supported by grants from the Department of Science, Education and Culture of Japan and from HFSP.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, 113, Japan

    Shigeki Jinno, Shih-Chieh Hung & Hiroto Okayama

  2. Department of Orthopedic Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, 113, Japan

    Shih-Chieh Hung

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  1. Shigeki Jinno
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  2. Shih-Chieh Hung
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Jinno, S., Hung, SC. & Okayama, H. Cell cycle start from quiescence controlled by tyrosine phosphorylation of Cdk4. Oncogene 18, 565–571 (1999). https://doi.org/10.1038/sj.onc.1202347

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