© 2005 The Japanese Biochemical Society
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Preferences for Phosphorylation Sites in the Retinoblastoma Protein of D-Type Cyclin–Dependent Kinases, Cdk4 and Cdk6, In Vitro
1 Banyu Tsukuba Research Institute in collaboration with Merck Research Laboratories, 3 Okubo, Tsukuba, Ibaraki 300-2611; 2 Division of Cellular and Molecular Biology, Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639; 3 Department of Biochemistry 1, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu 431-3192; and 4 Radiobiology Division, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045
To whom correspondence should be addressed. Tel: +81-298-77-2214, Fax: +81-298-77-2027, E-mail: hiroshi_hirai{at}merck.com
ABSTRACT
D-type cyclin–dependent kinases (Cdk4 and Cdk6) regulate the G1 to S phase progression of the mammalian cell cycle. It has been suggested that Cdk4 and Cdk6 may have distinct functions in vivo, even though they are indistinguishable biochemically. Here we show that although these Cdks phosphorylate multiple residues in pRB, they do so with different residue selectivities in vitro; Thr821 and Thr826 are preferentially phosphorylated by Cdk6 and Cdk4, respectively. This raises the possibility different substrate specificities lead to their different roles in the regulation of cellular events. Furthermore, our results indicate the new concept that Cdk itself contributes to substrate recognition.
FOOTNOTES
* Present address: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033.
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