© 2006 The Japanese Biochemical Society.
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Amino Acids C-Terminal to the 14-3-3 Binding Motif in CDC25B Affect the Efficiency of 14-3-3 Binding
1 Division of Life Science and 2 Division of Environmental Science and Engineering, Graduate School of Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192; 3 Biochemistry Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045; 4 Division of Intractable Disease, International Medical Center of Japan, 21-1 Toyama 1-chome, Shinjyuku-ku, Tokyo 162-8655; and 5 Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-0934
* To whom correspondence should be addressed at the present address: Department of Environmental Biochemistry, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kodo, Kyotanabe 610-0395. Tel: +81 76 264 5809, Fax: +81 76 264 5989, E-mail: katsumi{at}kenroku.kanazawa-u.ac.jp
The phospho-site adapter protein 14-3-3 binds to target proteins at amino acid sequences matching the consensus motif Arg-X-X-Ser/Thr-X-Pro, where the serine or threonine residue is phosphorylated and X is any amino acid. The dual-specificity phosphatase CDC25B, which is involved in cell cycle regulation, contains five 14-3-3 binding motifs, but 14-3-3 preferentially binds to the motif at Ser309 in CDC25B1 (or Ser323 in CDC25B3). In the present study, we demonstrate that amino acid residues C-terminal to the 14-3-3 binding motif strongly affect the efficiency of 14-3-3 binding. Alanine substitutions at residues downstream of the Ser309 motif dramatically reduced 14-3-3 binding, although phosphorylation of Ser309 was unaffected. We also observed that binding of endogenous 14-3-3 to mutant CDC25B occurred less efficiently than to the wild type. Mutants to which 14-3-3 cannot bind efficiently tend to be located in the nucleus, although not as specifically as the alanine substitution mutant of Ser309. These results indicate that amino acid sequences C-terminal to the consensus binding site have an important role in the efficient binding of 14-3-3 to at least CDC25B, which may partly explain why some consensus sequences are inactive as 14-3-3 binding sites.
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