The 14‐3‐3 protein binds its target proteins with a common site located towards the C‐terminus

FEBS Letters

Ichimura, Tohru¹  Omata, Saburo¹  Horigome, Tsuneyosi¹  Ohno, Shigeo²  Takahashi, Masuhiro⁴  Isobe, Toshiaki³  Itagaki, Chiharu¹  Ito, Mitsuki¹ 

[1] Department of Biochemistry, Faculty of Science, Niigata University, Niigata 950-21, Japan;Department of Molecular Biology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama 236, Japan;Laboratory of Biochemistry, Graduate School of Science, Tokyo Metropolitan University, Hachioji-shi, Tokyo 192-03, Japan;Department of Medical Technology, College of Biomedical Technology, Niigata University, Niigata 951, Japan

关键词: Signal transduction;    Phosphorylation;    14-3-3 protein;    Oncogene;    Protein structure;    TPH;    tryptophan hydroxylase;    TH;    tyrosine hydroxylase;    CaM;    calmodulin;    GST;    glutathione-S-transferase;    SDS;    sodium dodecylsulfate;    PAGE;    polyacrylamide gel electrophoresis;    2D;    two-dimensional;   

DOI  :  10.1016/S0014-5793(97)00910-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The 14-3-3 protein family binds a variety of proteins in cell-signaling pathways, but the structural elements necessary for the ligand binding are poorly understood. Here we demonstrate that the `box-1' region, which spans residues 171–213 in the η-isoform and was previously identified as the binding site of 14-3-3 to the phosphorylated tryptophan hydroxylase, plays a critical role in the interaction with many target proteins. Using a series of truncated 14-3-3 mutants, we show that the mutant 167–213 carrying box-1 binds bacurovirus-expressed Raf-1 and Bcr protein kinases to the similar extent as the full-length 14-3-3 in a phosphorylation-dependent manner, while the mutants lacking this region abolish the binding activity. Furthermore, the box-1 region also appears essential for binding of 14-3-3 to more than 40 phosphoproteins found in the brainstem extract. These results suggest that the box-1 region, consisting of helices 7 and 8 in the tertiary structure, is a common structural element whereby the 14-3-3 protein binds many, if not all, target proteins.

【 授权许可】

Unknown