Tyrosine phosphorylation is crucial for growth signaling by tissue inhibitors of metalloproteinases (TIMP‐1 and TIMP‐2)

FEBS Letters

Shinagawa, Akira¹  Hayakawa, Taro²  Yamashita, Kyoko²  Koike, Teruhiko⁴  Noguchi, Toshihide³  Hamaguchi, Michinari⁴  Suzuki, Mitsunori³  Iwata, Hiroyuki⁵ 

[1] Biopharmaceutical Department, Fuji Chemical Industries, Ltd., Takaoka, Toyama 933, Japan;Department of Biochemistry, School of Dentistry, Aichi-Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464, Japan;Department of Periodontology, School of Dentistry, Aichi-Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464, Japan;Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Showa-ku, Nagoya 466, Japan;Isotope Center Medical Research Division, Nagoya University School of Medicine, Showa-ku, Nagoya 466, Japan

关键词: Tissue inhibitor of metalloproteinase;    Cell growth factor;    Tyrosine kinase;    Mitogen-activated protein (MAP) kinase;    MG-63 cell;    TIMP;    tissue inhibitor of metalloproteinases;    [3H]TdR;    [3H]thymidine;    PTYR;    phosphotyrosine;    MAP kinase;    mitogen-activated protein kinase;    D-MEM;    Dulbecco's modified Eagle's minimal essential medium;    FCS;    fetal calf serum;    ERK;    extracellular-signal-regulated protein kinase;   

DOI  :  10.1016/0014-5793(96)01066-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

[³H]Thymidine (TdR) incorporation by human osteosarcoma cell line MG-63 was significantly stimulated at as early as 3 h after the addition of either TIMP-1 or TIMP-2 alone. Maximum stimulation was attained at a concentration of either 20 ng/ml (0.71 nM) TIMP-1 or 1.0 ng/ml (46 pM) TIMP-2. Tyrosine kinase inhibitors such as genistein, erbstatin, and herbimycin A almost completely inhibited the [³H]TdR incorporation stimulated by either of the TIMPs. However, essentially no effect was observed with H-89, H-7, bisindolylmaleimide and K-252a. These inhibition studies suggest a crucial role for tyrosine kinase in the signal transduction of TIMPs. Phosphotyrosine-containing proteins were significantly elevated by the treatment with both TIMPs. We also found that either TIMP stimulated an increase in mitogen-activated protein (MAP) kinase activity, suggesting that MAP kinase plays a role in TIMP-dependent growth signaling.

【 授权许可】

Unknown