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Regulation of STAT3-mediated signaling by LMW-DSP2

Oncogene volume 25, pages 5801–5806 (2006)Cite this article

Abstract

Signal transducer and activator of transcription 3 (STAT3), which mediates biological actions in many physiological processes, is activated by cytokines and growth factors, and has been reported to be constitutively activated in numerous cancer cells. In this study, we examined whether low molecular weight-dual specificity phosphatase two (LMW-DSP2) is involved in the regulation of the interleukin 6 (IL-6)/leukemia inhibitory factor (LIF)/STAT3-mediated signaling pathway. IL-6/LIF-induced LMW-DSP2 expression in murine testicular or hepatoma cell lines, while LMW-DSP2 overexpression in 293T cells suppressed IL-6-induced phosphorylation and activation of STAT3. Furthermore, LMW-DSP2 suppressed the expression of IL-6-induced endogenous genes. In contrast, small-interfering RNA-mediated reduction of LMW-DSP2 expression enhanced IL-6-induced STAT3-dependent transcription. In fact, LMW-DSP2 interacted with STAT3 in vivo and endogenous LMW-DSP2 bound to STAT3 in murine testicular GC-1 cells. These results strongly suggest that LMW-DSP2 acts as a negative regulator of the IL-6/LIF/STAT3-mediated signaling pathway.

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Acknowledgements

This work was supported in part by grants from Japan Rheumatism Foundation and Industrial Technology Research Grant Program in 2005 from New Energy and Industrial Technology Development Organization (NEDO) of Japan.

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Authors and Affiliations

  1. Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan

    Y Sekine, S Tsuji, O Ikeda, N Sato & T Matsuda

  2. Department of Life Sciences, Laboratory of Molecular Food Chemistry and Biochemistry, Faculty of Bioresources, Mie University, 1577 Kuriyamachiya-cho, Tsu, Mie, Japan

    N Aoki

  3. Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-Cho, Chikusa-Ku, Nagoya, Japan

    K Aoyama

  4. Nippon Boehringer Ingelheim Co., Ltd., Kawanishi Pharma Research Institute, 3-10-1 Yato, Kawanishi, Hyogo, Japan

    K Sugiyama

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  1. Y Sekine
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Correspondence to T Matsuda.

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Sekine, Y., Tsuji, S., Ikeda, O. et al. Regulation of STAT3-mediated signaling by LMW-DSP2. Oncogene 25, 5801–5806 (2006). https://doi.org/10.1038/sj.onc.1209578

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