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A role for SHPS-1/SIRPα1 in IL-1β- and TNFα-dependent signaling

Oncogene volume 21, pages 8871–8878 (2002)Cite this article

Abstract

We investigated the role of SHPS-1/SIRPα1 in IL-1β- and TNFα-dependent signaling that leads to the activation of Erk 1/2 and Akt. Treatment of Balb3T3 cells with IL-1β or TNFα activated tyrosine phosphorylation of SHPS-1, its association with SHP-2 and the phosphorylation of Erk 1/2 and Akt. PP1, a specific inhibitor for the Src family protein tyrosine kinases, strongly inhibited tyrosine phosphorylation of SHPS-1 and complex formation of SHPS-1 with SHP-2 by IL-1β. In addition, PP1 substantially inhibited the IL-2β- and TNFα-dependent activation of Erk 1/2 and Akt. Exogenous expression of either SHPS-1 mutants that lack SHP-2 binding function or a dominant negative mutant of SHP-2 markedly inhibited the activation of Erk 1/2 and Akt by IL-1β, whereas wild type SHPS-1 did not. Moreover, IL-1β-stimulation induced association of SHPS-1 with IL-1RAcP, a second subunit of IL-1 receptor, whereas expression of SHPS-1 mutant that lack SHP-2 binding function clearly blocked the association and tyrosine phosphorylation of endogenous SHPS-1. Taken together, our results strongly suggest that activation of Erk 1/2 and Akt by proinflammatory cytokines requires tyrosine phosphorylation of SHPS-1 and subsequent association of SHPS-1 with SHP-2.

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Acknowledgements

We thank members and staff of the Hamaguchi Laboratory for their technical assistance and helpful discussions. This work was supported by a Grant-in-Aid for Center of Excellence (COE) Research from the Ministry of Education, Science, Sports and Culture of Japan, and a grant under the Monbusho International Scientific Research Program.

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Authors and Affiliations

  1. Laboratory of Molecular Pathogenesis, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, 466-8550, Nagoya, Japan

    Ali Reja Mohammad Ruhul Amin, Kazuya Machida, Kumi Oshima, Myat Lin Oo, Aye Aye Thant, Takeshi Senga, Satoru Matsuda & Michinari Hamaguchi

  2. Department of Immunology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, 466-8550, Nagoya, Japan

    Anwarul Azim Akhand

  3. Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi, 570-8506, Japan

    Akito Maeda & Tomohiro Kurosaki

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  1. Ali Reja Mohammad Ruhul Amin
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Correspondence to Michinari Hamaguchi.

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Ruhul Amin, A., Machida, K., Oshima, K. et al. A role for SHPS-1/SIRPα1 in IL-1β- and TNFα-dependent signaling. Oncogene 21, 8871–8878 (2002). https://doi.org/10.1038/sj.onc.1206018

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