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v-Src suppresses SHPS-1 expression via the Ras-MAP kinase pathway to promote the oncogenic growth of cells

Oncogene volume 19, pages 1710–1718 (2000)Cite this article

Abstract

We investigated the effect of cell transformation by v-src on the expression and tyrosine phosphorylation of SHPS-1, a putative docking protein for SHP-1 and SHP-2. We found that transformation by v-src virtually inhibited the SHPS-1 expression at mRNA level. While nontransforming Src kinases including c-Src, nonmyristoylated forms of v-Src had no inhibitory effect on SHPS-1 expression, transforming Src kinases including wild-type v-Src and chimeric mutant of c-Src bearing v-Src SH3 substantially suppressed the SHPS-1 expression. In cells expressing temperature sensitive mutant of v-Src, suppression of the SHPS-1 expression was temperature-dependent. In contrast, tyrosine phosphorylation of SHPS-1 was rather activated in cells expressing c-Src or nonmyristoylated forms of v-Src. SHPS-1 expression in SR3Y1 was restored by treatment with herbimycin A, a potent inhibitor of tyrosine kinase, or by the expression of dominant negative form of Ras. Contrary, active form of Mek1 markedly suppressed SHPS-1 expression. Finally, overexpression of SHPS-1 in SR3Y1 led to the drastic reduction of anchorage independent growth of the cells. Taken together, our results suggest that the suppression of SHPS-1 expression is a pivotal event for cell transformation by v-src, and the Ras-MAP kinase cascade plays a critical role in the suppression.

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Acknowledgements

We are greatly indebted to Hidesaburo Hanafusa for his continuous encouragement and support. We thank Lary A Feig for his gift of S17N ras, Fumiko Yamauchi for her excellent technical assistance. This work was supported by a Grant-in-Aid for COE Research from the Ministry of Education, Science and Culture of Japan, a Grant under the Monbusho International Scientific Research Program.

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Authors and Affiliations

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

    Kazuya Machida, Satoru Matsuda, Takeshi Senga, Aye Aye Thant, Hisashi Kurata, Kou Miyazaki, Kazuhiko Hayashi, Takahito Okuda & Michinari Hamaguchi

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

    Kazuya Machida, Kenichi Yamaki, Kazuhiko Hayashi & Tetsuo Hayakawa

  3. Department of Internal Medicine III, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, 466-8550, Nagoya, Japan

    Hisashi Kurata

  4. Department of Surgery I, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, 466-8550, Nagoya, Japan

    Kou Miyazaki

  5. Department of Hematopoietic Factors, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-0071, Tokyo, Japan

    Toshio Kitamura

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Machida, K., Matsuda, S., Yamaki, K. et al. v-Src suppresses SHPS-1 expression via the Ras-MAP kinase pathway to promote the oncogenic growth of cells. Oncogene 19, 1710–1718 (2000). https://doi.org/10.1038/sj.onc.1203497

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