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  • Original Paper
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The transmembrane protein tyrosine phosphatase RPTPσ modulates signaling of the epidermal growth factor receptor in A431 cells

Oncogene volume 18, pages 4069–4079 (1999)Cite this article

Abstract

Attenuation of epidermal growth factor receptor signaling by the ganglioside GM3 has previously been found to involve activation of an unknown protein-tyrosine phosphatase (PTP). In transient expression experiments we tested different PTPs for activation towards EGF receptor by GM3. The transmembrane PTP RPTPσ but not RPTPα or the SH2-domain PTP SHP-1 exhibited elevated activity towards EGF receptor in GM3-treated cells. The possible relevance of RPTPσ for regulation of EGF receptor signaling activity was further explored in stable A431 cells lines inducibly expressing RPTPσ or RPTPσ antisense RNA. RPTPσ expression clearly reduced EGF receptor phosphorylation. Also, soft agar colony formation of respective cell lines was reduced upon RPTPσ expression whereas RPTPσ antisense RNA expression augmented both, EGF receptor phosphorylation and soft agar colony formation. In addition, RPTPσ antisense RNA expression rendered A431 cells resistant to inhibition of EGF receptor phosphorylation by GM3. We propose that RPTPσ participates in EGF receptor dephosphorylation in A431 cells, becomes activated by GM3 via an unknown mechanism and is thereby capable to mediate attenuation of EGF receptor phosphorylation by GM3.

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Acknowledgements

We are grateful to Dr A Ullrich for the generous provision of EGF receptor and SHP-1 cDNAs and for antibody 322, Dr ML Thomas for providing the RPTPα cDNA, Dr A Luckenbach for antibody 425 and Dr H Bujard for the tetracycline expression system. We thank also Dr J Clement for help with RT – PCR experiments. This work was supported by Sonderforschungsbereich 197 of the Deutsche Forschungsgemeinschaft (project A9) and by a grant from the Max-Planck-Society (to F-D Böhmer). E Suárez Pestana was recipient of a scholarship from the Max-Planck-Society.

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  1. Research Unit `Molecular Cell Biology', Klinikum der Friedrich-Schiller Universität Jena, Drackendorfer Str.1, Jena, D-07747, Germany

    Eduardo Suárez Pestana, Tencho Tenev, Steffen Groß, Borislav Stoyanov & Frank-D Böhmer

  2. Department of Oncology, Biomedical Research Center, Osaka University Medical School, 2-2, Yamadaoka, Osaka, 565, Suita, Japan

    Masato Ogata

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  1. Eduardo Suárez Pestana
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Pestana, E., Tenev, T., Groß, S. et al. The transmembrane protein tyrosine phosphatase RPTPσ modulates signaling of the epidermal growth factor receptor in A431 cells. Oncogene 18, 4069–4079 (1999). https://doi.org/10.1038/sj.onc.1202794

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