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MEN2A-RET-induced cellular transformation by activation of STAT3

Oncogene volume 20, pages 5350–5358 (2001)Cite this article

Abstract

The MEN2A oncogene encodes for a constitutive active member of the RET receptor tyrosine kinase family. Here, we report that MEN2A-RET activates Signal Transducer and Activator of Transcription 3 (STAT3) via two YxxV/Q STAT3 docking sites, Tyr752 and Tyr928. MEN2A-RET induces both Tyr705 and Ser727 phosphorylation of STAT3, and STAT3 serine phosphorylation is required for its maximal transcriptional activity. Stable NIH3T3 cell lines expressing both MEN2A-RET and STAT3α but not STAT3β, are characterized by enhanced proliferation and cyclin-D1 promoter activity, and enhanced growth in soft agar. These data indicate that malignant cell growth induced by MEN2A-RET involves its activation of STAT3.

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Acknowledgements

This work was supported by grants from the Dutch Cancer Foundation (RUG 96-1217) and RUG 00-2316).

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Authors and Affiliations

  1. Department of Developmental Genetics, University of Groningen, Kerklaan 30, Haren, 9751 NN, The Netherlands

    Jan Jacob Schuringa, Katarzyna Wojtachnio, Werner Hagens & Wiebe Kruijer

  2. Department of Hematology, University of Groningen, Kerklaan 30, Haren, 9751 NN, The Netherlands

    Jan Jacob Schuringa & Edo Vellenga

  3. Department of Medical Genetics, University of Groningen, Kerklaan 30, Haren, 9751 NN, The Netherlands

    Charles HCM Buys & Robert Hofstra

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  1. Jan Jacob Schuringa
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  2. Katarzyna Wojtachnio
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Correspondence to Wiebe Kruijer.

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Schuringa, J., Wojtachnio, K., Hagens, W. et al. MEN2A-RET-induced cellular transformation by activation of STAT3. Oncogene 20, 5350–5358 (2001). https://doi.org/10.1038/sj.onc.1204715

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