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  • Title: MEN2A-RET-induced cellular transformation by activation of STAT3.
    Author: Schuringa JJ, Wojtachnio K, Hagens W, Vellenga E, Buys CH, Hofstra R, Kruijer W.
    Journal: Oncogene; 2001 Aug 30; 20(38):5350-8. PubMed ID: 11536047.
    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 STAT3alpha but not STAT3beta, 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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