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MEN2A-RET-induced cellular transformation by activation of STAT3.

Oncogene | Aug 30, 2001

http://www.ncbi.nlm.nih.gov/pubmed/11536047

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.

Pubmed ID: 11536047 RIS Download

Mesh terms: 3T3 Cells | Animals | Binding Sites | COS Cells | Cell Division | Cell Line | Cell Transformation, Neoplastic | DNA-Binding Proteins | Dose-Response Relationship, Drug | Drosophila Proteins | Enzyme Activation | Genes, Reporter | Humans | Mice | Multiple Endocrine Neoplasia Type 2a | Oncogenes | Phosphorylation | Precipitin Tests | Protein Binding | Protein Structure, Tertiary | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-ret | Receptor Protein-Tyrosine Kinases | STAT3 Transcription Factor | Serine | Time Factors | Trans-Activators | Transcriptional Activation | Transfection | Tyrosine | Up-Regulation