MEN2A-RET-induced cellular transformation by activation of STAT3.
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.
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
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
Oncogene
Date: Aug. 30, 2001
PubMed ID: 11536047
View in: Pubmed Google Scholar
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