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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.

Pubmed ID: 11536047

Authors

  • Schuringa JJ
  • Wojtachnio K
  • Hagens W
  • Vellenga E
  • Buys CH
  • Hofstra R
  • Kruijer W

Journal

Oncogene

Publication Data

August 30, 2001

Associated Grants

None

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