MEN2A-RET-induced cellular transformation by activation of STAT3

Oncogene. 2001 Aug 30;20(38):5350-8. doi: 10.1038/sj.onc.1204715.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Proto-Oncogene Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat3 protein, mouse
  • Trans-Activators
  • Tyrosine
  • Serine
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Ret protein, Drosophila
  • Ret protein, mouse