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| Original Paper |
| MEN2A-RET-induced cellular transformation by activation of STAT3 |
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| Jan Jacob Schuringa1,2, Katarzyna Wojtachnio1, Werner Hagens1, Edo Vellenga2, Charles HCM Buys3, Robert Hofstra3 and Wiebe Kruijer1 |
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1Department of Developmental Genetics, University of Groningen, Kerklaan 30, 9751 NN, Haren, The Netherlands
2Department of Hematology, University of Groningen, Kerklaan 30, 9751 NN, Haren, The Netherlands
3Department of Medical Genetics, University of Groningen, Kerklaan 30, 9751 NN, Haren, The Netherlands
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Correspondence to: W Kruijer, Department of Developmental Genetics, Biological Centre Haren, Kerklaan 30, 9751 NN, Haren, The Netherlands; E-mail: W.Kruijer@biol.rug.nl
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| 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 STAT3 but not STAT3 , 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. Oncogene (2001) 20, 5350-5358. |
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| Keywords |
| Ret tyrosine kinase receptor; MEN2A; STAT3; cellular transformation |
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| Received 11 April 2001; revised 24 May 2001; accepted 8 June 2001 |
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| 30 August 2001, Volume 20, Number 38, Pages 5350-5358 |
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