The ETV6-NTRK3 chimeric tyrosine kinase suppresses TGF-β signaling by inactivating the TGF-β type II receptor

Wook Jin, Byung Chul Kim, Cristina Tognon, Ho Jae Lee, Sejal Patel, Chris L. Lannon, John M. Maris, Timothy J. Triche, Poul H.B. Sorensen, Seong Jin Kim

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

An emerging theme in cancer biology is that although some malignancies occur through the sequential acquisition of different genetic alterations, certain dominantly acting oncoproteins such as those associated with chromosomal translocations have multiple functions and do not require additional mutations for cell transformation. The ETV6-NTRK3 (EN) chimeric tyrosine kinase, a potent oncoprotein expressed in tumors derived from multiple cell lineages, functions as a constitutively active protein tyrosine kinase. Here, we show that EN suppresses TGF-β signaling by directly binding to the type II TGF-β receptor, thereby preventing it from interacting with the type I TGF-β receptor. This activity requires a functional EN protein tyrosine kinase, and type II TGF-β receptor appears to be a direct target of EN. Our findings provide evidence for a previously undescribed mechanism by which oncogenic tyrosine kinases can block TGF-β tumor suppressor activity.

Original languageEnglish (US)
Pages (from-to)16239-16244
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number45
DOIs
StatePublished - Nov 8 2005
Externally publishedYes

Keywords

  • Chromosomal translocation
  • Congenital fibrosarcoma
  • TGF-β receptor

ASJC Scopus subject areas

  • General

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