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Title 

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

 

ETV6-NTRK3 chimeric 타이로신 카이네이스의 TGF-β 2형 수용체 불활성화에 의한 TGF-β 2

Authors 

W JinB C KimC TognonHo Jae LeeS PatelC L LannonJ M MarisT J TricheP H B SorensenS J Kim

Publisher 

National Academy of Sciences

Issue Date 

2005

Citation 

Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 45, pp. 16239-16244

Keywords 

chromosomal translocationcongenital fibrosarcomaTGF-β receptorprotein tyrosine kinasetranscription factor ETV6transforming growth factor beta receptortransforming growth factor beta receptor 2DNA synthesis inhibitionreceptor down regulationactivin receptors, type I

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.

ISSN 

0027-8424

Link 

http://dx.doi.org/10.1073/pnas.0503137102

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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