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

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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
Author(s)
W Jin; B C Kim; C Tognon; Ho Jae Lee; S Patel; C L Lannon; J M Maris; T J Triche; P H B Sorensen; S J Kim
Bibliographic Citation
Proceedings of National Academy of Sciences of United States of America, vol. 102, no. 45, pp. 16239-16244
Publication Year
2005
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.
Keyword
chromosomal translocationcongenital fibrosarcomaTGF-β receptor
ISSN
0027-8424
Publisher
Natl Acad Sciences
DOI
http://dx.doi.org/10.1073/pnas.0503137102
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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