한빛사 논문
NIH / NCI
Abstract
*Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-5055; Division of Life Sciences, Kangwon National University, Chuncheon 200-701, Korea; Department of Pathology, British Columbia\''s Children\''s Hospital, Vancouver, BC, Canada V6H 3V4; ¶Korea Research Institute of Bioscience and Biotechnology, Daejon 305-806, Korea; ||Division of Oncology, Children\''s Hospital of Philadelphia, Department of Pediatrics and Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; and Children\''s Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA 90033
Edited by Peter K. Vogt, The Scripps Research Institute, La Jolla, CA, and approved September 15, 2005 (received for review April 15, 2005)
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- signaling by directly binding to the type II TGF- receptor, thereby preventing it from interacting with the type I TGF- receptor. This activity requires a functional EN protein tyrosine kinase, and type II TGF- 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- tumor suppressor activity.
Author contributions: P.H.B.S. and S.-J.K. designed research, analyzed data, and wrote the paper; W.J., B.-C.K., C.T., H.-J.L., and S.P. performed research; and C.L.L., J.M.M., and T.J.T. contributed new reagents/analytic tools.
Conflict of interest statement: No conflicts declared.
**To whom correspondence may be addressed.
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