期刊
FEBS LETTERS
卷 588, 期 5, 页码 653-658出版社
WILEY
DOI: 10.1016/j.febslet.2013.12.025
关键词
MET; Small molecule tyrosine kinase inhibitor; Receptor downregulation; CBL; Receptor ubiquitination; MET Tyr1003
资金
- Swiss National Science Foundation [31003A-125394]
- Novartis Stiftung
- Stiftung zur Krebsbekampfung [265]
- Swiss National Science Foundation (SNF) [31003A_125394] Funding Source: Swiss National Science Foundation (SNF)
The MET receptor tyrosine kinase is deregulated primarily via overexpression or point mutations in various human cancers and different strategies for MET inhibition are currently evaluated in clinical trials. We observed by Western blot analysis and by Flow cytometry that MET inhibition by different MET small molecule inhibitors surprisingly increases in a dose-dependent manner total MET levels in treated cells. Mechanistically, this inhibition-related MET accumulation was associated with reduced Tyr1003 phosphorylation and MET physical association with the CBL ubiquitin ligase with concomitant decrease in MET ubiquitination. These data may suggest careful consideration for design of anti-MET clinical protocols. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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