期刊
CYTOKINE
卷 46, 期 3, 页码 309-315出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2009.03.002
关键词
Ectodomain shedding; ADAM10; ADAM 17; TNF; RNA interference
资金
- Polish Ministry of Science and Higher Education [0118/P01/2006/30, 31441B/P01/2007/33]
ADAM17 (a disintegrin and metalloprotease)-deficient murine fibroblasts stably transfected with proTNF cDNA release significant amounts of biologically active soluble TNF. The enzyme responsible for this activity is a membrane protein that hydrolyzes the peptide bond Ala(76):Val(77) within proTNF. Its activity is inhibited by 1,10-phenantroline and GM6001, insusceptible to TIMP-2 (tissue inhibitor of metalloproteinases-2), and stimulated by ionomycin. These characteristics match ADAM10. The moderate silencing of ADAM10 by shRNA resulted in a significant inhibition of TNF shedding. There was no correlation between the level of ADAM 10 expression and the presence of active ADAM17. Our results indicate that ADAM10 may function as the TNF sheddase in cells which lack ADAM17 activity. (C) 2009 Elsevier Ltd. All rights reserved.
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