Identification of ADAM10 as a major TNF sheddase in ADAM17-deficient fibroblasts
Identification of ADAM10 as a major TNF sheddase in ADAM17-deficient fibroblasts
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DOI：
10.1016/j.cyto.2009.03.002
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发表时间：
2009-06-01
期刊：
影响因子：
3.8
通讯作者：
Bereta, Joanna
中科院分区：
文献类型：
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作者：
Mezyk-Kopec, Renata;Bzowska, Monika;Bereta, Joanna
ADAM17(一种去整合素和金属蛋白酶)缺陷的小鼠成纤维细胞稳定地转染前肿瘤坏死因子基因，释放大量具有生物活性的可溶性肿瘤坏死因子。负责这一活性的酶是一种膜蛋白，它能水解人肿瘤坏死因子原中的肽键Ala(76)：Val(77)。它的活性被1，10-菲托林和GM6001抑制，不受TIMP-2(金属蛋白酶组织抑制因子-2)的影响，被离子霉素刺激。这些特征与ADAM10相匹配。ShRNA适度沉默ADAM10可显著抑制肿瘤坏死因子的释放。ADAM10的表达水平与ADAM17活性的存在之间没有相关性。我们的结果表明，在缺乏ADAM17活性的细胞中，ADAM10可能作为肿瘤坏死因子脱氢酶发挥作用。(C)2009爱思唯尔有限公司。保留所有权利。
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.