Cutting Edge: The Metalloproteinase ADAM17/TNF-α-Converting Enzyme Regulates Proteolytic Shedding of the MHC Class I-Related Chain B Protein1
Cutting Edge: The Metalloproteinase ADAM17/TNF-α-Converting Enzyme Regulates Proteolytic Shedding of the MHC Class I-Related Chain B Protein1
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前沿：金属蛋白酶 ADAM17/TNF-α 转换酶调节 MHC I 类相关链 B 蛋白的蛋白水解脱落1
作者：
P. Boutet;Sonia Agüera;S. Atkinson;C. Pennington;D. Edwards;G. Murphy;H. Reyburn;M. Valés
MHC i类相关链（MIC） A/B是病理状态下表达的跨膜蛋白，是细胞毒性淋巴细胞上发现的激活受体NKG2D的配体。可溶性NKG2D配体在多种类型癌症患者的血清中检测到，它们与受体表达水平降低和NK和ctl功能受损有关。在这项研究中，我们报道了一个金属蛋白酶参与MIC的切割过程的鉴定；抑制和敲低ADAM17/TACE可阻断这些蛋白的脱落。引人注目的是，酶和底物在耐洗涤剂膜微域的招募对于有效的蛋白质水解至关重要。这些发现为MIC脱落的分子机制提供了新的见解。
MHC class I-related chain (MIC) A/B are transmembrane proteins expressed in pathological conditions that are ligands for the activating receptor NKG2D found on cytotoxic lymphocytes. Soluble NKG2D ligands are detected in sera of patients suffering from multiple types of cancer where they are associated with reduced levels of receptor expression and compromised function of NK and CTLs. In this study, we report the identification of a metalloproteinase involved in the cleavage process of MIC; inhibition and knockdown of ADAM17/TACE blocks the shedding of these proteins. Strikingly, the recruitment of both enzyme and substrate to detergent-resistant membrane microdomains is crucial for efficient proteolysis. These findings provide a novel insight into the molecular mechanisms of MIC shedding.
DOI：
10.1172/jci22206
发表时间：
2004-08
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Jennifer D. Wu;L. M. Higgins;A. Steinle;D. Cosman;K. Haugk;S. Plymate
通讯作者：
Jennifer D. Wu;L. M. Higgins;A. Steinle;D. Cosman;K. Haugk;S. Plymate