外域
ADAM10型
金属蛋白酶
去整合素
劈理(地质)
蛋白酶
化学
生物化学
糖蛋白
细胞生物学
细胞外
基质金属蛋白酶
生物
酶
受体
古生物学
断裂(地质)
作者
Franka Scharfenberg,Andreas O. Helbig,Martin Sammel,Julia Benzel,Uwe Schlomann,Florian Peters,Rielana Wichert,Maximilian Bettendorff,Dirk Schmidt-Arras,Stefan Rose‐John,Catherine Moali,Stefan F. Lichtenthaler,Claus U. Pietrzik,Jörg W. Bartsch,Andreas Tholey,Christoph Becker‐Pauly
标识
DOI:10.1007/s00018-019-03184-4
摘要
Disintegrin and metalloproteinases (ADAMs) 10 and 17 can release the extracellular part of a variety of membrane-bound proteins via ectodomain shedding important for many biological functions. So far, substrate identification focused exclusively on membrane-anchored ADAM10 and ADAM17. However, besides known shedding of ADAM10, we identified ADAM8 as a protease capable of releasing the ADAM17 ectodomain. Therefore, we investigated whether the soluble ectodomains of ADAM10/17 (sADAM10/17) exhibit an altered substrate spectrum compared to their membrane-bound counterparts. A mass spectrometry-based N-terminomics approach identified 134 protein cleavage events in total and 45 common substrates for sADAM10/17 within the secretome of murine cardiomyocytes. Analysis of these cleavage sites confirmed previously identified amino acid preferences. Further in vitro studies verified fibronectin, cystatin C, sN-cadherin, PCPE-1 as well as sAPP as direct substrates of sADAM10 and/or sADAM17. Overall, we present the first degradome study for sADAM10/17, thereby introducing a new mode of proteolytic activity within the protease web.
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