文章基本信息

标题：Arg-Ser-775, 792 and 823 in Spacer Region of ADAMTS-18 Is Critical for Thrombin Cleavage
本地全文：下载
作者：Jian Tang 1 , Wei Huang 1 , Ning Shen 1 , Tao Hong 2 , Suying Dang 3* , Wei Zhang 1,2,
期刊名称：Health
印刷版ISSN：1949-4998
电子版ISSN：1949-5005
出版年度：2014
卷号：06
期号：18
页码：2490-2498
DOI：10.4236/health.2014.618286
语种：English
出版社：Scientific Research Publishing
摘要：Cleavage of ADAMTS-18 by thrombin represents a new mechanism of platelet thrombus clearance via the release of active ~45-kDa C-terminal fragments that induces oxidative platelet fragmentation. The exact cleavage sites remain unclear, but Arg (R)775/Ser (S)776 in spacer region of ADAMTS-18 has been shown to be one of the cleavage sites of thrombin. Here, we demonstrate that R792/S793 and R823/S824 are also thrombin cleavage sites by sequence analysis, amino acid mutation and mass spectrometry assay. All these cleavage sites are thrombin-specific and insensitive to other enzymes tested (e.g. cathepsin D or trypsin). Simultaneous mutation of R775, 792, 823 to S775, 792, 823 in ADAMTS-18 completely abrogated the cleavage by thrombin and the generation of active C-terminal 45-kDa fragments. Together with previous study, a total of three thrombin-specific cleavage sites have been identified in spacer region of ADAMTS-18.
关键词：ADAMTS-18; Thrombin; Cleavage; Mass Spectrum