Mallen-St Clair Jon, Shi Guo-Ping, Sutherland Rachel E, Chapman Harold A, Caughey George H, Wolters Paul J
Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0111, USA.
Biol Chem. 2006 Aug;387(8):1143-6. doi: 10.1515/BC.2006.141.
The cysteine protease dipeptidyl peptidase I (DPPI) activates granule-associated immune-cell serine proteases. The in vivo activator of DPPI itself is unknown; however, cathepsins L and S are candidates because they activate pro-DPPI in vitro. In this study, we tested whether cathepsins L and S activate pro-DPPI in vivo by characterizing DPPI activity and processing in cells lacking cathepsins L and S. DPPI activity, and the relative size and amounts of DPPI heavy and light chains, were identical in mast cells from wild-type and cathepsin L/S double-null mice. Furthermore, the activity of DPPI-dependent chymase was preserved in tissues of cathepsin L/S double-null mice. These results show that neither cathepsin L nor S is required for activation of DPPI and suggest that one or more additional proteases is responsible.
半胱氨酸蛋白酶二肽基肽酶I（DPPI）可激活颗粒相关的免疫细胞丝氨酸蛋白酶。DPPI自身的体内激活剂尚不清楚；然而，组织蛋白酶L和S是候选者，因为它们在体外可激活前DPPI。在本研究中，我们通过表征缺乏组织蛋白酶L和S的细胞中的DPPI活性及加工过程，来测试组织蛋白酶L和S是否在体内激活前DPPI。野生型和组织蛋白酶L/S双敲除小鼠肥大细胞中的DPPI活性以及DPPI重链和轻链的相对大小及数量是相同的。此外，组织蛋白酶L/S双敲除小鼠组织中DPPI依赖性糜蛋白酶的活性得以保留。这些结果表明，DPPI的激活既不需要组织蛋白酶L也不需要组织蛋白酶S，并提示一种或多种其他蛋白酶起作用。
