MT1 - 基质金属蛋白酶的脱落涉及一种解聚素和金属蛋白酶结构域蛋白（ADAM），且与其在脂筏中的定位无关。

MT1-MMP shedding involves an ADAM and is independent of its localization in lipid rafts.

作者信息

Toth Marta, Sohail Anjum, Mobashery Shahriar, Fridman Rafael

机构信息

Department of Chemistry and Biochemistry and the Walther Cancer Research Center, University of Notre Dame, Notre Dame, IN 46556, USA.

出版信息

Biochem Biophys Res Commun. 2006 Nov 17;350(2):377-84. doi: 10.1016/j.bbrc.2006.09.052. Epub 2006 Sep 22.

DOI:10.1016/j.bbrc.2006.09.052

PMID:17007816

Abstract

The membrane type 1-matrix metalloproteinase (MT1-MMP) is a membrane-anchored protease that its entire ectodomain is shed from the cell surface. Here we show that in HT1080 cells MT1-MMP is shed as two soluble forms of approximately 52 and approximately 50kDa. Analyses in purified HT1080 plasma membranes show that release of these species is a two-step time-dependent process that is mediated by integral membrane metalloprotease(s). Differential sensitivity to TIMP-3 inhibition of the shedding process suggests that the second cleavage step leading to the formation of the 50-kDa soluble species is mediated by an ADAM. We also show that shedding of MT1-MMP is independent of its partition into lipid rafts because both wild type and glycosylphosphatidylinositol (GPI)-anchored MT1-MMP are shed. These studies provide new insights into the process of MT1-MMP ectodomain shedding, which may regulate pericellular proteolysis.

摘要

膜型1基质金属蛋白酶（MT1-MMP）是一种膜锚定蛋白酶，其整个胞外结构域会从细胞表面脱落。在此我们表明，在HT1080细胞中，MT1-MMP以两种可溶性形式脱落，分子量分别约为52 kDa和约50 kDa。对纯化的HT1080质膜的分析表明，这些形式的释放是一个两步的时间依赖性过程，由整合膜金属蛋白酶介导。对脱落过程中TIMP-3抑制的不同敏感性表明，导致形成50 kDa可溶性形式的第二步切割是由一种ADAM介导的。我们还表明，MT1-MMP的脱落与其在脂筏中的分配无关，因为野生型和糖基磷脂酰肌醇（GPI）锚定的MT1-MMP都会脱落。这些研究为MT1-MMP胞外结构域脱落过程提供了新的见解，该过程可能调节细胞周围的蛋白水解。