Membrane type 4 matrix metalloproteinase (MT4-MMP, MMP-17) is a glycosylphosphatidylinositol-anchored proteinase
Membrane type 4 matrix metalloproteinase (MT4-MMP, MMP-17) is a glycosylphosphatidylinositol-anchored proteinase
复制标题
DOI：
10.1074/jbc.274.48.34260
复制
发表时间：
1999-11-26
影响因子：
4.8
通讯作者：
Seiki, M
中科院分区：
文献类型：
--
作者：
Itoh, Y;Kajita, M;Seiki, M
在五种膜型基质金属蛋白酶（MT-MMPs）中，MT 1-、MT 2-、MT3-和MT5-MMPs在跨膜结构域之后具有约20个氨基酸的胞质尾。与此相反，MT4-MMP的跨膜结构域位于C-末端，预期的胞质尾很短或不存在，这样的序列通常作为糖基磷脂酰肌醇（GPI）锚定信号而不是作为跨膜结构域，因此我们研究了MT4-MMP是GPI锚定蛋白酶的可能性。其可以被掺入GPI单元中，以序列依赖性方式特异性标记MT4-MMP C-末端。此外，磷脂酰肌醇特异性磷脂酶C处理从转染细胞表面释放MT4-MMP。这些结果表明，MT4-MMP是MMP家族中第一个GPI锚定的蛋白酶。在转染细胞的培养过程中，MT4-MMP似乎是通过内源性金属蛋白酶的作用从细胞表面脱落的。MT4-MMP在细胞表面的GPI锚定表明该蛋白酶具有独特的生物学功能和特征。
Among the five membrane-type matrix metalloproteinases (MT-MMPs), MT1-, MT2-, MT3-, and MT5-MMPs have about a 20-amino acid cytoplasmic tail following the transmembrane domain. In contrast, a putative transmembrane domain of MT4-MMP locates at the very C-terminal end, and the expected cytoplasmic tail is very short or nonexistent, Such sequences often act as a glycosylphosphatidylinositol (GPI) anchoring signal rather than as a transmembrane domain, We thus examined the possibility that MT4-MMP is a GPI-anchored proteinase, Our results showed that [H-3]ethanolamine, which can be incorporated into the GPI unit, specifically labeled the MT4-MMP C-terminal end in a sequence-dependent manner. In addition, phosphatidylinositol-specific phospholipase C treatment released the MT4-MMP from the surface of transfected calls. These results indicate that MT4-MMP is the first GPI-anchored proteinase in the MMP family, During cultivation of the transfected cells, MT4-MMP appeared to be shed from the cell surface by the action of an endogenous metalloproteinase. GPI anchoring of MT4-MMP on the cell surface indicates a unique biological function and character for this proteinase.