Pei D
Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
J Biol Chem. 1999 Mar 26;274(13):8925-32. doi: 10.1074/jbc.274.13.8925.
A new member of the membrane-type matrix metalloproteinase (MT-MMP) subfamily tentatively named MT5-MMP was isolated from mouse brain cDNA library. It is predicted to contain (i) a candidate signal sequence, (ii) a propeptide region with the highly conserved PRCGVPD sequence, (iii) a potential furin recognition motif RRRRNKR, (iv) a zinc-binding catalytic domain, (v) a hemopexin-like domain, (vi) a 24-residue hydrophobic domain as a potential transmembrane domain, and (vii) a short cytosolic domain. Reverse transcriptase-polymerase chain reaction analysis of its transcripts indicates that MT5-MMP is expressed in a brain-specific manner consistent with the origin of its EST clone from cerebellum. It is also highly expressed during embryonic development at stages day 11 and 15. Like other MT-MMPs, MT5-MMP specifically activates progelatinase A when co-expressed in Madin-Darby canine kidney cells. Its ability to activate progelatinase A is dependent on its proteolytic activity since a mutation converting Glu to Ala in the zinc binding motif HE255LGH renders MT5-MMP inactive against progelatinase A. In contrast to other MT-MMPs, MT5-MMP tends to shed from cell surface as soluble proteinases, thus offering flexibility as both a cell bound and soluble proteinase for extracellular matrix remodeling processes. Taken together, these properties serve to distinguish MT5-MMP as a versatile MT-MMP playing an important role in extracellular matrix remodeling events in the brain and during embryonic development.
从小鼠脑cDNA文库中分离出一种膜型基质金属蛋白酶（MT-MMP）亚家族的新成员，暂命名为MT5-MMP。预计它包含：（i）一个候选信号序列；（ii）一个具有高度保守PRCGVPD序列的前肽区；（iii）一个潜在的弗林蛋白酶识别基序RRRRNKR；（iv）一个锌结合催化结构域；（v）一个血红素结合蛋白样结构域；（vi）一个由24个残基组成的疏水结构域作为潜在的跨膜结构域；以及（vii）一个短的胞质结构域。对其转录本的逆转录聚合酶链反应分析表明，MT5-MMP以脑特异性方式表达，这与其EST克隆来源于小脑一致。在胚胎发育的第11天和第15阶段也有高表达。与其他MT-MMPs一样，MT5-MMP在Madin-Darby犬肾细胞中共表达时能特异性激活前明胶酶A。其激活前明胶酶A的能力依赖于其蛋白水解活性，因为锌结合基序HE255LGH中谷氨酸突变为丙氨酸会使MT5-MMP对前明胶酶A无活性。与其他MT-MMPs不同，MT5-MMP倾向于作为可溶性蛋白酶从细胞表面脱落，因此作为细胞结合型和可溶性蛋白酶在细胞外基质重塑过程中都具有灵活性。综上所述，这些特性使MT5-MMP成为一种多功能的MT-MMP，在脑和胚胎发育过程中的细胞外基质重塑事件中发挥重要作用。
