Miyamori H, Takino T, Seiki M, Sato H
Department of Molecular Virology, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-0934, Japan.
Biochem Biophys Res Commun. 2000 Jan 27;267(3):796-800. doi: 10.1006/bbrc.1999.2050.
Transfection of the mouse membrane type-2 matrix metalloproteinase (MT2-MMP) gene into COS-1 cells resulted in activation of progelatinase A; however, that of the human gene had no effect. Expression of human and mouse MT2-MMP chimeric proteins revealed the defect of human MT2-MMP which resides in the region between amino acid (aa) residues 155 and 271. Seven aa residues in this region were not conserved between human and mouse MT2-MMP. Substitution with the corresponding mouse residue, proline-183 to serine and glutamine-185 to aspartic acid, recovered cell-associated progelatinase A activation function. These residues are located in the insertion sequence-2 (IS-2), which was conserved in six clones of the human MT2-MMP gene from different sources, except that of proline-183 which was substituted with serine from HT1080 cells. These results indicate that human MT2-MMP is defective in cell-associated activation of progelatinase A, and this is attributed to IS-2. These findings emphasize the importance of IS-2 in MT2-MMP functionality.
将小鼠膜型2基质金属蛋白酶（MT2 - MMP）基因转染到COS - 1细胞中可导致前明胶酶A的激活；然而，转染人MT2 - MMP基因则没有效果。人和小鼠MT2 - MMP嵌合蛋白的表达揭示了人MT2 - MMP在氨基酸（aa）残基155和271之间区域存在缺陷。该区域的七个氨基酸残基在人和小鼠MT2 - MMP之间不保守。用相应的小鼠残基进行替换，即将脯氨酸 - 183替换为丝氨酸以及将谷氨酰胺 - 185替换为天冬氨酸，可恢复细胞相关的前明胶酶A激活功能。这些残基位于插入序列 - 2（IS - 2）中，该序列在来自不同来源的人MT2 - MMP基因的六个克隆中是保守的，但来自HT1080细胞的克隆中脯氨酸 - 183被丝氨酸替换除外。这些结果表明，人MT2 - MMP在前明胶酶A的细胞相关激活方面存在缺陷，这归因于IS - 2。这些发现强调了IS - 2在MT2 - MMP功能中的重要性。
