Isolation and analysis of new memnrane-type matrix metalloproteinases

新型膜型基质金属蛋白酶的分离与分析

• 批准号: 10470028
• 负责人: SEIKI Motoharu
• 金额: $ 8.26万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470028/
• 关键词: MMP; MT-MMP; GPI; マトリックスメタロプロテアーゼ; 膜型酵素; がんの浸潤・転移; MT4-MMP; 細胞外基質分解酵素

1. At the beginning of this study, four distinct membrane-type matrix metalloproteinases (MT-MMPs) has been identified. Since the fourth member, MT4-MMP, lacks signal peptide sequence in the reported DNA, we re-analyzed transcripts for MT4-MMP in human and mouse cells. In human, two types of the transcripts were identified and one corresponded to the previously reported one. The other transcript was found to encode signal peptide a part of propeptide sequence that was missing in the previously reported one. Thus, functional gene was firstly identfied. Similarly, mouse cDNA was also identified.2. The carboxy terminal region of MT4-MMP is distantly related to other MT-MMP membaers that have a hydrophobic amino acid streatch acting transmembrane domain. Although the C-terminal amino acids of MT4-MMP is also hydrophobic, it was demonstarted that the sequence was a signal for processing and for glycosyal phosphatidial inositol anchoring.3. Fifth member of MT-MMP group was identified by cDNA cloning. It was found to be expressed selectively in cereberum and thoght to be important for the development and maintenance of central nervous system.

1. 在这项研究的开始，已经确定了四种不同的膜型基质金属蛋白酶（MT-MMPs）。由于第四个成员MT4-MMP在报道的DNA中缺乏信号肽序列，我们重新分析了人和小鼠细胞中MT4-MMP的转录本。在人类中，鉴定出两种类型的转录本，其中一种与先前报道的转录本相对应。另一个转录本编码信号肽，这是先前报道的一个缺失的前肽序列的一部分。从而首次鉴定出功能基因。同样，小鼠cDNA也得到了鉴定。MT4-MMP的羧基末端区域与其他具有疏水氨基酸拉伸作用跨膜结构域的MT-MMP成员有远亲关系。虽然MT4-MMP的c端氨基酸也是疏水的，但已经证明该序列是加工和糖基磷脂肌醇锚定的信号。通过cDNA克隆鉴定MT-MMP组的第5个成员。它在小脑中选择性表达，对中枢神经系统的发育和维持起重要作用。

项目成果

清木 元治: "MT1-MMP and MMP-2 mRNA expression in human ovarian tumors: possible implications for the role of desmoplastic fibroblasts." Human Pathology. 29. 155-165 (1998)

Motoharu Kiyoki：“人类卵巢肿瘤中的 MT1-MMP 和 MMP-2 mRNA 表达：对促纤维增生性成纤维细胞的作用的可能影响。”29. 155-165 (1998)

Itoh, Y. et al.: "Membrane-type 4 matrix metalloproteinase (MT4-MMP, MMP-17) is a glycosylphosphatidyl inositol (GPI)-anchored proteinase"J. Biol. Chem.. 274. 34260-34266 (1999)

Itoh, Y. 等人：“膜型 4 基质金属蛋白酶（MT4-MMP、MMP-17）是一种糖基磷脂酰肌醇 (GPI) 锚定的蛋白酶”J.

Kinoh, H. et al.: "Assignment(1) of the genes for membrane-type-4 matrix metalloproteinase (Mmp17, MMP17) to mouse chromosome 5, human chromosome band 12q24.3 and membrane-type-5 matrix metalloproteinase (Mmp24, MMP24) to mouse chromosome 2 and human chro

Kinoh, H. 等人：“将 4 型膜基质金属蛋白酶 (Mmp17、MMP17) 基因分配 (1) 至小鼠 5 号染色体、人类染色体带 12q24.3 和 5 型膜基质金属蛋白酶 (Mmp24)

Itoh,Y et al.: "Membrance-type 4 matrix metalloproteinase(MT4-MMP,MMP-17) is a gycosylphosphatidyl inositol (GPI)-anchored proteinase"J.Biol.Chem.. 274. 34260-34266 (1999)

Itoh,Y 等人：“膜型 4 基质金属蛋白酶（MT4-MMP、MMP-17）是一种糖基磷脂酰肌醇 (GPI) 锚定的蛋白酶”J.Biol.Chem.. 274. 34260-34266 (1999)

Kajita, M. et al.: "Human Membrane Type-4 Matrix Metalloproteinase (MT4-MMP) is encoded by a novel major transcript"FEBS Letter. 457. 353-356 (1999)

Kajita, M. 等人：“人膜 4 型基质金属蛋白酶 (MT4-MMP) 由新的主要转录本编码”FEBS Letter。