Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombospondin motifs as an inflammation associated gene
Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombospondin motifs as an inflammation associated gene
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DOI：
10.1074/jbc.272.1.556
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发表时间：
1997-01-03
影响因子：
4.8
通讯作者：
Matsushima, K
中科院分区：
文献类型：
--
作者：
Kuno, K;Kanada, N;Matsushima, K
细胞崩解素和金属蛋白酶（ADAM）是一个与蛇毒金属蛋白酶和崩解素具有结构同源性的新基因家族。我们在体内筛选了在恶病质性结肠腺癌亚群中选择性表达的基因。发现一个新的cDNA克隆，被鉴定为恶病质肿瘤选择基因，编码一个富含半胱氨酸的蛋白，其序列与蛇毒金属蛋白酶和血栓反应蛋白相似。我们将该cDNA克隆命名为带血栓反应蛋白基序的A崩解素和金属蛋白酶（ADAMTS-1）。ADAMTS1由6个结构域组成，1)一个金属蛋白酶前体和2)一个金属蛋白酶，3)一个崩解素样结构域，4)一个包含TSP I型基序的血栓反应蛋白（TSP）同源结构域，5)一个间隔区，6)cooh末端TSP亚基。与其他ADAMs不同，ADAMTS-1不具有跨膜结构域，是一种推定的分泌蛋白。因此，ADAMTS-1是一种具有TSP I型基序的新型ADAM家族蛋白。我们证明了包含ADAMTS-1的TSP型I基序的TSP同源结构域具有与肝素结合的功能。体外用炎性细胞因子白细胞介素-1刺激结肠26细胞可诱导ADAMTS-1 mRNA表达。此外，小鼠静脉注射脂多糖选择性诱导肾脏和心脏ADAMTS-1 mRNA表达。这些数据表明，ADAM-TS-1可能是一个基因，其表达与各种炎症过程以及癌症恶病质的发展有关。
A cellular disintegrin and metalloproteinase (ADAM) is a new family of genes with structural homology to the snake venom metalloproteinases and disintegrins. We screened genes which were selectively expressed in the cachexigenic colon 26 adenocarcinoma subline in vivo. It was found that one novel cDNA clone, identified as a cachexigenic tumor selective gene, encodes a cysteine-rich protein which shows a sequence similarity to that of both the snake venom metalloproteinases and thrombospondins. We named this cDNA clone A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-1). ADAMTS1 consists of six domains, 1) a pro- and 2) a metalloproteinase, 3) a disintegrin-like, 4) a thrombospondin (TSP) homologous domain containing TSP type I motif, 5) a spacer region, and 6) COOH-terminal TSP submotifs. Unlike other ADAMs, ADAMTS-1 does not possess a transmembrane domain and is a putative secretory protein. Therefore, ADAMTS-1 is a new type of ADAM family protein with TSP type I motifs. We demonstrated that the TSP homologous domain containing the TSP type I motif of ADAMTS-1 is functional for binding to heparin. ADAMTS-1 mRNA could be induced by stimulating colon 26 cells with an inflammatory cytokine, interleukin-1, in vitro. Moreover, intravenous administration of lipopolysaccharide in mice selectively induced ADAMTS-1 mRNA in kidney and heart. These data suggest that ADAM-TS-1 may be a gene whose expression is associated with various inflammatory processes as well as development of cancer cachexia.