THE GENE STRUCTURE OF TISSUE INHIBITOR OF METALLOPROTEINASES (TIMP)-3 AND ITS INHIBITORY ACTIVITIES DEFINE THE DISTINCT TIMP GENE FAMILY
THE GENE STRUCTURE OF TISSUE INHIBITOR OF METALLOPROTEINASES (TIMP)-3 AND ITS INHIBITORY ACTIVITIES DEFINE THE DISTINCT TIMP GENE FAMILY
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DOI：
10.1074/jbc.270.24.14313
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发表时间：
1995-06-16
影响因子：
4.8
通讯作者：
MURPHY, G
中科院分区：
文献类型：
--
作者：
APTE, SS;OLSEN, BR;MURPHY, G
基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）在细胞外基质的稳态中起着关键作用。我们以前克隆了人和小鼠TIMP-3 cDNA并绘制了它们的染色体基因座（Apte，S.美国，Mattei，M-G.，和Olsen，B. R.等人（1994）Genomics 19，86-90; Apte，S.美国，Hayashi，K.，Seldin，M. F.、Mattei，M-G;.，林，M.，和Olsen，B. R.（1994）Dev.戴纳姆200，177-197）; Sorsby眼底营养不良中TIMP 3突变的鉴定已经强调了功能的重要性！TIMP-3我们现在报告，TIMP-3编码的5个外显子跨越30个双链酶对小鼠基因组DNA。在将蛋白质结构域归因于特定外显子以及外显子结构方面，Timp-3和Timp-1基因是相似的，这证实了TIMP的共同进化起源并定义了不同的基因家族。我们已经在小鼠NSO骨髓瘤细胞中表达了人和小鼠TIMP-3。在每种情况下，N-糖基化。27-产生kDa蛋白，其与TIMP-1和TIMP-2一样，抑制胶原酶-1、基质溶解素-1和明胶酶A和B。TIMP-3和TIMP-1的抑制作用在数量上相似，这意味着所有TIMP在MMP抑制中同样有效。相反，TIMP基因或不同的C-末端蛋白质序列的差异调节可能是每种TIMP不同生物学功能的基础。
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play a critical role in extracellular matrix homeostasis. We have previously cloned human and mouse TIMP-3 cDNAs and mapped their chromosomal loci (Apte, S. S., Mattei, M-G., and Olsen, B. R. (1994) Genomics 19, 86-90; Apte, S. S., Hayashi, K., Seldin, M. F., Mattei, M-G;., Hayashi, M., and Olsen, B. R. (1994) Dev. Dynam. 200, 177-197); the identification of TIMP3 mutations in Sorsby's fundus dystrophy has underscored the functional importance! of TIMP-3. We now report that TIMP-3 is encoded by five exons spanning over 30 kilobase pairs of mouse genomic DNA. In the attribution of protein domains to specific exons, as well as exon structures, the Timp-3 and Timp-1 genes are similar, confirming the common evolutionary origin of the TIMPs and defining a distinct gene family. We have expressed human and mouse TIMP-3 in mouse NSO myeloma cells. In each case, an N-glycosylated. 27-kDa protein was generated, that, like TIMP-1 and TIMP-2, inhibited collagenase-1, stromelysin-1, and gelatinases A and B. TIMP-3 and TIMP-1 inhibition were quantitatively similar, implying that all TIMPs are equally efficient in MMP inhibition. Instead, differential regulation of the TIMP genes or divergent C-terminal protein sequences may underlie distinct biological functions for each TIMP.