Tissue inhibitor of metalloproteinase (TIMP-2). A new member of the metalloproteinase inhibitor family.
Tissue inhibitor of metalloproteinase (TIMP-2). A new member of the metalloproteinase inhibitor family.
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DOI：
10.1016/s0021-9258(18)71503-2
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发表时间：
1989-10
期刊：
影响因子：
--
通讯作者：
W. Stetler-Stevenson;H. Krutzsch;L. Liotta
中科院分区：
文献类型：
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作者：
W. Stetler-Stevenson;H. Krutzsch;L. Liotta
人类黑色素瘤细胞分泌一种名为CSC-21 K的21 kDa蛋白质，该蛋白质以1：1摩尔化学计量比与相同细胞分泌的基质金属蛋白酶IV型胶原酶酶原（70 kDa明胶酶）结合。该结合蛋白已被纯化，其完整的一级结构通过对跨越整个蛋白的重叠肽进行测序来确定。氨基酸序列表明该蛋白与人TIMP（金属蛋白酶组织抑制剂）具有显著的同源性，包括12个半胱氨酸残基和4个色氨酸残基中的3个的位置的保守性。CSC-21 K的鉴定表明存在TIMP相关蛋白家族。该家族的个体成员可能对基质金属蛋白酶家族的不同成员具有选择性亲和力。由肿瘤细胞产生的CSC-21 K被分离为与IV型前胶原酶的1：1摩尔复合物，如通过氨基酸组成分析所证明的。向活化的金属蛋白酶中加入纯化的CSC-21 K导致以化学计量方式抑制胶原溶解活性。基于其与TIMP的序列同源性和抑制IV型胶原溶解的能力，我们建议将该抑制剂命名为TIMP-2。
Human melanoma cells secret a 21-kDa protein, termed CSC-21K, which binds with 1:1 molar stoichiometry to the matrix metalloproteinase type IV collagenase proenzyme (70-kDa gelatinase) secreted by the same cells. This binding protein has been purified and its complete primary structure determined by sequencing overlapping peptides which span the entire protein. The amino acid sequence demonstrates that this protein shares significant homology with human TIMP (tissue inhibitor of metalloproteinase), including conservation of the positions of the 12 cysteine residues and 3 of 4 tryptophan residues. The identification of CSC-21K now indicates that a family of TIMP-related proteins exists. Individual members of this family may possess selective affinities for different members of the matrix metalloproteinase family. CSC-21K produced by tumor cells is isolated as a 1:1 molar complex with type IV procollagenase, as demonstrated by amino acid composition analysis. Addition of purified CSC-21K to the activated metalloproteinase results in inhibition of the collagenolytic activity in a stoichiometric fashion. Based on its sequence homology to TIMP and ability to inhibit type IV collagenolysis we propose the name TIMP-2 for this inhibitor.