MATRIX METALLOPROTEINASE-7 (MATRILYSIN) FROM HUMAN RECTAL-CARCINOMA CELLS - ACTIVATION OF THE PRECURSOR, INTERACTION WITH OTHER MATRIX METALLOPROTEINASES AND ENZYMATIC-PROPERTIES
MATRIX METALLOPROTEINASE-7 (MATRILYSIN) FROM HUMAN RECTAL-CARCINOMA CELLS - ACTIVATION OF THE PRECURSOR, INTERACTION WITH OTHER MATRIX METALLOPROTEINASES AND ENZYMATIC-PROPERTIES
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DOI：
10.1074/jbc.270.12.6691
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发表时间：
1995-03-24
影响因子：
4.8
通讯作者：
OKADA, Y
中科院分区：
文献类型：
--
作者：
IMAI, K;YOKOHAMA, Y;OKADA, Y
基质金属蛋白酶7（MMP-7）是从CaR-1人直肠癌细胞的培养基中纯化的M（r）28，000（proMMP-7）的无活性酶原。proMMP-7的NH 2-末端序列为Lys-Pro-Lys-Pro-Gln-Glu，其与matrilysin的相同。酶原被4-氨基苯汞乙酸（APMA）激活，产生M（r）21，000的中间形式和M（r）19，000的活性物质，其显示新的N端序列Tyr（78）-Ser-Leu-Phe-Pro-Asn-Ser。MMP-3可激活ProMMP-7 MMP-1和MMP-2（基质溶解素1）在一步机制中被激活至其全部活性，并产生与通过APMA活化获得的相同的NH 2末端，而MMP-1和MMP-2在一步机制中被激活至其全部活性，并产生与通过APMA活化获得的相同的NH 2末端。（组织胶原酶），MMP-2（明胶酶A）和MMP-9（明胶酶B）不具有这样的作用，另一方面，proMMP-1被MMP-7激活至与APMA获得的活性相似的活性，并且在APMA存在下，MMP-7的激活增强至相似的6.5倍，这种增强的活性是由proMMP-1的Gln（80）-Phe（81）键处的特异性裂解提供的。MMP-7也可以激活proMMP-9高达接近50%的全活性，具有Leu（16）-Arg-Thr-（Asn）-Leu的新的NH 2末端。proMMP-2或proMMP-3与MMP-7的孵育不导致这些proMMP的活化。MMP-7降解IV型胶原、层粘连蛋白-1、纤连蛋白、蛋白聚糖、I型明胶和不溶性弹性蛋白。这些结果表明，在体内MMP-7可能在病理条件下与MMP-1、-3和-9一起降解细胞外基质大分子中发挥作用。
Matrix metalloproteinase 7 (MMP-7) has been purified as an inactive zymogen of M(r), 28,000 (proMMP-7) from the culture medium of CaR-1 human rectal carcinoma cells. The NH2-terminal sequence of proMMP-7 is Lys-Pro-Lys-Pro-Gln-Glu, which is identical to that of matrilysin. The zymogen is activated by 4-aminophenylmercuric acetate (APMA), yielding an intermediate form of M(r) 21,000 and an active species of M(r) 19,000 which shows the new NH2-terminal sequence of Tyr(78)-Ser-Leu-Phe-Pro-Asn-Ser. Although trypsin fully activates the zymogen, the activation rate by plasmin or leukocyte elastase is confined to similar to 50%. ProMMP-7 can be activated by MMP-3 (stromelysin 1) to its full activity in a single-step mechanism and generates the same NH2 terminus obtained by APMA activation, whereas MMP-1 (tissue collagenase), MMP-2 (gelatinase A), and MMP-9 (gelatinase B) do not have such an effect, On the other hand, proMMP-1 is activated by MMP-7 to an activity similar to that obtained by APMA and the activation by MMP-7 is enhanced up to similar to 6.5 fold in the presence of APMA, This enhanced activity is donated by specific cleavage at the Gln(80)-Phe(81) bond of proMMP-1. MMP-7 can also activate proMMP-9 up to similar to 50% of the full activity with a new NH2 terminus of Leu(16)-Arg-Thr-(Asn)-Leu. Incubation of proMMP-2 or proMMP-3 with MMP-7 results in no activation of these proMMPs. MMP-7 degrades type IV collagen, laminin-1, fibronectin, proteoglycan, type I gelatin, and insoluble elastin, These results suggest that in vivo MMP-7 may play a role in degradation of extracellular matrix macromolecules in concert with MMP-1, -3, and -9 under pathological conditions.