Activation of precursors for matrix metalloproteinases 1 (interstitial collagenase) and 3 (stromelysin) by rat mast-cell proteinases I and II.
Activation of precursors for matrix metalloproteinases 1 (interstitial collagenase) and 3 (stromelysin) by rat mast-cell proteinases I and II.
复制标题
大鼠肥大细胞蛋白酶 I 和 II 激活基质金属蛋白酶 1（间质胶原酶）和 3（基质溶解素）的前体。
DOI：
10.1042/bj3050301
复制
发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Woolley,DE
中科院分区：
文献类型：
--
作者：
Suzuki,K;Lees,M;Newlands,GF;Nagase,H;Woolley,DE
组织学研究先前已证明肥大细胞活化/脱颗粒与体内结缔组织溶解区域之间存在关联。此外，肥大细胞提取物已被证明可以激活潜在形式的胶原酶和溶基质素。在本研究中，我们研究了大鼠肥大细胞蛋白酶 (RMCP) I 和 RMCP II 作为基质金属蛋白酶 (MMP)-1（间质胶原酶）、MMP-2（明胶酶 A）和 MMP-3（溶基质素 1）前体激活剂的潜在作用。 RMCP I 和 II 均通过将 57 kDa 前体转化为 45 kDa 多肽来激活 proMMP-3。 RMCP II 激活的 45 kDa MMP-3 的 N 端氨基酸被鉴定为 Phe83。相比之下，只有 RMCP II 通过将 52 kDa proMMP-1 转化为 41 kDa 蛋白质并生成新的 N 末端（即 Gln80 和 Val82）来激活它。这种裂解产生的胶原蛋白溶解活性仅为全部活性的 35%，但这不能通过随后用 MMP-3 处理来增强，后者是与其他丝氨酸蛋白酶结合产生 N 末端带有 Phe81 的完全活性 MMP-1 的关键酶。因此，RMCP II 通过与其他胰蛋白酶样酶和 MMP-3 组合逐步加工所报道的机制不同的机制激活 proMMP-1。尽管加工成较小的产品，ProMMP-2（明胶酶原 A）不会被 RMCP I 或 RMCP II 激活。
Histological studies have previously demonstrated an association between mast-cell activation/degranulation and areas of connective-tissue lysisin vivo; in addition, mast-cell extracts have been shown to activate latent forms of collagenase and stromelysin. In the present study we have examined the potential roles of rat mast-cell proteinase (RMCP) I and RMCP II as activators of the precursors of matrix metalloproteinase (MMP)-1 (interstitial collagenase), MMP-2 (gelatinase A) and MMP-3 (stromelysin 1). Both RMCPs I and II activated proMMP-3 by converting the 57 kDa precursor into a 45 kDa polypeptide. The N-terminal amino acid of 45 kDa MMP-3 activated by RMCP II was identified as Phe83. By contrast, only RMCP II activated the 52 kDa proMMP-1 by converting it into a 41 kDa protein and generating the new N-termini, namely Gln80 and Val82. The collagenolytic activity which resulted from this cleavage was only 35% of the full activity, but this could not be augmented by subsequent treatment with MMP-3, the latter being a crucial enzyme for the generation of the fully active MMP-1 with Phe81 at the N-terminus, in conjunction with other serine proteinases. Thus RMCP II activates proMMP-1 via a mechanism different from that reported for the stepwise processing by combinations of other trypsin-like enzymes and MMP-3. ProMMP-2 (pro-gelatinase A) was not activated by either RMCP I or RMCP II, despite processing to smaller products.