Stat6-protease but not Stat5-protease is inhibited by an elastase inhibitor ONO-5046.
Stat6-protease but not Stat5-protease is inhibited by an elastase inhibitor ONO-5046.
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DOI：
10.1016/j.bbrc.2003.08.067
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发表时间：
2003-10
影响因子：
3.1
通讯作者：
Kotaro Suzuki;H. Nakajima;K. Ikeda;T. Tamachi;T. Hiwasa;Y. Saito;I. Iwamoto
中科院分区：
文献类型：
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作者：
Kotaro Suzuki;H. Nakajima;K. Ikeda;T. Tamachi;T. Hiwasa;Y. Saito;I. Iwamoto
Stat6的短异构体（65-kDa Stat6）是细胞核中一种未定义的蛋白酶（Stat6蛋白酶）的蛋白水解加工产物，下调肥大细胞中Stat6介导的信号传导。同样，stat5介导的信号在髓系祖细胞中被stat5蛋白酶下调。这些蛋白酶有许多共同的特征，包括它们的核定位和对蛋白酶抑制剂的易感性。在这里，我们进一步研究了这些Stat蛋白酶。有趣的是，stat6蛋白酶的活性被ONO-5046（一种抑制中性粒细胞弹性酶（NE）和NE相关蛋白酶蛋白酶3 （PR3）活性的弹性酶抑制剂）所抑制，而stat5蛋白酶的活性则未被抑制。尽管NE和PR3都能在体外切割Stat6，但NE或PR3在肥大细胞中切割Stat6的位点与Stat6蛋白酶在肥大细胞中的切割位点不同。此外，NE和PR3也可以切割Stat5，但它们与髓系祖细胞中的Stat5蛋白酶不同。这些结果表明stat6蛋白酶可能属于弹性蛋白酶家族，但与NE或PR3不同。
A short isoform of Stat6 (65-kDa Stat6), a product of proteolytic processing by an undefined protease (Stat6-protease) in the nucleus, downregulates Stat6-mediated signaling in mast cells. Similarly, Stat5-mediated signaling is downregulated by Stat5-protease in myeloid progenitors. These proteases share a number of characteristics, including their nuclear localization and susceptibility to protease inhibitors. Here, we further investigated these Stat proteases. Interestingly, the activity of Stat6-protease but not of Stat5-protease was inhibited by ONO-5046, an elastase inhibitor that inhibits the activity of neutrophil elastase (NE) and NE-related protease proteinase 3 (PR3). Although both NE and PR3 were able to cleave Stat6 in vitro, the cleavage sites of Stat6 by NE or PR3 differed from that by Stat6-protease in mast cells. In addition, both NE and PR3 could also cleave Stat5, but they differed from Stat5-protease in myeloid progenitors. These results suggest that Stat6-protease may belong to the elastase family but differs from NE or PR3.