Stat6-protease but not Stat5-protease is inhibited by an elastase inhibitor ONO-5046 |
| |
Authors: | Suzuki Kotaro Nakajima Hiroshi Ikeda Kei Tamachi Tomohiro Hiwasa Takaki Saito Yasushi Iwamoto Itsuo |
| |
Institution: | Department of Internal Medicine II, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan. |
| |
Abstract: | 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. |
| |
Keywords: | STAT protease Proteolysis Elastase family |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|