Stat6-protease but not Stat5-protease is inhibited by an elastase inhibitor ONO-5046.
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.
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008894:Milk Proteins; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor; D050800:STAT6 Transcription Factor; D013449:Sulfonamides / Q000494:pharmacology*; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D013449:Sulfonamides; D015534:Trans-Activators; C069195:sivelestat; D010196:Pancreatic Elastase; D005998:Glycine