First Author | Suzuki K | Year | 2002 |
Journal | J Exp Med | Volume | 196 |
Issue | 1 | Pages | 27-38 |
PubMed ID | 12093868 | Mgi Jnum | J:77505 |
Mgi Id | MGI:2181901 | Doi | 10.1084/jem.20011682 |
Citation | Suzuki K, et al. (2002) Proteolytic processing of Stat6 signaling in mast cells as a negative regulatory mechanism. J Exp Med 196(1):27-38 |
abstractText | Accumulating evidence has shown the importance of Stat6-mediated signaling in allergic diseases. In this study, we show a novel regulatory mechanism of Stat6-mediated signaling in mast cells. When Stat6 is activated by interleukin (IL)-4 and translocated to the nucleus, Stat6 is cleaved by a nucleus-associated protease in mast cells. The cleaved 65-kD Stat6 lacks the COOH-terminal transactivation domain and functions as a dominant-negative molecule to Stat6-mediated transcription. The retrovirus-mediated expression of cleavage-resistant Stat6 mutants prolongs the nuclear accumulation of Stat6 upon IL-4 stimulation and enhances IL-4-induced gene expression and growth inhibition in mast cells. These results indicate that the proteolytic processing of Stat6 functions as a lineage-specific negative regulator of Stat6-dependent signaling in mast cells, and thus suggest that it may account for the limited role of Stat6 in IL-4 signaling in mast cells. |