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Publication : Proteolytic processing of Stat6 signaling in mast cells as a negative regulatory mechanism.

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.
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