Document Detail


Importance of serine727 phosphorylated STAT1 in IFNγ-induced signaling and apoptosis of human salivary gland cells.
MedLine Citation:
PMID:  21303487     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Aim:  It is reported that in salivary glands of Sjögren's syndrome (SS), interferon gamma (IFNγ) and IFNγ-inducible genes containing signal transducers and activators of transcription 1 (STAT1) are upregulated and play a crucial role in the pathogenesis of SS. The aim of this study is to clarify which phosphorylation of STAT1, serine727 (Ser(727) ) or tyrosine701 (Tyr(701) ) of STAT1, is important for IFNγ signaling and IFNγ-induced apoptosis in salivary gland cells. Methods:  We established STAT1 Tyr(701) variant (tyrosine to phenylalanine; Y701F) and STAT1 Ser(727) variant (serine to alanine; S727A), which were transfected into human salivary gland (HSG) cells. HSG cells transfected with these mutant-STAT1 were analyzed on the expression of IFNγ-inducible genes and apoptosis after stimulation with IFNγ. Results:  In Y701F mutant-STAT1 transfected HSG cells (Ser(727) -dominant HSG cells), IFNγ-inducible genes such as IP10, IRF1, and Fas expression were increased after stimulation with IFNγ. In Ser(727) -dominant HSG cells, the induction of apoptosis after stimulation with IFNγ was also increased compared with S727A mutant-STAT1 transfected HSG cells (Tyr(701) -dominant HSG cells). Conclusion:  Phosphorylation of Ser(727) in STAT1 might be more important in IFNγ signaling and the induction of apoptosis in HSG cells than phosphorylation of Tyr(701) . Accordingly, we propose that phosphorylation of Ser(727) in STAT1 could be a potentially suitable new therapeutic target for SS patients to prevent the destruction of salivary glands.
Authors:
Hiroto Tsuboi; Ei Wakamatsu; Mana Iizuka; Yumi Nakamura; Makoto Sugihara; Takeshi Suzuki; Hiroshi Ogishima; Taichi Hayashi; Daisuke Goto; Satoshi Ito; Isao Matsumoto; Takayuki Sumida
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Publication Detail:
Type:  Journal Article     Date:  2010-11-09
Journal Detail:
Title:  International journal of rheumatic diseases     Volume:  14     ISSN:  1756-185X     ISO Abbreviation:  Int J Rheum Dis     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-09     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101474930     Medline TA:  Int J Rheum Dis     Country:  England    
Other Details:
Languages:  eng     Pagination:  86-91     Citation Subset:  IM    
Copyright Information:
© 2010 The Authors. International Journal of Rheumatic Diseases © 2010 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.
Affiliation:
Division of Clinical Immunology, Doctoral Programs in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA Japan Society for the Promotion of Science, Tokyo, Japan.
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