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The Journal of Immunology, 2002, 168: 2365-2370.
Copyright © 2002 by The American Association of Immunologists

Txk, a Member of Nonreceptor Tyrosine Kinase of Tec Family, Acts as a Th1 Cell-Specific Transcription Factor and Regulates IFN-{gamma} Gene Transcription1

Yuko Takeba2,*, Hiroko Nagafuchi2,{dagger}, Mitsuhiro Takeno*, Jun-ichi Kashiwakura* and Noboru Suzuki3,*

* Departments of Immunology and Medicine, and {dagger} Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan

Precise mechanisms responsible for Th1 cell activation and differentiation are not fully elucidated. We have recently reported that Txk, a member of Tec family nonreceptor tyrosine kinase, is expressed on Th1/Th0 cells, and Txk regulates specifically IFN-{gamma} gene expression. In this study, we found that Txk bound to IFN-{gamma} promoter region. Txk transfection increased transcriptional activity of IFN-{gamma} promoter plus luciferase constructs severalfold, including IFN-{gamma} promoter -538, -208, and -53. IFN-{gamma} promoter -39 was refractory to the Txk transfection. The actual site to which Txk bound was the element consisting of -53 and -39 bp from the transcription start site of human IFN-{gamma} gene, a site distinct from several previously characterized binding sites. We found that the entire -53/-39 region was necessary for the binding to and function of Txk, because mutant promoter oligoDNA that contained contiguous five base substitutions dispersed throughout the -53/-39 inhibited the binding, and the mutant promoters did not respond to the Txk transfection. Similar sequences of this element are found within the 5' flanking regions of several Th1 cell-associated protein genes. Thus, Txk is expressed on Th1/Th0 cells with the IFN-{gamma} production and acts as a Th1 cell-specific transcription factor.




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