文章基本信息

标题：Evidence of Autophosphorylation in Txk: Y91 Is an Autophosphorylation Site
本地全文：下载
作者：Jun-ichi Kashiwakura ; Noboru Suzuki ; Mitsuhiro Takeno 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2002
卷号：25
期号：6
页码：718-721
DOI：10.1248/bpb.25.718
出版社：The Pharmaceutical Society of Japan
摘要：We have previously shown that Txk, a member of Tec family tyrosine kinase, is expressed in Th1 and Th0 cells and directly contributes to gene transcription of Th1-related proteins, including interferon (IFN)-γ, through nuclear translocation in response to mitogenic stimuli. Btk, another member of Tec family tyrosine kinase, has been shown to have a Src family tyrosine kinase-dependent transphosphorylation site and an autophosphorylation site. However, little is known about the phosphorylation mechanism of Txk, except that 420 tyrosine residue was identified as the transphosphorylation site. In this study, we found that Txk autophosphorylated itself by using an in vitro kinase assay. To elucidate the role of phosphorylation in Txk function, we studied IFN-γ secretion by Jurkat T cells expressing mutant Txk proteins. While transfection with the wild-type Txk resulted in increased IFN-γ production, the function was abrogated by disruption of the ATP biding site, which is presumably involved in the autophosphorylation mechanism. The results suggest that phosphorylated Txk is an active form to promote IFN-γ synthesis. The 91 tyrosine residue of Txk is deduced to be an autophosphorylation site by comparing its structure with Btk. In Jurkat cells transfected with Txk Y91A, IFN-γ production was decreased in comparison with the wild-type Txk transfected Jurkat cells. These data suggest that phosphorylation of the 91 tyrosine residue in Txk plays a positive regulatory role in Txk function.
关键词：Txk;interferon-γ;autophosphorylation;ATP binding site