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Txk中自磷酸化的证据:Y91是一个自磷酸化位点。

Evidence of autophosphorylation in Txk: Y91 is an autophosphorylation site.

作者信息

Kashiwakura Jun-Ichi, Suzuki Noboru, Takeno Mitsuhiro, Itoh Saotomo, Oku Teruaki, Sakane Tsuyoshi, Nakajin Shizuo, Toyoshima Satoshi

机构信息

Department of Biochemistry, Hoshi University, Tokyo, Japan.

出版信息

Biol Pharm Bull. 2002 Jun;25(6):718-21. doi: 10.1248/bpb.25.718.

Abstract

We have previously shown that Txk, a member of Tec family tyrosine kinase, is expressed in Th1 and ThO cells and directly contributes to gene transcription of Th1-related proteins, including interferon (IFN)-gamma, 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-gamma secretion by Jurkat T cells expressing mutant Txk proteins. While transfection with the wild-type Txk resulted in increased IFN-gamma 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-gamma 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-gamma 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.

摘要

我们之前已经表明,Tec家族酪氨酸激酶成员Txk在Th1和Th0细胞中表达,并通过响应促有丝分裂刺激的核转位直接促进包括干扰素(IFN)-γ在内的Th1相关蛋白的基因转录。Tec家族酪氨酸激酶的另一个成员Btk已被证明具有Src家族酪氨酸激酶依赖性转磷酸化位点和自磷酸化位点。然而,除了420位酪氨酸残基被确定为转磷酸化位点外,关于Txk的磷酸化机制知之甚少。在本研究中,我们通过体外激酶分析发现Txk可自身磷酸化。为了阐明磷酸化在Txk功能中的作用,我们研究了表达突变型Txk蛋白的Jurkat T细胞分泌IFN-γ的情况。虽然转染野生型Txk会导致IFN-γ产生增加,但ATP结合位点的破坏会消除该功能,而ATP结合位点可能参与自磷酸化机制。结果表明,磷酸化的Txk是促进IFN-γ合成的活性形式。通过将Txk的结构与Btk进行比较,推测Txk的91位酪氨酸残基是一个自磷酸化位点。在转染Txk Y91A的Jurkat细胞中,与转染野生型Txk的Jurkat细胞相比,IFN-γ的产生减少。这些数据表明,Txk中91位酪氨酸残基的磷酸化在Txk功能中起正调控作用。

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