Function of novel molecule Gasp exclusively expressed in the thymus

胸腺中专门表达的新分子Gasp的功能

• 批准号: 22390098
• 负责人: SUZUKI Harumi
• 金额: $ 11.65万
• 依托单位: Research Institute, International Medical Center of Japan
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390098/
• 关键词: リンパ球; 胸腺; T細胞; 分化; シグナル伝達; 正の選択; 自己免疫

We identified a novel gene Gasp (Themis), which is exclusively expressed in the thymus and reported that Themis is critical in positive selection of thymocytes. Themis is a unique molecule that is absolutely required for positive selection, but is not required for negative selection and homeostatic expansion. Themis constitutively associates with Grb2 and tyrosine phosphorylated upon TCR-stimulation, therefore likely to be involved in TCR-dependent signal transduction. It is also involved in TCR-dependent IL-2 production, however, we could not observe any sign of modulating signaling strength. From domains deletion analysis of Themis, two of CABIT domains, a proline rich sequence (PRS), and a nuclear localization signal (NLS) are all shown to be required for its function. Collectively, Themis is not simply modulating strength of signal, but may be important for sustaining weak signal required for positive selection in the thymus. Molecular mechanism of Themis is still not well known, however, the current study unveiled its importance for IL-2 production, and differential function of the two CABIT domains. Themis may not simply modulate signaling strength like other signal transducers, but it may involved in spatiotemporal regulation of intracellular signal transduction.

我们发现了一个新的基因Themis，该基因仅在胸腺中表达，并报道了Themis在胸腺细胞的正向选择中起关键作用。Themis是一种独特的分子，对于正向选择是绝对必要的，但对于负选择和体内平衡扩张则不是必需的。Themis与Grb2和TCR刺激后被磷酸化的酪氨酸结合在一起，因此可能参与TCR依赖的信号转导。它也参与TCR依赖的IL-2的产生，然而，我们没有观察到任何调节信号强度的迹象。对Themis的结构域缺失分析表明，CABIT结构域中的两个结构域、一个富含Pro的序列(Prs)和一个核定位信号(NLS)都是其功能所必需的。总的来说，Themis不是简单地调节信号的强度，而是对维持胸腺中阳性选择所需的弱信号可能是重要的。Themis的分子机制尚不清楚，但目前的研究揭示了Themis对IL-2产生的重要性，以及这两个CABIT结构域的不同功能。Themis可能不像其他信号转导分子那样简单地调节信号强度，但它可能参与细胞内信号转导的时空调节。

项目成果

Differential requirement for RhoH in development of TCRab CD8aa IELs and other types of T cells

TCRab CD8aa IEL 和其他类型 T 细胞发育过程中对 RhoH 的不同需求

• 发表时间: 2013
• 期刊: Immunol. Lett.
• 作者: Oda H;Tamehiro N;Patrich MS;Hayakawa K and Suzuki H
• 通讯作者: Hayakawa K and Suzuki H

Effect of Gasp (Themis) on T cell development and TCR signaling

Gasp (Themis) 对 T 细胞发育和 TCR 信号传导的影响

• 发表时间: 2011
• 作者: Okada;T.;Patrick M. S.;Yoshimoto;T.;Kaji;K.;Tamehiro;N.;Okamura;T.;Suzuki;H.
• 通讯作者: H.

Overexpression of Gasp (Themis) augmented positive selection of thymocytes

Gasp (Themis) 的过度表达增强了胸腺细胞的阳性选择

• 发表时间: 2011
• 作者: Okada;T.;Patrick M. S.;Yoshimoto;T.;Kaji;K.;Tamehiro;N.;Okamura;T.;Suzuki;H.
• 通讯作者: H.

Ectopic expression of a T-box transcription factor, eomesodermin, renders CD4+ Th cells cytotoxic by activating both perforin- and FasL-pathways

• DOI: 10.1016/j.imlet.2012.02.013
• 发表时间: 2012-05-30
• 期刊: IMMUNOLOGY LETTERS
• 影响因子: 4.4
• 作者: Eshima, Koji;Chiba, Sayuri;Shinohara, Nobukata
• 通讯作者: Shinohara, Nobukata

Gasp(Themis)トランスジェニックマウスの解析

Gasp(Themis)转基因小鼠分析

• 发表时间: 2011
• 作者: 岡田季之;バトリックマイケル;加地健太郎;吉本拓矢;岡村匡史;鈴木春巳
• 通讯作者: 鈴木春巳