Trapping Grb2 within immune cells: The role of transmembrane adaptor proteins

将 Grb2 捕获在免疫细胞内：跨膜接头蛋白的作用

• 批准号: 5412690
• 负责人: Professor Dr. Luca Simeoni
• 金额: --
• 依托单位: Institut für Molekulare und Klinische Immunologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2003
• 资助国家: 德国
• 起止时间: 2002-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5412690?language=en
• 关键词: Trapping; Grb2; within; immune; cells

SIT is a recently discovered transmembrane adaptor molecule that represents a regulator of signals emanating from the T cell receptor. Previous work from our laboratory has shown that, depending on its phosphorylation status, SIT can act as a positive or a negative signaling element of T-cell activation in Jurkat T cells. To further extend the studies on the function of SIT and to assess its role in vivo we have produced SIT knock-out mice. SIT deficient mice exhibit a defect in the development of ab-T cells and show a 2-3 fold higher number of gd-T-lymphocytes in the peripheral lymphoid organs. The aim of this project is to investigate the mechanisms by which SIT can affect development and homing of T lymphocytes, as well as its function in B-lymphocytes and plasma-cells, which has yet to be investigated. Mice lacking SIT will be used to dissect (i) thymic selection processes (positive and negative selection in a TCR transgenic background) and (ii) intracellular biochemical cascades after the triggering the T-cell receptor in thymocytes. In addition to the evaluation of the differentiation potential of T-cells, we will focus our investigation on the function of peripheral T-, B- and plasma cells (proliferation, immune response and homing). Finally, we will develop additional animal models (SIT transgenic mice, SIT/TRIM double knock-out mice) to further expand our study of SIT function.

SIT是最近发现的跨膜接头分子，其代表从T细胞受体发出的信号的调节剂。我们实验室以前的工作表明，根据其磷酸化状态，SIT可以作为Jurkat T细胞中T细胞活化的正或负信号元件。为了进一步扩展对SIT功能的研究并评估其在体内的作用，我们已经产生了SIT敲除小鼠。SIT缺陷小鼠在ab-T细胞发育中表现出缺陷，并且在外周淋巴器官中显示出2-3倍高的gd-T淋巴细胞数量。本项目的目的是研究SIT可以影响T淋巴细胞的发育和归巢的机制，以及其在B淋巴细胞和浆细胞中的功能，这还有待研究。缺乏SIT的小鼠将用于剖析（i）胸腺选择过程（TCR转基因背景中的阳性和阴性选择）和（ii）触发胸腺细胞中的T细胞受体后的细胞内生化级联。除了对T细胞的分化潜能进行评估外，我们还将重点研究外周T细胞、B细胞和浆细胞的功能（增殖、免疫应答和归巢）。最后，我们将开发更多的动物模型（SIT转基因小鼠，SIT/TRIM双敲除小鼠），以进一步扩大我们对SIT功能的研究。

项目成果

TCR‐mediated Erk activation does not depend on Sos and Grb2 in peripheral human T cells

• DOI: 10.1038/embor.2012.17
• 发表时间: 2012-04
• 期刊: EMBO reports
• 影响因子: 7.7
• 作者: Nicole Warnecke;M. Poltorak;B. Kowtharapu;Boerge Arndt;J. Stone;B. Schraven;L. Simeoni

Cooperative immunoregulatory function of the transmembrane adaptor proteins SIT and LAX

跨膜接头蛋白 SIT 和 LAX 的协同免疫调节功能

• DOI: 10.1189/jlb.0312152
• 发表时间: 2013
• 期刊: Journal of Leukocyte Biology
• 影响因子: 5.5
• 作者: Arndt B;Kalinski T;Reinhold D;Thielitz A;Roessner A;Schraven B;Simeoni L
• 通讯作者: Simeoni L