Genetische Analyse des Mechanismus der ubiquitinilierungsabhängigen Kontrolle der Signaltransduktion durch den T-Zell Rezeptor (The genetic analysis of the mechanism of the ubiquitination-dependent control of T cell receptor signalling)

T细胞受体信号传导泛素化依赖性控制信号转导机制的遗传分析

• 批准号: 5106079
• 负责人: Professor Dr. Alexander Tarakhovsky
• 金额: --
• 依托单位: Laboratory of Lymphocyte Signaling
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 1998
• 资助国家: 德国
• 起止时间: 1997-12-31 至 2002-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5106079?language=en
• 关键词: Genetische; Analyse; des; Mechanismus; der

The development and activation of T cells is governed by signals derived from T cell antigen receptor. Binding of the MHCpeptide ligands to TCR and CD4 or CD8 co-receptors induces the activation of src-family protein tyrosine kinase (src-PTK) followed by assembly of the functional TCR-dependent signal transducing chain. The strength of the TCR dependent signal is largely detemined by the surface expression levels of TCR-CD3 signalling complex and intracellular expression levels of src-PTK Lck and Fyn. Binding of the MHC-peptide ligand to TCR is followed by ubiquitination and down-regulation of TCR-CD3 and srcPTKs. This process is supposed to play an important role in setting up the threshold for T cell activation at levels preventing the hyperactivation of T cells. The mechanisms of ligand-induced ubiquitination of TCR and src-PTKs are poorly understood. The aim of the proposed project is to understand the mechanism of ubiquitination of TCR-CD3 and src-PTK and the role of this process in T cell activation and development.

T细胞的发育和活化受来自T细胞抗原受体的信号支配。MHC肽配体与TCR和CD 4或CD 8共受体的结合诱导src家族蛋白酪氨酸激酶（src-PTK）的活化，随后组装功能性TCR依赖性信号转导链。TCR依赖性信号的强度在很大程度上由TCR-CD 3信号传导复合物的表面表达水平和src-PTK Lck和Fyn的细胞内表达水平决定。MHC-肽配体与TCR的结合之后是TCR-CD 3和srcPTK的泛素化和下调。这一过程被认为在建立T细胞活化阈值以防止T细胞过度活化方面发挥重要作用。配体诱导TCR和src-PTKs泛素化的机制知之甚少。该项目的目的是了解TCR-CD 3和Src-PTK的泛素化机制以及该过程在T细胞活化和发育中的作用。