T CELL RECEPTOR SIGNALING BY PHOSPHORYLATED FORMS OF TCR

T 细胞受体信号传导（磷酸化 TCR 形式）

• 批准号: 6632001
• 负责人: NICOLAI Stanislas Cyrille VAN OERS
• 金额: $ 23.94万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6632001
• 关键词: T cell receptor; T lymphocyte; anergy; biological signal transduction; cell differentiation; genetically modified animals; laboratory mouse; leukocyte activation /transformation; molecular cloning; phosphorylation; protein isoforms; protein sequence

DESCRIPTION (Adapted from Investigator's Abstract): The T cell receptor (TCR) zeta subunit, a component of the TCR complex, plays a critical role in TCR-mediated signal transduction. Following TCR engagement, the TCR-zeta subunit is phosphorylated on multiple tyrosine residues, resulting in the formation of two phosphorylated forms of 21 and 23 kDa. Recent studies have provided correlative evidence that the specific types of TCR zeta forms differ in their ability to couple to downstream effector molecules. Such differences are proposed to influence the processes of T cell development, the types of cytokines secreted by the T cells, and contribute to T cell anergy. The overall goal of this proposal is to understand how the formation of the 21 and 23 kDa phosphorylated species of the TCR zeta subunit affects TCR-mediated responses. The functional contribution of these phosphorylated forms of TCR zeta will be determined by selectively eliminating the formation of one or the other form in T cells and assessing the effects of these modifications on T cell development, TCR-mediated signal transduction, and T cell energy induction. Characterizing the regulation of TCR zeta phosphorylation, ZAP-70 recruitment and activation, and the interaction of the 21 and 23 kDa phosphorylated forms of TCR zeta with additional effector molecules is vital to our understanding of how these phosphorylated forms function during normal and pathological processes. The information derived from the proposed studies will have implications in regulating immune responses during T cell development, autoimmune diseases, allergic responses, and viral modulation of immune cells.

描述（改编自研究者摘要）：T细胞受体 (TCR)zeta亚单位是TCR复合物的一个组成部分，在TCR复合物的形成中起着关键作用。 在TCR介导的信号转导中的作用。在TCR参与后， TCR-ζ亚基在多个酪氨酸残基上磷酸化， 导致形成21和23 kDa的两种磷酸化形式。 最近的研究提供了相关的证据， 不同类型的TCR ζ形式在它们与下游细胞偶联的能力上不同， 效应分子这种差异被认为是影响 T细胞发育的过程，T细胞分泌的细胞因子的类型， T细胞，并有助于T细胞无反应性。这个项目的总体目标是 建议是了解21和23 kDa的形成， TCR ζ亚基的磷酸化种类影响TCR介导的免疫应答。 应答这些磷酸化形式的功能贡献， TCR ζ将通过选择性地消除TCR ζ的形成来确定。 T细胞中的一种或另一种形式，并评估这些 对T细胞发育的修饰，TCR介导的信号转导， 和T细胞能量诱导。表征TCR ζ的调节 磷酸化，ZAP-70募集和激活，以及相互作用 21和23 kDa磷酸化形式的TCR ζ与额外的 效应分子对于我们理解这些 磷酸化形式在正常和病理过程中发挥作用。 从拟议的研究中获得的信息将产生影响 在调节T细胞发育过程中的免疫反应， 疾病、过敏反应和免疫细胞的病毒调节。