T CELL RECEPTOR SIGNALING BY PHOSPHORYLATED FORMS OF TCR

描述(摘自《研究人员摘要》)：T细胞受体 (TCR)Zeta亚基是TCR复合体的一个组成部分，它发挥着至关重要的作用 在TCR介导的信号转导中的作用。在TCR参与之后， TCR-Zeta亚基在多个酪氨酸残基上被磷酸化， 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证据，表明特定的 不同类型的TCR Zeta形式在连接下游的能力上有所不同 效应器分子。这种差异被认为是为了影响 T细胞的发育过程，T细胞分泌的细胞因子的类型 T细胞，并导致T细胞无能。这个项目的总体目标是 建议了解21和23 kDa是如何形成的 TCR Zeta亚基的磷酸化物种影响TCR介导的 回应。这些磷酸化形式的功能贡献 TCR Zeta将通过选择性地消除形成 T细胞中的一种或另一种形式并评估这些 T细胞发育的修饰，TCR介导的信号转导， T细胞能量诱导。TCR Zeta的调控特征 磷酸化、ZAP-70募集和激活及其相互作用 在21和23 kDa的TCR Zeta的磷酸化形式中 效应器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中，自身免疫 疾病、过敏反应和免疫细胞的病毒调节。

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.