RECEPTOR AGGREGATION AND ITS EFFECTS

受体聚集及其影响

• 批准号: 6332281
• 负责人: BYRON B GOLDSTEIN
• 金额: $ 11.89万
• 依托单位: UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-04-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6332281
• 关键词: antibody receptor; basophils; biological signal transduction; biophysics; biosensor device; cytokine receptors; immunoglobulin E; interleukin 2; ligands; mathematical model; model design /development; protein tyrosine kinase; receptor binding

DESCRIPTION (Adapted from Investigator's Abstract): Mobile receptors diffusing over the surface of a cell allow it to sense its environment and respond to it. For many types of receptors, including the multisubunit immune recognition receptors (MIRR), aggregation of these receptors is crucial for the capture of external ligands and mandatory for the turning on or off of cellular responses. This project aims to understand the underlying physical chemistry of receptor aggregation, to use this understanding to develop mathematical models that can predict the time course of aggregate formation, and to relate aggregation states to specific cellular responses. It then aims to construct and test detailed mathematical models of the early events of cell signaling that are initiated when a ligand induces receptors to aggregate. The high affinity receptor for IgE, FceRI, expressed on basophils and stable transfectants, is the model system that will be used to study signaling mediated by MIRR. The mathematical models will be used to analyze experimental data; determine parameter values; design new experiments; and test ideas about the roles of the beta and gamma subunits of the receptor, and the tyrosine kinases Lyn and Syk. Cytokines induce receptor aggregation in a quite different way than the MIRR. The interaction of IL-2 with its receptor subunits will be studied using novel soluble multichain constructs. Estimates of rate constants for both receptor systems will be obtained from binding studies using the BIAcore biosensor. An aim of this project is to develop methods to use the BlAcore to study ligand-induced receptor aggregation. The studies in this project are health related, bearing on allergic reactions and their treatment as well as other aspects of the immune response.

描述（根据研究者的摘要改编）：移动受体扩散 在细胞的表面上，它可以感知其环境并响应环境。 对于许多类型的受体，包括多亚基免疫识别 受体（MIRR），这些受体的聚集对于捕获至关重要 外部配体和强制性，用于打开或关闭细胞反应。 该项目旨在了解受体的潜在物理化学反应 聚集，利用这种理解来开发可以 预测汇总形成的时间过程，并关联聚合 对特定的细胞反应状态。然后，它旨在构建和测试 细胞信号的早期事件的详细数学模型是 当配体诱导受体聚集时开始。高亲和力 在嗜碱性粒细胞和稳定转染剂上表达的IgE，FCERI的受体，是 将用于研究由MIRR介导的信号传导的模型系统。 数学模型将用于分析实验数据。决定 参数值；设计新实验；并测试有关角色的想法 受体的β和伽马亚基，以及酪氨酸激酶林和Syk。 细胞因子以与MIRR完全不同的方式诱导受体聚集。 IL-2与其受体亚基的相互作用将使用新颖 可溶性多键结构。两个受体的速率常数估计值 使用Biacore生物传感器将从结合研究中获得系统。一个 该项目的目的是开发使用Blacore学习的方法 配体诱导的受体聚集。该项目的研究是健康 相关，与过敏反应及其治疗以及其他有关 免疫反应的各个方面。