Antigen Binding, Crosslinking and Signaling

抗原结合、交联和信号传导

• 批准号: 6885775
• 负责人: DAVID A HOLOWKA
• 金额: $ 25.94万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-08-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6885775
• 关键词: B cell receptor; CHO cells; T cell receptor; antibody receptor; antigen receptors; biological signal transduction; cellular immunity; crosslink; exocytosis; flow cytometry; granulocyte; guanosinetriphosphatases; immunoglobulin E; mast cell; phosphorylation; protein tyrosine kinase; receptor binding; tissue /cell culture; western blottings

DESCRIPTION (provided by applicant): The proposed research addresses key unanswered questions about the structures and events by which antigen-activated immunoreceptors initiate cellular signaling leading to diverse responses. The high affinity receptor for lgE (FcepsilonRI) on RBL-2H3 mast cells serves as a valuable model system, and new experimental thrusts will build on previous extensive studies. Specific Aim #1 extends experiments with structurally defined ligands to extract critical features of ligand architecture and cross-linking mechanism that facilitate or inhibit signaling responses. Specific Aim #2 continues efforts to understand the molecular basis by which lipid rafts participate in FcepsilonRI signal initiation, and to achieve functional reconstitution of this receptor in model membranes from purified, defined components. Specific Aim #3 proposes real-time imaging studies to elucidate the process by which FcepsilonRI becomes segregated from particular lipid raft components, and investigate how plasma membrane locations for stimulated exocytosis are determined. Specific Aim #4 proposes experiments to understand the mechanisms by which Rho family proteins and other low molecular weight GTPases participate in early FcepsilonRI signaling, as revealed by previous studies with mutant RBL-B6A4C1 mast cells. These investigations integrate diverse physical, chemical, and biological approaches to provide novel insights into the structure and molecular mechanisms of IgE-FcepsilonRI signaling, and they will advance our molecular understanding of the cell biology of this important immune cell prototype.

描述（由申请人提供）：拟议的研究解决了有关抗原激活的免疫受体启动细胞信号导致各种反应的结构和事件的关键未解决问题。 RBL-2H3肥大细胞上LGE（FCEPSILONRI）的高亲和力受体是有价值的模型系统，而新的实验推力将基于先前的广泛研究。特定的目标＃1扩展了具有结构定义的配体的实验，以提取配体结构的关键特征和促进或抑制信号反应的交联机制。特定目标＃2继续努力了解脂质筏参与Fcepsilonri信号启动的分子基础，并从纯化的，定义的成分中实现该受体的功能重构。特定目标＃3提出了实时成像研究，以阐明fcepsilonri从特定的脂质筏成分隔离的过程，并研究如何确定刺激胞吐作用的质膜位置。特定目的＃4提出了实验，以了解Rho家族蛋白和其他低分子量GTPases参与早期Fcepsilonri信号传导的机制，如先前对突变RBL RBL-B6A4C1肥大细胞的研究所表明的那样。这些研究整合了多样化的物理，化学和生物学方法，以提供有关IGE-FCEPSILONRI信号的结构和分子机制的新见解，它们将提高我们对这一重要免疫细胞原型细胞生物学的分子理解。