Receptor Aggregation and Its Effects

受体聚集及其影响

基本信息

批准号：
7288798
负责人：
BYRON B GOLDSTEIN
金额：
$ 62.63万
依托单位：
LOS ALAMOS NAT SECTY-LOS ALAMOS NAT LAB
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-04-01 至 2008-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7288798
关键词：
Affinity Allergic Reaction Amino Acid Sequence Basophils Binding Binding Proteins Binding Sites Biochemical C-terminal CD3 Antigens Calcium Cell Degranulation Cells Collaborations Complex Condition Cytokine Receptors Cytoplasmic Tail Data Diffuse Docking Environment Event Extracellular Domain Family Goals Grant Growth Factor Receptors Health ITAM IgE IgE Receptors IgG Receptors Immune Interleukin 2 Receptor Kinetics Laboratories Ligand Binding Ligands Mediating Modeling Modification PTPRC gene Pathway interactions Phosphorylation Phosphotransferases Phosphotyrosine Play Positioning Attribute Property Protein Tyrosine Kinase Protein Tyrosine Phosphatase Proteins Range Receptor Aggregation Receptor Cell Receptor Protein-Tyrosine Kinases Receptor Signaling Recruitment Activity Regulation Role Scaffolding Protein Series Signal Pathway Signal Transduction Signaling Molecule Site Surface System T-Cell Activation T-Lymphocyte Testing Time Transmembrane Domain Tyrosine Work adapter protein base computerized data processing crosslink dacron design dimer human INPPL1 protein inositol-1,4,5-trisphosphate 5-phosphatase lyn protein-tyrosine kinase mast cell mathematical model member predictive modeling receptor receptor binding release of sequestered calcium ion into cytoplasm research study response size src Homology Region 2 Domain src-Family Kinases

项目摘要

DESCRIPTION (provided by applicant): 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. The project focuses on the high affinity receptor for IgE, FcepsilonRI, an MIRR that plays a key role in allergic reactions. A major goal of this project is to build and test detailed models of the early events of cell signaling mediated by this receptor. The mathematical models will be used to analyze experimental data, determine parameter values, design new experiments and test ideas about the roles of specific signaling molecules and their subunits. Mathematical models of signaling cascades are analogous to stable transfectants. In both the model and the transfectant, a small subset of the molecules that participate in the signal cascade are selected for study. The role of both the model and the transfectant is to understand how the selected molecules interact with each other. Components of the initial model, which has been tested extensively and found to be consistent with available data, are the beta and gamma subunits of FcepsilonRI and the tyrosine kinases Lyn and Syk. This model provides the basis for several proposed extensions. The next molecule in the activation pathway, which an extended model will incorporate, is the transmembrane scaffold protein LAT (linker for activation of T cells). Another extension will consider an inhibitory mechanism. Under many conditions the co-aggregation of an MIRR with an inhibitory receptor, FcepsilonRI IIB, reduces cellular responses. Such co-aggregation may be involved in the damping of allergic reactions. The model developed to study FcepsilonRI mediated signaling will be extended to study the inhibitory events triggered by FcepsilonRI - FcgammaRIIB coaggregation. Additional components of the extended model will be FcgammaRIIB, the inositol phosphatase SHIP1, and the cytosolic adapter protein Grb2. The studies in this project are health related, bearing on allergic reactions and their treatment.

描述（由申请人提供）：移动受体在单元表面扩散，使其能够感知其环境并响应它。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外部配体的捕获至关重要，对于打开或关闭细胞反应的强制性和强制性。该项目着重于IgE的高亲和力受体Fcepsilonri，这是一个在过敏反应中起关键作用的MIRR。该项目的一个主要目标是构建和测试该受体介导的细胞信号的早期事件的详细模型。数学模型将用于分析实验数据，确定参数值，设计新的实验和测试思想，以了解特定信号分子及其亚基的作用。信号级联的数学模型类似于稳定的转染剂。在模型和转让剂中，选择参与信号级联的一小部分进行研究。模型和转染剂的作用是了解所选分子如何相互相互作用。初始模型的组成部分已经进行了广泛的测试并发现与可用数据一致，是Fcepsilonri的β和伽马亚基和酪氨酸激酶Lyn和Syk。该模型为几个提出的扩展范围提供了基础。扩展模型将结合的激活途径中的下一个分子是跨膜支架蛋白LAT（T细胞激活的链接）。另一个扩展将考虑一种抑制机制。在许多条件下，MIRR与抑制性受体fcepsilonri iib共同聚集会减少细胞反应。这种共聚集可能与过敏反应的阻尼有关。为研究Fcepsilonri介导的信号传导而开发的模型将扩展，以研究由fcepsilonri -fcgammariib凝集触发的抑制事件。扩展模型的其他组件将是fcgammariib，肌醇磷酸酶Ship1和胞质衔接蛋白GRB2。该项目的研究与健康有关，涉及过敏反应及其治疗。