Role of Pactolus in the innate immune response

Pactolus 在先天免疫反应中的作用

• 批准号: 6631980
• 负责人: John Weis
• 金额: $ 33.75万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6631980
• 关键词: RNA splicing; cell adhesion; cell adhesion molecules; cell migration; cellular immunity; gene induction /repression; genetically modified animals; immunogenetics; laboratory mouse; laboratory rabbit; laboratory rat; leukocyte activation /transformation; neutrophil; protein structure function

DESCRIPTION (provided by applicant): The mechanism of cell adhesion takes on special significance in studies of the immune response due to the unique nature of the primary constituents of the response, circulating cells. Most organ systems are comprised of cells whose position within that tissue is fixed during differentiation. Alternatively, the immune organ system consists of cells types that are continually being derived de novo from bone marrow precursors and must seek out selected sites within the body for their specific functions. We have isolated a novel gene, dubbed Pactolus that is related to the family of B integrins. This gene was first isolated due to its selective expression in maturing connective tissue mast cells compared to mucosal mast cells. Subsequently we have found that the major cell of the animal that produces Pactolus is the maturing and mature neutrophil. The Pactolus protein is found in two primary configurations: truncated and membrane bound. Upon neutrophil activation, the truncated form is secreted into the supernatant. Additionally, the cell surface expression of the protein is also increased after activation due to the mobilization of intracellular stores. This protein, which by structural analogy must be an adhesion receptor, thus has the potential to bind directly to its ligand with either a cell bound or soluble form. This application proposes to define the function of the Pactolus protein within the cell and the animal by developing a series of approaches to study the cell biology of Pactolus, to analyze its function via the analysis of already created Pactolus knockout animals, and to further our understanding of the transcriptional control of the gene. Understanding its transcriptional control is especially intriguing since production of the protein in inappropriate cells (lymphocytes, etc) leads to cell death. By following the detailed experimental plan of this application, the role of this very interesting and surprising protein in the immune response of the animal will be elucidated

描述（由申请人提供）：细胞粘附的机理 由于独特的性质而导致免疫反应的研究特殊意义 反应的主要成分，循环细胞。大多数器官 系统由其在该组织中的位置固定的细胞组成 在分化过程中。或者，免疫器官系统包括 细胞类型不断从骨髓派生。 前体，必须为其特定而在体内选出选定的位置 功能。 我们隔离了一个新型基因，称为帕托鲁斯，与家族有关 B整合素。该基因首先是由于其选择性表达在 与粘膜肥大细胞相比，成熟的结缔组织肥大细胞。 随后，我们发现产生动物的主要细胞 Pactolus是成熟和成熟的中性粒细胞。发现Pactolus蛋白 在两种主要配置中：截短和膜结合。在中性粒细胞上 激活，将截短的形式分泌到上清液中。此外， 激活后，蛋白质的细胞表面表达也会增加 由于细胞内存储的动员。这种蛋白质，通过 结构类比必须是粘附受体，因此具有结合的潜力 直接使用具有绑定或可溶性形式的细胞或可溶性形式的配体。 该应用建议在内部定义Pactolus蛋白的功能 细胞和动物通过开发一系列研究细胞的方法 Pactolus的生物学，通过分析已经分析其功能 创建了帕托鲁斯淘汰动物，以进一步了解我们对 基因的转录控制。了解其转录控制 自从不适当细胞中蛋白质的产生以来，特别有趣 （淋巴细胞等）导致细胞死亡。通过遵循详细的实验 该应用程序的计划，这个非常有趣和令人惊讶的作用 将阐明动物免疫反应中的蛋白质