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）：细胞粘附的机制表现为 由于其独特的性质， 反应的主要成分循环细胞。大多数器官 系统由细胞组成，细胞在组织中的位置是固定的 在分化过程中。或者，免疫器官系统包括 从骨髓中不断衍生的细胞类型 前体，必须在体内寻找特定的部位， 功能协调发展的 我们已经分离出一个新的基因，被称为Pactolus，它与 B整联蛋白。该基因首先由于其在大肠杆菌中的选择性表达而被分离出来。 与粘膜肥大细胞相比，成熟的结缔组织肥大细胞。 后来我们发现动物体内产生 Pactolus是成熟的中性粒细胞。Pactolus蛋白被发现 有两种主要构型：截短构型和膜结合构型。中性粒细胞 在活化后，截短形式分泌到上清液中。此外，本发明还 活化后蛋白质的细胞表面表达也增加 这是由于细胞内储存的动员。这种蛋白质， 结构类似物必须是粘附受体，因此具有结合的潜力 以细胞结合或可溶形式直接与其配体结合。 本申请提出定义Pactolus蛋白的功能， 通过开发一系列研究细胞的方法， Pactolus的生物学，通过分析其功能， 创造了Pactolus敲除动物，并进一步了解 基因的转录控制。了解其转录控制 特别有趣的是， （淋巴细胞等）导致细胞死亡。通过详细的实验， 这个应用程序的计划，这个角色非常有趣和令人惊讶 将阐明动物免疫应答中的蛋白质