IMMUNOLOGY ACTIVATED ENZYME SYSTEMS OF CELLS

免疫学激活细胞酶系统

• 批准号: 3124597
• 负责人: ELMER L BECKER
• 金额: $ 16万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-30 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3124597
• 关键词: G protein; calcium flux; cell free system; chemotaxis; computer graphics /printing; enzyme mechanism; esterase; exocytosis; granule; human subject; laboratory rabbit; leukocyte activation /transformation; mitogens; neutrophil; phosphorylation; protein kinase C; protein structure; receptor; receptor binding; synthetic peptide

The long term objectives of this application are to define in molecular terms the biochemical and physiological responses of the neutrophil to chemotactic agents. In this work, particular stress is laid upon delineating the nature and role of the formylpeptide chemotactic receptor of the neutrophil but there is also a broadening of the long term objectives to include the study of the terminal mechanisms of neutrophil granule exocytosis. The initial aim is to extend and refine the model of the formylpeptide receptor of the rabbit neutrophil to the area of accommodating a terra, pentapeptides and also longer chain peptides. In addition, particular attention will be paid to the nature of the conformation of the peptide in the receptor using computer simulation to guide the research. In this regard also, the basis for the high activity of the unformulated defivatives of the pentapeptides we have studied will also be investigated. The second aim is to study the nature and mechanism of the release of the specific granule contents in cell free extracts of rabbit peritoneal neutrophils and attempt to extend these studies to the release from azurophil granules and to release engendered by fMet-Leu-Phe-OH stimulation of receptors present in the cell free neutrophil system. The third aim is to test the hypothesis that prior incubation with phorbol 12-myristate 13-acetate (PMA) induces inhibition of neutrophil responses to fMet-Le-phe and other chemotactic factors by activating protein kinase C to phosphorylate the alpha n subunit of Gn the G protein that mediates the stimulated receptor activation of phospholipase C. The putative phosphorylation causes a shift in the equilibrium between alpha n and beta gamma to the undissociated heterotrimer Gn and a loss of Gn function.

该应用的长期目标是在分子中定义 术语中性粒细胞的生化和生理反应 趋化剂。 在这项工作中，特别压力 描述甲基肽趋化受体的性质和作用 嗜中性粒细胞，但也有长期的拓宽 目的包括研究中性粒细胞的末端机制 颗粒胞吐作用。 最初的目的是扩展和完善 兔嗜中性粒细胞的甲基肽受体到该面积 容纳甲虫，五肽和更长的链肽。 在 此外，将特别关注 使用计算机模拟到受体中肽的构象 指导研究。 在这方面，高活动的基础 我们研究过的五肽的未形成的缺陷 也可以调查。 第二个目的是研究性质和 释放特定颗粒含量在无细胞中的机制 兔腹膜中性粒细胞的提取物，并试图扩展这些 研究从Azurophil颗粒中发布并释放出来的 通过FMET-LEU-PHE-OH OH刺激受体中存在于细胞中的受体 中性粒细胞系统。第三个目的是检验以下假设 与佛波尔12-饱和13-乙酸盐（PMA）孵育可诱导抑制作用 中性粒细胞对FMET-LE-PHE和其他趋化因子的反应 激活蛋白激酶C磷酸化GN的αN亚基 介导刺激受体激活的G蛋白 磷脂酶C.推定的磷酸化导致 alpha n和beta伽马之间的平衡与未分离的 异三聚体GN和GN功能的丧失。