LPS REGULATION OF MACROPHAGE FUNCTION

蛋白激酶C(PKC)诱导的磷酸化是必需的 巨噬细胞对细菌脂多糖(LPS)有反应。这个 本项目的目的是研究内毒素的作用机制 影响PKC依赖的信号通路，如那些导致 与吞噬有关的细胞骨架重排，膜 通信量、蜂窝粘附性和移动性。Aderem博士的重点是 Marcks蛋白的分子特征及内毒素诱导的PKC 底物，它调节细胞膜上的肌动蛋白结构。他会的 从功能上删除小鼠Marcks Null小鼠。在另一种方法中， 巨噬细胞特异性启动子Marcks在体内的作用(S)的确定 将用于产生表达突变Marcks的转基因小鼠 巨噬细胞中的蛋白质。他将描述内毒素诱导的马克的特征 通过定义5‘上游区域的调控元件来启动。这个 内含子和3‘非翻译区也将被分析 监管要素的存在。Marcks打靶的机制 将通过生物物理技术进行分析，并通过 Marcks结合蛋白的特性。马克在电影中的角色 将定义吞噬作用、溶酶体募集和细胞转运。 使用Marcks突变体和修改吞噬细胞途径的微生物。 他将通过研究来描述Marcks在细胞运动中的作用 肌动蛋白的结构和动力学、钙调蛋白与极化膜 表达Marcks突变体的插入、静止细胞。一部50 kDa的小说 巨噬细胞吞噬过程中诱导的蛋白质， 与吞噬小体相关，也将被描述为。

Protein kinase C (PKC)- induced phosphorylation is necessary for macrophages to respondfully to bacterial lipopolysaccharides (LPS). The aim of this project is to investigate the mechanism by which LPS influences PKC-dependent signalling pathways such as those leading to the cytoskeletal rearrangements associated with phagocytosis, membrane traffic, cellular adherence and motility. Dr. Aderem's focus is the molecular characterization of the MARCKS protein, and LPS-inducible PKC substrate, which regulates actin structure at the membrane. He will functionally delete the murine MARCKS null mice. In another approach to determining the role(s) of MARCKS in vivo, a macrophage-specific promoter will be used to generate transgenic mice expressing mutant MARCKS proteins in macrophages. He will characterize the LPS- inducible MARCKS promoter by defining regulatory elements in the 5' upstream region. The intron and the 3' untranslated region will also be analyzed for the presence of regulatory elements. The mechanism by which MARCKS targets to specific membranes will be analyzed by biophysical techniques, and by characterizing MARCKS binding proteins. The role of MARCKS in phagocytosis, lysosome recruitment, and transcytosis will be defined using MARCKS mutants and microbes which modify the phagocytic pathway. He will characterize the role of MARCKS in cell motility by examining actin structure and dynamics, calmodulin, and polarized membrane insertion, immotile cells expressing MARCKS mutants. A novel 50 kDa protein which is induced during phagocytosis in macrophages, and which associates with phagosomes, will also be characterized.