MEMBRANE PROTEIN TRAFFIC IN NORMAL AND TRANSFORMED CELLS

正常细胞和转化细胞中的膜蛋白运输

• 批准号: 3094195
• 负责人: JAMES Douglas JAMIESON
• 金额: $ 117.25万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-05-01 至 1993-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3094195
• 关键词: membrane proteins; neoplastic transformation; protein transport

The overall goal of this Program Project is to understand the molecular mechanisms involved in the control of protein and membrane traffic in normal and transformed cells. It consists of seven individual projects: Project 1: The goal of this project is to characterize Golgi subcompartments and to identify functionally important membrane proteins found in these subcompartments. The trafficking of the lysosomal Man-6-P receptor (46 Kd) through Golgi subcompartments will also be investigated in normal and transformed cells. Project 2: This project takes advantage of the genetic approach and the availability of mutants defective in specific steps along the secretory pathway to identify proteins or regions of proteins that are important in targeting along the exocytic pathway. One such mutant to be investigated has a defective gene that appears to be a member of the ras oncogene family. Project 3: The goal of this project is to investigate the role of protein conformation on signaling transport along the secretory pathway using viral membrane proteins as models. Project 4: This project will investigate the role of the binding protein BiP in post-translational processing and ER to Golgi transit of nascent secretory and membrane proteins in normal and transformed cells. Project 5: The purpose of this project is to determine the mechanisms of sorting and traffic control during endocytosis using closely related Fc receptors in normal and transformed cells expressing this receptor from clone cDNAs. Project 6: The goals of this project are to define the molecular basis for the transient failure of the membrane protein, glycophorin, to be segregated in the ER in transformed Friend Erytholeukemic cells, and to attempt to identify sorter proteins and carrier proteins involved in control of vesicular membrane traffic. Project 7: Hybrid proteins generated by gene fusion and expression technologies have been shown to be blocked at various steps along the biosynthetic pathway. In this project the precise site of the blockage and the molecular features responsible for the blockages will be investigated.

本计划项目的总体目标是了解 参与蛋白质控制的分子机制， 正常和转化细胞的膜运输。 它包括 七个项目： 项目1：本项目的目标是描述高尔基体的特征 亚隔室，并确定功能重要 在这些亚区室中发现的膜蛋白。 的 溶酶体Man-6-P受体（46 Kd）通过 高尔基体亚室也将在正常和 转化细胞 项目2：该项目利用遗传方法 和突变体的可用性缺陷在特定步骤沿着 分泌途径来鉴定蛋白质或蛋白质区域 在靶向沿着胞外途径中很重要。 一 这些待研究突变体具有缺陷基因， 是ras癌基因家族的一员。 项目3：本项目的目标是调查 蛋白质构象对信号转导沿着分泌 使用病毒膜蛋白作为模型的途径。 项目4：本项目将研究绑定的作用 翻译后加工中的BiP蛋白和高尔基体的ER 新生分泌和膜蛋白在正常和 转化细胞 项目5：该项目的目的是确定 内吞作用中的分选和运输控制机制 正常和转化细胞中密切相关的Fc受体 从克隆cDNA中表达该受体。 项目6：该项目的目标是定义分子 膜蛋白瞬时失效的基础， 血型糖蛋白，在转化的朋友的ER中分离 红白血病细胞，并试图确定分选蛋白 以及参与控制囊泡膜的载体蛋白 交通 项目7：通过基因融合产生的杂交蛋白， 表达技术已被证明在各种不同的情况下被阻断， 沿着生物合成途径。 在这个项目中， 堵塞的部位和负责的分子特征 将对堵塞情况进行调查。