HUMAN CELL SURFACE ANTIGENS: TRANSFERRIN RECEPTORS

人类细胞表面抗原：转铁蛋白受体

• 批准号: 3172609
• 负责人: IAN S TROWBRIDGE
• 金额: $ 18.34万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-06-01 至 1991-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3172609
• 关键词: chemical structure function; gene expression; genetic manipulation; genetic regulation; human tissue; laboratory mouse; laboratory rat; monoclonal antibody; mutant; neoplasm /cancer immunology; neoplastic growth; surface antigens; tissue /cell culture; transferrin; transferrin receptor

The transferrin receptor mediates cellular iron uptake via the iron-binding protein, transferrin, within the hematopoietic system and in other tissues. Monoclonal antibodies against the transferrin receptor can block receptor function and inhibit cell growth. The longterm objective of the proposed work is to understand the structure-function relationship of the transferrin receptor and its role in cell growth. This knowledge will contribute to related practical applications of monoclonal antibodies against the transferrin receptor and growth-related receptors in cancer and more effective methods of antibody-mediated drug targeting. As a continuation of previous structural and functional studies, it is proposed to prepare monoclonal antibodies of predetermined specificity that react with the human transferrin receptor to further define how antibodies block receptor function. Antibodies against the cytoplasmic domain of the transferrin receptor will be obtained and used to purify the intracellular membrane compartment enriched in transferrin receptors in order to learn more about the molecular basis of receptor trafficking within cells. As complementary approaches to understanding transferrin receptor function, in vitro mutagenesis will be used to modify the human transferrin receptor and the structural and functional consequences of the mutations analyzed, and efforts will be made to obtain sufficient amounts of transferrin receptor either in a bacterial expression system or by overexpression in mammalian cells to initiate X-ray crystallographic studies. Collaborative studies are proposed to characterize mutant mouse lymphoma cells resistant to killing by anti-transferrin receptor antibodies and ricin A-antibody conjugates and to investigate the regulation of transferrin receptor expression during the growth and differentiation of HL-60 cells.

转铁蛋白受体通过铁结合介导细胞铁摄取， 蛋白质，转铁蛋白，在造血系统和其他 组织中 抗转铁蛋白受体的单克隆抗体可以阻断 受体功能并抑制细胞生长。 长期目标 建议的工作是了解结构-功能关系的 转铁蛋白受体及其在细胞生长中的作用。 这些知识将 有助于单克隆抗体的相关实际应用 针对癌症中的转铁蛋白受体和生长相关受体， 更有效的抗体介导的药物靶向方法。 作为 继续以前的结构和功能研究，建议 为了制备具有预定特异性的单克隆抗体， 与人转铁蛋白受体进一步确定抗体如何阻断 受体功能 抗抗人巨噬细胞胞质结构域的抗体 转铁蛋白受体将被获得并用于纯化细胞内 富含转铁蛋白受体的膜室， 更多关于细胞内受体运输的分子基础。 作为 了解转铁蛋白受体功能的补充方法， 体外诱变将用于修饰人转铁蛋白受体， 分析的突变的结构和功能后果，以及 将努力获得足够量的转铁蛋白受体 在细菌表达系统中或通过在哺乳动物中过表达 细胞启动X射线晶体学研究。 合作研究 提出了表征突变小鼠淋巴瘤细胞耐药， 抗转铁蛋白受体抗体和蓖麻毒素A抗体的杀伤作用 偶联物，并研究转铁蛋白受体的调节 在HL-60细胞生长和分化过程中的表达。