HUMAN CELL SURFACE ANTIGENS: TRANSFERRIN RECEPTORS

人类细胞表面抗原：转铁蛋白受体

• 批准号: 3172610
• 负责人: IAN S TROWBRIDGE
• 金额: $ 18.43万
• 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/3172610
• 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