HUMAN CELL SURFACE ANTIGENS: TRANSFERRIN RECEPTORS

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，在造血系统内和其他 纸巾。抗转铁蛋白受体的单抗可以阻断 受体的功能和抑制细胞生长。该计划的长期目标是 提出的工作是理解结构与功能的关系 转铁蛋白受体及其在细胞生长中的作用。这一知识将会 有助于单抗的相关实际应用 抗转铁蛋白受体和生长相关受体在癌症和 更有效的抗体介导的药物靶向方法。作为一名 继续以前的结构和功能研究，建议 制备具有预先确定的特异性的单抗 用人类转铁蛋白受体进一步确定抗体如何阻断 受体功能。抗猪瘟病毒胞浆结构域抗体 将获得转铁蛋白受体并用于纯化细胞内 富含转铁蛋白受体的膜室为了学习 更多关于受体在细胞内运输的分子基础。AS 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和 所分析的突变的结构和功能后果，以及 将努力获得足够数量的转铁蛋白受体 在细菌表达系统中或在哺乳动物中过表达 细胞启动X射线结晶学研究。合作研究 被建议用来表征突变的小鼠淋巴瘤细胞对 抗转铁蛋白受体抗体和蓖麻毒素A抗体的杀伤作用 结合物和转铁蛋白受体的调节作用 在HL-60细胞生长和分化过程中的表达。

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.