Kawabata H, Germain R S, Ikezoe T, Tong X, Green E M, Gombart A F, Koeffler H P
Division of Hematology/Oncology, Department of Medicine, Burns and Allen Research Institute, Cedars-Sinai Medical Center, University of California Los Angeles School of Medicine, USA.
Blood. 2001 Sep 15;98(6):1949-54. doi: 10.1182/blood.v98.6.1949.
Complementary and genomic DNA for the murine transferrin receptor 2 (TfR2) were cloned and mapped to chromosome 5. Northern blot analysis showed that high levels of expression of murine TfR2 occurred in the liver, whereas expression of TfR1 in the liver was relatively low. During liver development, TfR2 was up-regulated and TfR1 was down-regulated. During erythrocytic differentiation of murine erythroleukemia (MEL) cells induced by dimethylsulfoxide, expression of TfR1 increased, whereas TfR2 decreased. In MEL cells, expression of TfR1 was induced by desferrioxamine, an iron chelator, and it was reduced by ferric nitrate. In contrast, levels of TfR2 were not affected by the cellular iron status. Reporter assay showed that GATA-1, an erythroid-specific transcription factor essential for erythrocytic differentiation at relatively early stages, enhanced TfR2 promoter activity. Interestingly, FOG-1, a cofactor of GATA-1 required for erythrocyte maturation, repressed the enhancement of the activity by GATA-1. Also, CCAAT-enhancer binding protein, which is abundant in liver, enhanced the promoter activity. Thus, tissue distribution of TfR2 was consistent with the reporter assays. Expression profiles of TfR2 were different from those of TfR1, suggesting unique functions for TfR2, which may be involved in iron metabolism, hepatocyte function, and erythrocytic differentiation.
克隆了小鼠转铁蛋白受体2（TfR2）的互补DNA和基因组DNA，并将其定位到5号染色体上。Northern印迹分析表明，小鼠TfR2在肝脏中高水平表达，而肝脏中TfR1的表达相对较低。在肝脏发育过程中，TfR2上调，TfR1下调。在二甲基亚砜诱导的小鼠红白血病（MEL）细胞的红细胞分化过程中，TfR1的表达增加，而TfR2减少。在MEL细胞中，铁螯合剂去铁胺可诱导TfR1的表达，而硝酸铁可使其表达降低。相反，TfR2的水平不受细胞铁状态的影响。报告基因检测表明，GATA-1是早期红细胞分化所必需的红细胞特异性转录因子，可增强TfR2启动子活性。有趣的是，FOG-1是红细胞成熟所需的GATA-1辅因子，可抑制GATA-1对活性的增强作用。此外，在肝脏中丰富的CCAAT增强子结合蛋白可增强启动子活性。因此，TfR2的组织分布与报告基因检测结果一致。TfR2的表达谱与TfR1不同，提示TfR2具有独特功能，可能参与铁代谢、肝细胞功能和红细胞分化。
