Studies on the physiological functions of NFE-1 family as cell differentiation determinant

我们分析了GATA-1因子的生理功能。我们发现GATA-1基因被促红细胞生成素受体(EPOR)介导的信号激活，并且GATA-1反式激活EPOR基因的表达。因此，GATA-1是红系细胞的细胞谱系决定因素之一。EPOR介导的信号激活GATA-1基因的转录和翻译，进而刺激GATA-1蛋白的丝氨酸/苏氨酸磷酸化。在EPO与EPOR结合之前低水平表达的GATA-1似乎没有活性，但增强的和磷酸化的GATA-1蛋白具有反式激活珠蛋白、EPOR、Hox2家族和SCL基因的活性。SCL基因产物还能反式激活EPOR基因和珠蛋白基因。将EPOR基因导入IL-3依赖的BA/F3细胞，可使其红系表型表达，即GATA-1、scl和珠蛋白基因的转录和翻译被激活。此外，EPOR胞外区与IL2或IL3受体的跨膜区和胞内区构成的嵌合受体可以在BA/F3细胞中传递红系分化信号，表明EPOR胞外区在分化和生长信号的传递中是必不可少的。

We have analyzed the physiological function of GATA-1 factor. We found that GATA-1 gene is activated by erythropoietin (Epo) receptor (EpoR)-mediated signal, and that GATA-1 transactivates EpoR gene expression. Thus, GATA-1 is one of the cell lineage determinants of erythroid cells. EpoR-mediated signal activates transcription and translation of GATA-1 gene, and further stimulate serine/threonine phosphorylation of GATA-1 protein. GATA-1 which is expressed in low level before Epo binds to EpoR seems to be inactive, but the enhanced and phosphorylated GATA-1 protein is active to transactivate globin, EpoR, Hox2 family and SCL gene expression. SCL gene product was also found to transactivate EpoR gene as well as globin genes. Transfection of EpoR gene into IL3-dependent Ba/F3 cells resulted in erythroid phenotypic expression of this lymphoid cells, that is, activation of transcription and translation of GATA-1, SCl and globin genes. Furthermore, chimeric receptors constituted with extracellular domains of EpoR and transmembrane and cytoplasmic domains of IL2 or IL3 receptors could transmit erythroid differentiation signal in Ba/F3 cells, indicating that extracellular domains for EpoR is essential for transmission of differentiation as well as growth signals.