ERYTHROPOIETIN RECEPTOR AND ITS GENETIC CONTROL IN RED CELL DEVELOPMENT

促红细胞生成素是一种由肾脏合成的糖蛋白， 红细胞生成调节剂，可刺激成红细胞增殖 和差异化。红细胞生成素的克隆为 重组激素的生产，并已用于治疗 肾衰竭的贫血患者。关于这一点，我们所知甚少。 促红细胞生成素受体，最近已从 小鼠红白血病细胞。我们已经分离出一个基因克隆， 人促红细胞生成素受体来自人胎盘文库， 来自鼠促红细胞生成素受体5 '编码区的400 bp探针 cDNA。促红细胞生成素受体基因包含在基因组14kb内， 插入λ噬菌体载体的DNA。编码区位于 在约6kb内，并被几个间插序列中断 大小从79bp到1kb不等。插入序列富含 相关序列。编码区的部分序列分析表明， 使我们能够合成几种寡核苷酸引物， 在从OMC 1细胞制备的cDNA产生PCR片段中， 具有高水平促红细胞生成素受体的红白血病细胞系 在它的表面。随着人类促红细胞生成素基因组的克隆 受体，现在将有可能研究转录控制的 促红细胞生成素受体，其与促红细胞生成素的特异性结合， 促红细胞生成素与细胞结合后的信号转导过程 面

Erythropoietin, a glycoprotein synthesized by the kidney , is the primary regulator of erythropoiesis and can stimulate erythroblast proliferation and differentiation. The cloning of erythropoietin has led to the way for production of the recombinant hormone and has been useful for the treatment of anemic patients with kidney failure. Less is known about the erythropoietin receptor which has been recently cloned from the mRNA of murine erythroleukemia cells. We I have isolated a genomic clone containing the human erythropoietin receptor from a human placental library using a 400 bp probe from the 5'coding region of the murine erythropoietin receptor cDNA. The erythropoietin receptor gene is contained within 14 kb of genomic DNA inserted into a lambda phage vector. The coding region is localized within about 6 kb and is interrupted by several intervening sequences ranging in size from 79 bp to I kb. The intervening sequences are rich in Alu-related sequences. Partial sequence analysis of the coding region has enabled us to synthesize several oligonucleotide primers which were useful in generating PCR fragments from cDNA prepared from OMC1 cells, a human erythroleukemia cell line with high levels of the erythropoietin receptor on its surface. With the cloning of the genomic human erythropoietin receptor, it will now possible to study the transcriptional control of the erythropoietin receptor, its specific binding to erythropoietin and the process of signal transduction upon binding of erythropoietin at the cell surface.