Zon L I, Moreau J F, Koo J W, Mathey-Prevot B, D'Andrea A D
Department of Pediatrics, Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Mol Cell Biol. 1992 Jul;12(7):2949-57. doi: 10.1128/mcb.12.7.2949-2957.1992.
The erythropoietin receptor (EPO-R), a member of the cytokine receptor superfamily, can be activated by binding either erythropoietin (EPO) or gp55, the Friend spleen focus-forming virus glycoprotein. The highly specific interaction between gp55 and EPO-R triggers cell proliferation and thereby causes the first stage of Friend virus-induced erythroleukemia. We have generated functional chimeric receptors containing regions of the EPO-R and the interleukin-3 receptor (AIC2A polypeptide), a related cytokine receptor which does not interact with gp55. All chimeric receptors were expressed at similar levels, had similar binding affinities for EPO, and conferred EPO-dependent cell growth. Only those chimeric receptors which contained the EPO-R transmembrane region were activated by gp55. These results demonstrate that the transmembrane region of the EPO-R is critical for activation by gp55. In addition, analysis of a soluble, secreted EPO-R and cysteine point mutants of the EPO-R show that the extracytoplasmic region of the EPO-R specifically interacts with gp55.
促红细胞生成素受体（EPO-R）是细胞因子受体超家族的成员之一，可通过与促红细胞生成素（EPO）或gp55（弗氏脾脏灶形成病毒糖蛋白）结合而被激活。gp55与EPO-R之间高度特异性的相互作用触发细胞增殖，从而引发弗氏病毒诱导的红细胞白血病的第一阶段。我们构建了功能性嵌合受体，其包含EPO-R的区域和白细胞介素-3受体（AIC2A多肽）的区域，白细胞介素-3受体是一种不与gp55相互作用的相关细胞因子受体。所有嵌合受体均以相似水平表达，对EPO具有相似的结合亲和力，并赋予细胞依赖EPO生长的特性。只有那些包含EPO-R跨膜区域的嵌合受体能被gp55激活。这些结果表明，EPO-R的跨膜区域对于gp55激活至关重要。此外，对可溶性、分泌型EPO-R以及EPO-R的半胱氨酸点突变体的分析表明，EPO-R的胞外区域与gp55特异性相互作用。
