Yoshimura A, Longmore G, Lodish H F
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts.
Nature. 1990 Dec 13;348(6302):647-9. doi: 10.1038/348647a0.
The receptors for erythropoietin and other cytokines constitute a new superfamily. They have no tyrosine-kinase or other enzyme motif and their signal-transducing mechanism is unclear. Here we describe two classes of activating mutations in the erythropoietin receptor (EPOR). A single point mutation in the exoplasmic domain enables it to induce hormone-independent cell growth and tumorigenesis after expression in nontumorigenic, interleukin-3-dependent haematopoietic cells. A C-terminal truncation in the cytoplasmic domain of the EPOR renders the receptor hyperresponsive to erythropoietin, but is insufficient to induce hormone-independent growth or tumorigenicity. The activating point mutation retards intracellular transport and turnover of the receptor. These alterations in metabolism and tumorigenicity caused by the EPOR with activating point mutations are similar to those observed in erythropoietin-independent activation of the wild type EPOR by association with gp55, the Friend spleen focus-forming virus glycoprotein.
促红细胞生成素及其他细胞因子的受体构成了一个新的超家族。它们没有酪氨酸激酶或其他酶基序，其信号转导机制尚不清楚。在此，我们描述了促红细胞生成素受体（EPOR）中的两类激活突变。胞外结构域中的单个点突变使其在非致瘤性、依赖白细胞介素-3的造血细胞中表达后能够诱导激素非依赖性细胞生长和肿瘤发生。EPOR胞质结构域的C末端截短使受体对促红细胞生成素反应过度，但不足以诱导激素非依赖性生长或致瘤性。激活点突变会延迟受体的细胞内转运和周转。由具有激活点突变的EPOR引起的这些代谢和致瘤性改变与通过与gp55（弗氏脾脏集落形成病毒糖蛋白）结合而在野生型EPOR的促红细胞生成素非依赖性激活中观察到的改变相似。
