Goldsmith M A, Mikami A, You Y, Liu K D, Thomas L, Pharr P, Longmore G D
Gladstone Institute of Virology and Immunology, School of Medicine, University of California, San Francisco, San Francisco, CA 94141, USA.
Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):7006-11. doi: 10.1073/pnas.95.12.7006.
Erythropoietin (EPO) is required for red blood cell development, but whether EPO-specific signals directly instruct erythroid differentiation is unknown. We used a dominant system in which constitutively active variants of the EPO receptor were introduced into erythroid progenitors in mice. Chimeric receptors were constructed by replacing the cytoplasmic tail of constitutively active variants of the EPO receptor with tails of diverse cytokine receptors. Receptors linked to granulocyte or platelet production supported complete erythroid development in vitro and in vivo, as did the growth hormone receptor, a nonhematopoietic receptor. Therefore, EPOR-specific signals are not required for terminal differentiation of erythrocytes. Furthermore, we found that cellular context can influence cytokine receptor signaling.
促红细胞生成素(EPO)是红细胞发育所必需的,但EPO特异性信号是否直接指导红系分化尚不清楚。我们使用了一种显性系统,将EPO受体的组成型活性变体导入小鼠的红系祖细胞中。通过用不同细胞因子受体的尾巴替换EPO受体组成型活性变体的细胞质尾巴来构建嵌合受体。与粒细胞或血小板生成相关的受体在体外和体内均支持完全的红系发育,生长激素受体(一种非造血受体)也是如此。因此,红细胞的终末分化不需要EPOR特异性信号。此外,我们发现细胞环境可以影响细胞因子受体信号传导。