Signal transduction in the erythropoietin receptor system.
Signal transduction in the erythropoietin receptor system.
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DOI：
10.1006/excr.1999.4673
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发表时间：
1999-11
影响因子：
3.7
通讯作者：
D. Wojchowski;R. Gregory;Chris P. Miller;Ajay K. Pandit;T. Pircher
中科院分区：
文献类型：
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作者：
D. Wojchowski;R. Gregory;Chris P. Miller;Ajay K. Pandit;T. Pircher
通过促红细胞生成素（Epo）的单跨膜受体传递的事件对于定型红系祖细胞在集落形成单位-红系阶段之后的发育是必不可少的，这显然涉及Epo对程序性细胞死亡（PCD）的抑制。然而，不太好解决的问题，关于确切的性质Epo依赖的抗凋亡机制，在何种程度上Epo也可能促进有丝分裂和/或终末红细胞分化，以及某些Epo受体胞质亚结构域，信号转导因子和下游途径的基本与调节性质。本文就Epo信号转导的以下几个方面进行了综述：（1）Epo受体/Jak 2激活机制;（2）（P）Y位点和SH 2结构域编码效应子在生存、生长和分化反应中的关键性和非关键性;（3）Epo抑制PCD的主要机制;（4）由共表达的和可能直接相互作用的细胞因子受体传递的信号的整合;和（5）关于效应子功能的预测，其由某些原发性和家族性红细胞增多症与突变的人Epo受体形式的关联提供。
Events relayed via the single transmembrane receptor for erythropoietin (Epo) are essential for the development of committed erythroid progenitor cells beyond the colony-forming unit-erythroid stage, and this clearly involves Epo's inhibition of programmed cell death (PCD). Less well resolved, however, are issues regarding the precise nature of Epo-dependent antiapoptotic mechanisms, the extent to which Epo might also promote mitogenesis and/or terminal erythroid differentiation, and the essential vs modulatory nature of certain Epo receptor cytoplasmic subdomains, signal transducing factors, and downstream pathways. Accordingly, this review focuses on the following aspects of Epo signal transduction: (1) Epo receptor/Jak2 activation mechanisms; (2) the critical vs dispensable nature of (P)Y sites and SH2 domain-encoding effectors in survival, growth, and differentiation responses; (3) primary mechanisms by which Epo inhibits PCD; (4) the integration of signals relayed by coexpressed and possibly directly interacting cytokine receptors; and (5) predictions regarding effector function which are provided by the association of certain primary and familial polycythemias with mutated human Epo receptor forms.