The prolactin receptor rescues EpoR-/- erythroid progenitors and replaces EpoR in a synergistic interaction with c-kit
The prolactin receptor rescues EpoR-/- erythroid progenitors and replaces EpoR in a synergistic interaction with c-kit
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DOI：
10.1182/blood.v92.5.1491.417k40_1491_1496
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发表时间：
1998-09-01
期刊：
影响因子：
20.3
通讯作者：
Lodish, HF
中科院分区：
文献类型：
--
作者：
Socolovsky, M;Fallon, AEJ;Lodish, HF
我们最近发现，逆转录病毒转导的催乳素受体（PrlR）在催乳素和促红细胞生成素（Epo）缺乏的情况下，有效地支持野生型突发性形成单位红细胞（BFU-e）和集落形成单位红细胞（CFU-e）祖细胞的分化。为了直接研究野生型红系祖细胞表达的Epo受体（EpoR）是否对其最终分化至关重要，我们用编码PrlR的逆转录病毒构建体或含有PrlR胞外结构域和EpoR胞内结构域的嵌合受体感染EpoR（-/-）祖细胞。通过对催乳素的反应，两种受体在体外支持EpoR（-/-）祖细胞完全分化为红系集落方面同样有效。因此，红细胞分化不需要Epi，R-unique信号；EpoR信号在红细胞分化过程中无指导作用。EpoR和c-kit之间的协同相互作用对于产生正常数量的红细胞至关重要，正如c-kit及其配体干细胞因子突变的小鼠严重贫血所证明的那样。我们发现干细胞因子的加入增强了PrlR支持Epok（-/-）和野生型CFU-e祖细胞分化的能力，这种协同作用在数量上等同于c-kit和CFU-e祖细胞之间的协同作用。EpoR。因此，c-kit和EpoR之间的协同相互作用不需要EpoR独有的信号。(C) 1998年由美国血液病学会出版。
We recently showed that a retrovirally transduced prolactin receptor (PrlR) efficiently supports the differentiation of wild-type burst-forming unit erythroid (BFU-e) and colony-forming unit erythroid (CFU-e) progenitors in response to prolactin and in the absence of erythropoietin (Epo). To examine directly whether the Epo receptor (EpoR) expressed by wild-type erythroid progenitors was essential for their terminal differentiation, we infected EpoR(-/-) progenitors with retroviral constructs encoding either the PrlR or a chimeric receptor containing the extracellular domain of the PrlR and intracellular domain of EpoR. Ih response to prolactin, both receptors were equally efficient in supporting full differentiation of the EpoR(-/-) progenitors into erythroid colonies in vitro. Therefore, there is no requirement for an Epi,R-unique Signal in erythroid differentiation; EpoR signaling has no instructive role in red blood cell differentiation. A synergistic interaction between EpoR and c-kit is essential for the production of normal numbers of red blood cells, as demonstrated by the severe anemia of mice mutant for either c-kit br its ligand, stem cell factor. We show that the addition of stem cell factor potentiates the ability bf the PrlR to support differentiation of both Epok(-/-) and wild-type CFU-e progenitors,This synergism is quantitatively equivalent to that observed between c-kit and. EpoR. Therefore, there is no requirement for an EpoR-unique signal in the synergistic interaction between c-kit and EpoR. (C)o 1998 by The American Society of Hematology.