Functional interaction of erythropoietin and stem cell factor receptors is essential for erythroid colony formation.
Functional interaction of erythropoietin and stem cell factor receptors is essential for erythroid colony formation.
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促红细胞生成素和干细胞因子受体的功能相互作用对于红细胞集落的形成至关重要。
DOI：
10.1073/pnas.94.5.1806
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发表时间：
1997
影响因子：
11.1
通讯作者：
Lodish,HF
中科院分区：
文献类型：
--
作者：
Wu,H;Klingmüller,U;Acurio,A;Hsiao,JG;Lodish,HF
成熟红细胞的产生需要多种生长因子，但我们不知道它们的作用如何协调。在这里，我们表明，来自促红细胞生成素受体（Epo-R）−/−胎肝的红细胞祖细胞，在体外感染表达野生型Epo-R的逆转录病毒，需要添加Epo和干细胞因子（SCF）以形成红细胞集落形成单位（CFU-E）集落。因此，KIT和Epo-R之间的功能性相互作用，类似于我们在培养细胞中报道的，对于CFU-E祖细胞的功能是必不可少的。相反，正常胎肝祖细胞在体外形成CFU-E集落只需要Epo;激活的KIT和Epo-R之间的必要相互作用必须在CFU-E祖细胞阶段之前或之时在体内发生。使用截短的显性负突变体Epo-Rs，我们表明，KIT不激活Epo-R诱导其二聚化，但可能是通过磷酸化酪氨酸残基（S）在其胞质结构域。通过表达仅含有八个胞质酪氨酸之一的突变型Epo-Rs，我们表明酪氨酸残基Y 464或Y 479足以用于Epo依赖性细胞增殖。然而，只有Epo-R F7 Y 479能够支持在Epo-R−/−胎肝细胞中表达时的红系集落形成，表明Y 464不能发送分化信号或不能响应SCF/KIT激活。本工作采用一种新的实验系统来研究生长因子及其受体在正常造血中的作用。
Production of mature erythrocytes requires multiple growth factors, but we do not know how their actions are coordinated. Here we show that erythroid progenitors from erythropoietin receptor (Epo-R)−/−fetal livers, infectedin vitrowith a retrovirus expressing the wild-type Epo-R, require addition of both Epo and stem cell factor (SCF) to form colony-forming unit erythroid (CFU-E) colonies. Thus, a functional interaction between KIT and the Epo-R, similar to what we reported in cultured cells, is essential for the function of CFU-E progenitors. In contrast, CFU-E colony formationin vitroby normal fetal liver progenitors requires only Epo; the essential interaction between activated KIT and the Epo-R must have occurredin vivobefore or at the CFU-E progenitor stage. Using truncated dominant-negative mutant Epo-Rs, we show that KIT does not activate the Epo-R by inducing its dimerization, but presumably does so by phosphorylating tyrosine residue(s) in its cytosolic domain. By expressing mutant Epo-Rs containing only one of eight cytosolic tyrosines, we show that either tyrosine residue Y464 or Y479 suffices for Epo-dependent cell proliferation. However, only Epo-R F7Y479 is capable of supporting erythroid colony formation when expressed in Epo-R−/−fetal liver cells, indicating that Y464 either cannot send a differentiation signal or fails to respond to SCF/KIT activation. This work employs a novel experimental system to study the function of growth factors and their receptors in normal hematopoiesis.
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影响因子：
10.5
作者：
NOCKA, K;MAJUMDER, S;BESMER, P
通讯作者：
BESMER, P
影响因子：
56.9
作者：
DRANOFF, G;CRAWFORD, AD;MULLIGAN, RC
通讯作者：
MULLIGAN, RC
Epo 诱导受体酪氨酸磷酸化后，造血细胞磷酸酶与促红细胞生成素 (Epo) 受体结合：潜在结合位点的识别。
影响因子：
20.3
作者：
Yi,T;Zhang,J;Miura,O;Ihle,JN
通讯作者：
Ihle,JN
DOI：
10.1073/pnas.93.16.8324
发表时间：
1996-08-06
影响因子：
11.1
作者：
Klingmuller, U;Bergelson, S;Lodish, HF
通讯作者：
Lodish, HF
促红细胞生成素受体和相关蛋白 pp130 的体外磷酸化
影响因子：
5.3
作者：
Akihiko Yoshimura;H. F. Lodish
通讯作者：
H. F. Lodish