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首页> 外文期刊>Cytokine >Distinct functions of erythropoietin and stem cell factor are linked to activation of mTOR kinase signaling pathway in human erythroid progenitors
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Distinct functions of erythropoietin and stem cell factor are linked to activation of mTOR kinase signaling pathway in human erythroid progenitors

机译：促红细胞生成素和干细胞因子的独特功能与人类红系祖细胞中mTOR激酶信号通路的激活有关

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摘要

Erythropoietin (EPO) and Stem Cell Factor (SCF) have partially distinct functions in erythroid cell development. The primary functions of EPO are to prevent apoptosis and promote differentiation, with a minor role as a mitogen. On the other hand SCF acts primarily as a mitogenic factor promoting erythroid cell proliferation with a minor role in inhibition of apoptosis. The concerted effects of these two growth factors are responsible for guiding initial commitment, expansion and differentiation of progenitors. The aim of the study was to identify signaling elements pertinent to translational control and elucidate whether both cytokines can contribute to protein translation providing some functional redundancy as seen with respect to apoptosis. The current study focused on non-apoptotic functions of SCF mediated through mTOR/p70S6 leading to protein translation and cell proliferation. We utilized a human primary erythroid progenitors and erythroblasts that are responsive to EPO and SCF to investigate the activation of mTOR/p70S6 kinases and their downstream effectors, the pathway primarily responsible for protein translation. We showed that mTOR, p70S6 kinases and their downstream signaling elements 4EBP1 and S6 ribosomal protein are all activated by SCF but not by EPO in primary erythroid progenitors. We also found that SCF is the sole contributor to activation of the protein translational machinery and activation of mTOR/p70S6 pathway is confined to the proliferative phase of erythroid differentiation program. Altogether these results demonstrate that unlike the survival function which is supported by both EPO and SCF protein translation essential for proliferation is governed by only SCF.
机译：促红细胞生成素（EPO）和干细胞因子（SCF）在类红细胞发育中具有部分不同的功能。 EPO的主要功能是预防细胞凋亡和促进分化，而其作为促分裂原的作用较小。另一方面，SCF主要充当促红细胞生成素的促有丝分裂因子，而在抑制细胞凋亡中的作用很小。这两个生长因子的协同作用负责指导祖细胞的最初承诺，扩展和分化。该研究的目的是鉴定与翻译控制有关的信号传导元件，并阐明两种细胞因子是否都可以促进蛋白质翻译，从而提供一些有关细胞凋亡的功能冗余。当前的研究集中于通过mTOR / p70S6介导的SCF的非凋亡功能，从而导致蛋白质翻译和细胞增殖。我们利用了对EPO和SCF有反应的人类主要的类红细胞祖细胞和成红细胞，研究了mTOR / p70S6激酶及其下游效应子（主要负责蛋白质翻译的途径）的激活。我们显示，mTOR，p70S6激酶及其下游信号元件4EBP1和S6核糖体蛋白在主要的红系祖细胞中均被SCF激活，但未被EPO激活。我们还发现SCF是激活蛋白质翻译机制的唯一因素，而mTOR / p70S6途径的激活仅限于红系分化程序的增殖期。总而言之，这些结果表明，与EPO和SCF共同支持的生存功能不同，仅由SCF控制增殖所需的蛋白质翻译。

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