C/EBPα and G-CSF receptor signals cooperate to induce the myeloperoxidase and neutrophil elastase genes
C/EBPα and G-CSF receptor signals cooperate to induce the myeloperoxidase and neutrophil elastase genes
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DOI：
10.1038/sj.leu.2402094
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发表时间：
2001-05-01
期刊：
影响因子：
11.4
通讯作者：
Friedman, AD
中科院分区：
文献类型：
--
作者：
Wang, W;Wang, X;Friedman, AD
为了评估G-CSF信号和C/EBP α之间的合作，我们表征了表达C/EBP α WT-ER和G-CSF受体（GCSFR）的Ba/F3 pro-B细胞系。在这些细胞系中，GCSFR信号可以独立于其对C/EBP α水平的影响进行评估。单独的G-CSF不诱导MPG、NE、LF或PU.1 RNA，单独的C/EBP α WT-ER刺激低水平MPO和高水平PU.1表达。同时激活GCSFR和C/EBP α WT-ER，24 h时MPO和NE的表达明显增加，48 h时检测到LF mRNA的表达。G-CSF不增加内源性GCSFR、内源性C/EBP α或外源性C/EBP α WT-ER水平，C/EBP α WT-ER不诱导内源性或外源性GCSFR。几种GCSFR突变体也与C/EBP α WT-ER共表达。所有四种胞质酪氨酸的突变阻止NE诱导，但增强MPO诱导。Y 704突变是MPO诱导增加所必需的。与该发现一致，去除IL-3而不添加G-CSF能够通过C/EBP α WT-ER诱导MPG，但不能诱导NE。GCSFR信号或来自其他受体的相关信号可能与C/EBP α合作指导正常骨髓干细胞的分化。
'To assess cooperation between G-CSF signals and C/EBP alpha, we characterized Ba/F3 pro-B cell lines expressing C/EBP alpha WT-ER and the G-CSF receptor (GCSFR). In these lines, GCSFR signals can be evaluated independent of their effect on C/EBP alpha levels. G-CSF alone did not induce the MPG, NE, LF, or PU.1 RNAs, and C/EBP alpha WT-ER alone stimulated low-level MPO and high-level PU.1 expression. Simultaneous activation of the GCSFR and C/EBP alpha WT-ER markedly increased MPO and NE induction at 24 h, and LF mRNA was detected at 48 h. G-CSF did not increase endogenous GCSFR, endogenous C/EBP alpha or exogenous C/EBP alpha WT-ER levels, and C/EBP alpha WT-ER did not induce endogenous or exogenous GCSFR. Several GCSFR mutants were also co-expressed with C/EBP alpha WT-ER. Mutation of all four cytoplasmic tyrosines prevented NE induction but enhanced MPO induction. Mutation of Y704 was required for increased MPO induction. Consistent with this finding, removing IL-3 without G-CSF addition enabled MPG, but not NE, induction by C/EBP alpha WT-ER. GCSFR signals or related signals from other receptors may cooperate with C/EBP alpha to direct differentiation of normal myeloid stem cells.