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首页> 外文期刊>Molecular and Cellular Biology >Activation of different Stat5 isoforms contributes to cell-type-restricted signaling in response to interferons.
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Activation of different Stat5 isoforms contributes to cell-type-restricted signaling in response to interferons.

机译：Stat5不同亚型的激活有助于响应干扰素的细胞类型限制信号传导。

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Tyrosine phosphorylation and activation of the transcription factor Stat5 occur in response to stimuli like granulocyte-macrophage colony-stimulating factor, interleukin-3, or erythropoietin that stimulate both proliferation and differentiation of hematopoietic cells. It is unclear whether Stat5 is part of a proliferative response or part of the events leading to cellular differentiation. Here we report that agents promoting differentiation but not proliferation of hematopoietic cells, like phorbol ester or both types of interferons (IFNs), activate Stat5 in promonocytic U937 cells. Both IFN types caused tyrosine phosphorylation and DNA binding of predominantly one Stat5 isoform (Stat5a) despite expression of both Stat5a and Stat5b proteins. Monocytic differentiation of U937 cells led to a strong decrease in IFN-gamma-mediated activation of Stat5 but not of Stat1. Transactivation of Stat5-target genes occurred in response to IFN-gamma, which activates both Stat5 and Stat1, but not in response to granulocyte-macrophage colony-stimulating factor, which activates only Stat5. Tyrosine phosphorylation of Stat5 is not generally part of the IFN response. IFN-gamma did not cause Stat5 activation in HeLa cells, despite the expression of both Stat5 isoforms at similar levels. By contrast, IFN-alpha caused tyrosine phosphorylation and DNA binding of exclusively the b isoform of Stat5, and activated Stat5b formed a DNA binding activity previously found in HeLa cells and designated IFN-alpha activation factor 2. Taken together, our results demonstrate that ligand binding of IFN receptors leads to an isoform-specific activation of Stat5 in a restricted number of cell lineages. Moreover, they suggest that Stat5 might be part of the differentiation response of myeloid cells.
机译：酪氨酸磷酸化和转录因子Stat5的激活是对粒细胞，巨噬细胞集落刺激因子，白细胞介素3或促红细胞生成素等刺激物的刺激，刺激造血细胞的增殖和分化。尚不清楚Stat5是增殖反应的一部分还是导致细胞分化的事件的一部分。在这里我们报告说，促进佛波酯或两种干扰素（IFNs）等造血细胞分化但不促进其增殖的药物，会激活单核细胞U937细胞中的Stat5。尽管Stat5a和Stat5b蛋白均表达，但两种IFN类型均引起酪氨酸磷酸化和DNA结合，主要是一种Stat5亚型（Stat5a）。 U937细胞的单核细胞分化导致Stat5而不是IFN-γ介导的Stat5的激活大大降低。 Stat5靶基因的反式激活是对IFN-γ的激活，它激活了Stat5和Stat1，但对粒细胞-巨噬细胞集落刺激因子（仅激活Stat5）没有响应。 Stat5的酪氨酸磷酸化通常不是IFN反应的一部分。尽管两种Stat5亚型的表达水平相似，但IFN-γ并未在HeLa细胞中引起Stat5激活。相比之下，IFN-α引起酪氨酸的磷酸化和Stat5的b亚型的DNA结合，而激活的Stat5b形成了以前在HeLa细胞中发现的DNA结合活性，并命名为IFN-α激活因子2。在有限数量的细胞谱系中，IFN受体的结合导致Stat5的同工型特异性激活。此外，他们认为Stat5可能是骨髓细胞分化反应的一部分。

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