INTERLEUKIN-3, GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AND INTERLEUKIN-5 TRANSDUCE SIGNALS THROUGH 2 STAT5 HOMOLOGS
INTERLEUKIN-3, GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AND INTERLEUKIN-5 TRANSDUCE SIGNALS THROUGH 2 STAT5 HOMOLOGS
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DOI：
10.1002/j.1460-2075.1995.tb07100.x
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发表时间：
1995-03-15
期刊：
影响因子：
11.4
通讯作者：
MIYAJIMA, A
中科院分区：
文献类型：
--
作者：
MUI, ALF;WAKAO, H;MIYAJIMA, A
白细胞介素3(IL-3)是一种重要的造血调节因子，对其信号转导机制的研究也取得了很大进展。在这篇文章中，我们描述了第一个被IL-3激活的STAT转录因子的分子鉴定。STATs以细胞质中转录不活跃的形式存在，对细胞外信号做出反应，使酪氨酸磷酸化，并转移到细胞核，在那里它们与特定的DNA元件结合。在这些DNA元件中，有几个以IL-3反应的方式与蛋白质结合。对这些带状移位复合体的分析表明，IL-3激活了STAT5的DNA结合能力，STAT5是一种最初被描述为绵羊催乳素反应转录因子的蛋白质。IL-5和粒细胞-巨噬细胞集落刺激因子(GM-CSF)与IL-3共享一个共同的信号受体亚基，也激活STAT5。意想不到的是，分离到了两个氨基酸水平上96%相同的小鼠STAT5同源物，并在转染了IL-3受体和STAT5基因的COS细胞中重建了依赖IL-3的GAS结合。在IL-3依赖的造血细胞中，两种形式的STAT5都被表达和激活，以响应IL-3。
Interleukin-3 (IL-3) is an important regulator of hemopoiesis and considerable effort has been directed towards the study of its mechanism of signal transduction. In this paper, we describe the first molecular identification of a STAT transcription factor that is activated by IL-3. STATs exist in a cytoplasmic, transcriptionally inactive form which, in response to extracellular signals, become tyrosine phosphorylated and translocate to the nucleus where they bind to specific DNA elements. Several of these DNA elements were found which bind proteins in an IL-3-responsive manner. Analysis of these bandshift complexes with available antibodies to the known STATs suggests that IL-3 activates the DNA-binding ability of STAT5, a protein which was originally characterized as a prolactin-responsive transcription factor in sheep. IL-5 and granulocyte-macrophage colony stimulating factor (GM-CSF), which share a common signaling receptor subunit with IL-3, also activate STAT5. Unexpectedly, two murine STAT5 homologs, 96% identical to each other at the amino acid level, were isolated and IL-3-dependent GAS binding could be reconstituted in COS cells transfected with IL-3 receptor and either STAT5 cDNA. In IL-3-dependent hemopoietic cells, both forms of STAT5 are expressed and activated in response to IL-3.