Genome-wide RNAi analysis of JAK/STAT signaling components in Drosophila
Genome-wide RNAi analysis of JAK/STAT signaling components in Drosophila
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DOI：
10.1101/gad.1320705
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发表时间：
2005-08-15
影响因子：
10.5
通讯作者：
Perrimon, N
中科院分区：
文献类型：
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作者：
Baeg, GH;Zhou, R;Perrimon, N
细胞因子激活的Janus kinase (JAK)/signal transducer and activator of transcription （STAT）通路在多种生物过程的调控中起着重要作用。当失调时，JAK/STAT信号与多种人类疾病有关，如免疫疾病和肿瘤发生。为了深入了解JAK/STAT信号参与这些不同生物反应的机制，我们在培养的果蝇细胞中进行了全基因组RNA干扰（RNAi）筛选。我们鉴定了121个双链RNA （dsRNA）介导的敲低影响STAT92E活性的基因。在29个阳性调节因子中，13个是STAT92E酪氨酸磷酸化所必需的。此外，我们发现RanBP3和RanBP10的果蝇同源物通过控制STAT92E的核质转运而成为JAK/STAT信号的负调控因子。此外，我们确定了果蝇JAK/STAT信号通路的一个关键负调控因子蛋白酪氨酸磷酸酶PTP61F，并表明它是JAK/STAT信号通路的转录靶点，从而揭示了一个新的负反馈回路。我们的研究发现了JAK/STAT信号通路不同步骤所需的许多未表征的基因。
The cytokine-activated Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway plays an important role in the control of a wide variety of biological processes. When misregulated, JAK/STAT signaling is associated with various human diseases, such as immune disorders and tumorigenesis. To gain insights into the mechanisms by which JAK/STAT signaling participates in these diverse biological responses, we carried out a genome-wide RNA interference (RNAi) screen in cultured Drosophila cells. We identified 121 genes whose double-stranded RNA (dsRNA)-mediated knockdowns affected STAT92E activity. Of the 29 positive regulators, 13 are required for the tyrosine phosphorylation of STAT92E. Furthermore, we found that the Drosophila homologs of RanBP3 and RanBP10 are negative regulators of JAK/STAT signaling through their control of nucleocytoplasmic transport of STAT92E. In addition, we identified a key negative regulator of Drosophila JAK/STAT signaling, protein tyrosine phosphatase PTP61F, and showed that it is a transcriptional target of JAK/STAT signaling, thus revealing a novel negative feedback loop. Our study has uncovered many uncharacterized genes required for different steps of the JAK/STAT signaling pathway.