Mapping signaling pathway cross-talk in Drosophila cells
Mapping signaling pathway cross-talk in Drosophila cells
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DOI：
10.1073/pnas.1610432113
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发表时间：
2016-08-30
影响因子：
11.1
通讯作者：
Perrimon, Norbert
中科院分区：
文献类型：
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作者：
Ammeux, Noemie;Housden, Benjamin E.;Perrimon, Norbert
在发育和稳态过程中，细胞整合来自邻近细胞或系统的多种信号。反过来，响应细胞可以产生以自分泌、旁分泌或内分泌方式起作用的信号。尽管细胞间通讯中使用的信号和途径的性质得到了很好的表征，但在大多数情况下，我们缺乏描述途径之间空间和时间相互作用的信号传导的综合观点（例如，当特定结果需要两个通路时，信号是顺序处理还是伴随处理）。为了解决主要后生动物信号通路之间的串扰程度，我们的特点是立即转录反应，无论是单一或多个通路刺激同质果蝇细胞系。我们的研究集中在七个核心通路，表皮生长因子受体（EGFR），骨形态发生蛋白（BMP），Jun激酶（JNK），JAK/STAT，Notch，胰岛素和Wnt，揭示了许多配体和受体是信号传导通路的主要靶点，突出了编码通路组分的基因的转录调控是信号传导串扰的主要水平。此外，我们发现配体和受体可以整合多个途径的活动，并相应地调节其转录反应。
During development and homeostasis, cells integratemultiple signals originating either from neighboring cells or systemically. In turn, responding cells can produce signals that act in an autocrine, paracrine, or endocrine manner. Although the nature of the signals and pathways used in cell-cell communication are well characterized, we lack, inmost cases, an integrative view of signaling describing the spatial and temporal interactions between pathways (e.g., whether the signals are processed sequentially or concomitantly when two pathways are required for a specific outcome). To address the extent of cross-talk between the major metazoan signaling pathways, we characterized immediate transcriptional responses to either single-or multiple pathway stimulations in homogeneous Drosophila cell lines. Our study, focusing on seven core pathways, epidermal growth factor receptor (EGFR), bone morphogenetic protein (BMP), Jun kinase (JNK), JAK/STAT, Notch, Insulin, and Wnt, revealed that many ligands and receptors are primary targets of signaling pathways, highlighting that transcriptional regulation of genes encoding pathway components is a major level of signaling cross-talk. In addition, we found that ligands and receptors can integrate multiple pathway activities and adjust their transcriptional responses accordingly.