High-throughput mapping of a dynamic signaling network in mammalian cells
High-throughput mapping of a dynamic signaling network in mammalian cells
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DOI：
10.1126/science.1105776
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发表时间：
2005-03-11
期刊：
影响因子：
56.9
通讯作者：
Wrana, JL
中科院分区：
文献类型：
--
作者：
Barrios-Rodiles, M;Brown, KR;Wrana, JL
信号通路通过复杂的细胞外信号动态调节的蛋白质相互作用网络传递信息。我们开发了LUMIER（基于发光的哺乳动物相互作用组图谱），这是一种自动化的高通量技术，用于系统地绘制哺乳动物细胞中的蛋白质-蛋白质相互作用网络，并将其应用于转化生长因子- β (tgfβ)途径。使用自组织图谱和k-means聚类分析确定了tgf β途径与p21活化激酶（PAK）网络、极性复合物和紧密连接的结构成分Occludin的联系。我们发现Occludin调节tgf β I型受体的定位，从而在上皮细胞向间质细胞转化过程中有效地溶解tgf β依赖的紧密连接。
Signaling pathways transmit information through protein interaction networks that are dynamically regulated by complex extracellular cues. We developed LUMIER (for luminescence-based mammalian interactome mapping), an automated high-throughput technology, to map protein-protein interaction networks systematically in mammalian cells and applied it to the transforming growth factor-beta (TGFbeta) pathway. Analysis using self-organizing maps and k-means clustering identified links of the TGFbeta pathway to the p21 activated kinase (PAK) network, to the polarity complex, and to Occludin, a structural component of tight junctions. We show that Occludin regulates TGFbeta type I receptor localization for efficient TGFbeta-dependent dissolution of tight junctions during epithelial-to-mesenchymal transitions.