High-throughput mapping of a dynamic signaling network in mammalian cells

M Barrios-Rodiles, KR Brown, B Ozdamar, R Bose… - Science, 2005 - science.org
M Barrios-Rodiles, KR Brown, B Ozdamar, R Bose, Z Liu, RS Donovan, F Shinjo, Y Liu…
Science, 2005science.org
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–β (TGFβ) pathway. Analysis using self-
organizing maps and k-means clustering identified links of the TGFβ pathway to the p21 …
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–β (TGFβ) pathway. Analysis using self-organizing maps and k-means clustering identified links of the TGFβ 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 TGFβ type I receptor localization for efficient TGFβ-dependent dissolution of tight junctions during epithelial-to-mesenchymal transitions.
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