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

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.
Mesh Terms:
Activin Receptors, Type I, Animals, Cell Line, Cell Polarity, DNA-Binding Proteins, Epithelial Cells, Humans, Immunoprecipitation, Luciferases, Membrane Proteins, Mesoderm, Mice, Phosphorylation, Protein Interaction Mapping, Protein-Serine-Threonine Kinases, Receptors, Transforming Growth Factor beta, Recombinant Fusion Proteins, Signal Transduction, Smad2 Protein, Smad4 Protein, Tight Junctions, Trans-Activators, Transforming Growth Factor beta, p21-Activated Kinases
Date: Mar. 11, 2005
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