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High-throughput mapping of a dynamic signaling network in mammalian cells
Author(s): Barrios-Rodiles M, Brown KR, Ozdamar B, Bose R, Liu Z, Donovan RS, Shinjo F, Liu YM, Dembowy J, Taylor IW, Luga V, Przulj N, Robinson M, Suzuki H, Hayashizaki Y, Jurisica I, Wrana JL
Source: SCIENCE    Volume: 307    Issue: 5715    Pages: 1621-1625    Published: MAR 11 2005  
Times Cited: 154     References: 23     
Abstract: 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.
Document Type: Article
Language: English
Reprint Address: Wrana, JL (reprint author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Mol Biol & Canc, 600 Univ Ave, Toronto, ON M5G 1X5 Canada
Addresses:
1. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Mol Biol & Canc, Toronto, ON M5G 1X5 Canada
2. Univ Toronto, Dept Med Biophys, Toronto, ON M5S 2M9 Canada
3. Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON M5S 1A8 Canada
4. Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3H5 Canada
5. Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5G 1L6 Canada
6. RIKEN Genom Sci Ctr, Yokohama Inst, Lab Genome Explorat Res Grp, Yokohama, Kanagawa 2300045 Japan
7. Princess Margaret Hosp, Ontario Canc Inst, Div Canc Informat, Toronto, ON M5G 2M9 Canada
Publisher: AMER ASSOC ADVANCEMENT SCIENCE, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
Subject Category: Multidisciplinary Sciences
IDS Number: 906ED
ISSN: 0036-8075
DOI: 10.1126/science.1105776
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