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Science 307 (5715): 1621-1625

Copyright © 2005 by the American Association for the Advancement of Science

High-Throughput Mapping of a Dynamic Signaling Network in Mammalian Cells

Miriam Barrios-Rodiles,1 Kevin R. Brown,2 Barish Ozdamar,1,3 Rohit Bose,1,3 Zhong Liu,1 Robert S. Donovan,1 Fukiko Shinjo,1 Yongmei Liu,1 Joanna Dembowy,1,3 Ian W. Taylor,1,3 Valbona Luga,1,3 Natasa Przulj,4 Mark Robinson,5 Harukazu Suzuki,6 Yoshihide Hayashizaki,6 Igor Jurisica,2,4,7 Jeffrey L. Wrana1,3*

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–ß (TGFß) pathway. Analysis using self-organizing maps and k-means clustering identified links of the TGFß 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 TGFß type I receptor localization for efficient TGFß-dependent dissolution of tight junctions during epithelial-to-mesenchymal transitions.

1 Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5.
2 Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, M5G 2M9.
3 Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario, Canada, M5S 1A8.
4 Department of Computer Science, University of Toronto, Toronto, Ontario, Canada, M5S 3H5.
5 Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada, M5G 1L6.
6 Laboratory for Genome Exploration Research Group, RIKEN Genomic Sciences Center (GSC), Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumiku, Yokohama, 230-0045, Japan.
7 Division of Cancer Informatics, Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, Canada, M5G 2M9.

* To whom correspondence should be addressed. E-mail: wrana{at}mshri.on.ca


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