1. Academic Validation
  2. High-throughput mapping of a dynamic signaling network in mammalian cells

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

  • Science. 2005 Mar 11;307(5715):1621-5. doi: 10.1126/science.1105776.
Miriam Barrios-Rodiles 1 Kevin R Brown Barish Ozdamar Rohit Bose Zhong Liu Robert S Donovan Fukiko Shinjo Yongmei Liu Joanna Dembowy Ian W Taylor Valbona Luga Natasa Przulj Mark Robinson Harukazu Suzuki Yoshihide Hayashizaki Igor Jurisica Jeffrey L Wrana
Affiliations

Affiliation

  • 1 Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5.
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.

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