title: High-throughput mapping of a dynamic signaling network in mammalian cells.
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.
authors.affiliation: Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5.
authors.forename: Miriam
authors.initials: M
authors.lastname: Barrios-Rodiles
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Brown
authors.forename: Barish
authors.initials: B
authors.lastname: Ozdamar
authors.forename: Rohit
authors.initials: R
authors.lastname: Bose
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liu
authors.forename: Robert S
authors.initials: RS
authors.lastname: Donovan
authors.forename: Fukiko
authors.initials: F
authors.lastname: Shinjo
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.forename: Joanna
authors.initials: J
authors.lastname: Dembowy
authors.forename: Ian W
authors.initials: IW
authors.lastname: Taylor
authors.forename: Valbona
authors.initials: V
authors.lastname: Luga
authors.forename: Natasa
authors.initials: N
authors.lastname: Przulj
authors.forename: Mark
authors.initials: M
authors.lastname: Robinson
authors.forename: Harukazu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Igor
authors.initials: I
authors.lastname: Jurisica
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Wrana
mesh_terms: D030201:Activin Receptors, Type I / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D004268:DNA-Binding Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases; D008565:Membrane Proteins / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D062793:Occludin; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein; D051901:Smad4 Protein; D019108:Tight Junctions / Q000648:ultrastructure; D015534:Trans-Activators / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D054462:p21-Activated Kinases
chemical_list: D004268:DNA-Binding Proteins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C568986:Ocln protein, mouse; D018125:Receptors, Transforming Growth Factor beta; D011993:Recombinant Fusion Proteins; C497782:SMAD2 protein, human; C497796:SMAD4 protein, human; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051901:Smad4 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D008156:Luciferases; C515903:PAK1 protein, human; C515905:Pak1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II