Publication Date:
2005-03-12
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barrios-Rodiles, Miriam -- Brown, Kevin R -- Ozdamar, Barish -- Bose, Rohit -- Liu, Zhong -- Donovan, Robert S -- Shinjo, Fukiko -- Liu, Yongmei -- Dembowy, Joanna -- Taylor, Ian W -- Luga, Valbona -- Przulj, Natasa -- Robinson, Mark -- Suzuki, Harukazu -- Hayashizaki, Yoshihide -- Jurisica, Igor -- Wrana, Jeffrey L -- P50 GM-62413/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2005 Mar 11;307(5715):1621-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15761153" target="_blank"〉PubMed〈/a〉
Keywords:
Activin Receptors, Type I/metabolism
;
Animals
;
Cell Line
;
Cell Polarity
;
DNA-Binding Proteins/metabolism
;
Epithelial Cells/cytology/physiology
;
Humans
;
Immunoprecipitation
;
Luciferases
;
Membrane Proteins/metabolism
;
Mesoderm/cytology
;
Mice
;
Occludin
;
Phosphorylation
;
*Protein Interaction Mapping
;
Protein-Serine-Threonine Kinases/metabolism
;
Receptors, Transforming Growth Factor beta/metabolism
;
Recombinant Fusion Proteins/metabolism
;
*Signal Transduction
;
Smad2 Protein
;
Smad4 Protein
;
Tight Junctions/ultrastructure
;
Trans-Activators/metabolism
;
Transforming Growth Factor beta/*metabolism
;
p21-Activated Kinases
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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