Functional proteomics mapping of a human signaling pathway

Access to the human genome facilitates extensive functional proteomics studies. Here, we present an integrated approach combining large-scale protein interaction mapping, exploration of the interaction network, and cellular functional assays performed on newly identified proteins involved in a human...

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Bibliographic Details
Published in:Genome research 2004-07, Vol.14 (7), p.1324-1332
Main Authors: Colland, Frédéric, Jacq, Xavier, Trouplin, Virginie, Mougin, Christelle, Groizeleau, Caroline, Hamburger, Alexandre, Meil, Alain, Wojcik, Jérôme, Legrain, Pierre, Gauthier, Jean-Michel
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - pathology
Carrier Proteins - physiology
Cell Line
Cell Line, Tumor
Computational Biology - methods
Databases, Protein
Gene Library
Homeodomain Proteins - physiology
Humans
Kidney - chemistry
Kidney - cytology
Kidney - embryology
Kidney - metabolism
Letters
LIM Domain Proteins
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Membrane Proteins - physiology
Placenta - chemistry
Placenta - metabolism
Protein Interaction Mapping - methods
Proteomics - methods
Signal Transduction - physiology
Trans-Activators - physiology
Transcription Factors - physiology
Transforming Growth Factor beta - physiology
Two-Hybrid System Techniques
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Summary:Access to the human genome facilitates extensive functional proteomics studies. Here, we present an integrated approach combining large-scale protein interaction mapping, exploration of the interaction network, and cellular functional assays performed on newly identified proteins involved in a human signaling pathway. As a proof of principle, we studied the Smad signaling system, which is regulated by members of the transforming growth factor beta (TGFbeta) superfamily. We used two-hybrid screening to map Smad signaling protein-protein interactions and to establish a network of 755 interactions, involving 591 proteins, 179 of which were poorly or not annotated. The exploration of such complex interaction databases is improved by the use of PIMRider, a dedicated navigation tool accessible through the Web. The biological meaning of this network is illustrated by the presence of 18 known Smad-associated proteins. Functional assays performed in mammalian cells including siRNA knock-down experiments identified eight novel proteins involved in Smad signaling, thus validating this integrated functional proteomics approach.
ISSN:1088-9051
1054-9803
1549-5469
DOI:10.1101/gr.2334104