@article{Colland01072004, author = {Colland, Frédéric and Jacq, Xavier and Trouplin, Virginie and Mougin, Christelle and Groizeleau, Caroline and Hamburger, Alexandre and Meil, Alain and Wojcik, Jérôme and Legrain, Pierre and Gauthier, Jean-Michel}, title = {Functional Proteomics Mapping of a Human Signaling Pathway}, volume = {14}, number = {7}, pages = {1324-1332}, year = {2004}, doi = {10.1101/gr.2334104}, abstract ={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 β (TGFβ) 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.}, URL = {http://genome.cshlp.org/content/14/7/1324.abstract}, eprint = {http://genome.cshlp.org/content/14/7/1324.full.pdf+html}, journal = {Genome Research} }