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 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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Carcinoma, Hepatocellular, Carrier Proteins, Cell Line, Cell Line, Tumor, Computational Biology, Databases, Protein, Gene Library, Homeodomain Proteins, Humans, Kidney, LIM Domain Proteins, Liver Neoplasms, Membrane Proteins, Placenta, Protein Interaction Mapping, Proteomics, Signal Transduction, Trans-Activators, Transcription Factors, Transforming Growth Factor beta, Two-Hybrid System Techniques
Genome Res.
Date: Jul. 01, 2004
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