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Genome Res. 2004 Jul;14(7):1324-32.

Functional proteomics mapping of a human signaling pathway.

Author information

  • 1Hybrigenics SA, 75014 Paris, France. fcolland@hybrigenics.fr

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 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.

Copyright 2004 Cold Spring Harbor Laboratory Press ISSN

PMID:
15231748
[PubMed - indexed for MEDLINE]
PMCID:
PMC442148
Free PMC Article

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