de.mpg.escidoc.pubman.appbase.FacesBean
English
 
Help Guide Disclaimer Contact us Login
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

A directed protein interaction network for investigating intracellular signal transduction

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons50573

Stelzl,  U.
Molecular Interaction Networks (Ulrich Stelzl), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

Locator
There are no locators available
Fulltext (public)
There are no public fulltexts available
Supplementary Material (public)
There is no public supplementary material available
Citation

Vinayagam, A., Stelzl, U., Foulle, R., Plassmann, S., Zenkner, M., Timm, J., et al. (2011). A directed protein interaction network for investigating intracellular signal transduction. Sci Signal, 4(189), rs8. Retrieved from http://stke.sciencemag.org/cgi/reprint/sigtrans;4/189/rs8.pdf.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-7854-3
Abstract
Cellular signal transduction is a complex process involving protein-protein interactions (PPIs) that transmit information. For example, signals from the plasma membrane may be transduced to transcription factors to regulate gene expression. To obtain a global view of cellular signaling and to predict potential signal modulators, we searched for protein interaction partners of more than 450 signaling-related proteins by means of automated yeast two-hybrid interaction mating. The resulting PPI network connected 1126 proteins through 2626 PPIs. After expansion of this interaction map with publicly available PPI data, we generated a directed network resembling the signal transduction flow between proteins with a naive Bayesian classifier. We exploited information on the shortest PPI paths from membrane receptors to transcription factors to predict input and output relationships between interacting proteins. Integration of directed PPI with time-resolved protein phosphorylation data revealed network structures that dynamically conveyed information from the activated epidermal growth factor and extracellular signal-regulated kinase (EGF/ERK) signaling cascade to directly associated proteins and more distant proteins in the network. From the model network, we predicted 18 previously unknown modulators of EGF/ERK signaling, which we validated in mammalian cell-based assays. This generic experimental and computational approach provides a framework for elucidating causal connections between signaling proteins and facilitates the identification of proteins that modulate the flow of information in signaling networks.