Research ArticleNetwork Modeling

Integration of Protein Abundance and Structure Data Reveals Competition in the ErbB Signaling Network

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Science Signaling  17 Dec 2013:
Vol. 6, Issue 306, pp. ra109
DOI: 10.1126/scisignal.2004560

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Competing for the Hub

Signal transduction involves complex networks of protein-protein interactions. Different signals can produce different responses even if they activate the same receptor or family of receptors; the response can be cell type–specific or cell state–specific, depending on the presence and abundance of the downstream proteins and regulators. Kiel et al. modeled the protein interaction network downstream of the ErbB family of receptor tyrosine kinases, taking into account the structure and abundance of proteins and the binding affinities between interacting proteins. With this information, the authors identified motifs where binding partners compete for a common binding site on a “hub” protein that can act as a branch point for multiple signaling outputs. Furthermore, computational and experimental analysis showed that alterations in the abundance of one of two hub-binding partners affected downstream signaling events. Thus, competition among mutually exclusive binding partners contributes to context-dependent differences in signal transduction.

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