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Deciphering Signaling Outcomes from a System of Complex Networks

Hsueh, Robert C. and Natarajan, Madhusudan and Fraser, Iain and Pond, Blake and Liu, Jamie and Mumby, Susanne and Han, Heping and Jiang, Lily I. and Simon, Melvin I. and Taussig, Ronald and Sternweis, Paul C. (2009) Deciphering Signaling Outcomes from a System of Complex Networks. Science Signaling, 2 (71). Art. No. ra22 . ISSN 1937-9145. PMCID PMC2711542.

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Cellular signal transduction machinery integrates information from multiple inputs to actuate discrete cellular behaviors. Interaction complexity exists when an input modulates the output behavior that results from other inputs. To address whether this machinery is iteratively complex—that is, whether increasing numbers of inputs produce exponential increases in discrete cellular behaviors—we examined the modulated secretion of six cytokines from macrophages in response to up to five-way combinations of an agonist of Toll-like receptor 4, three cytokines, and conditions that activated the cyclic adenosine monophosphate pathway. Although all of the selected ligands showed synergy in paired combinations, few examples of nonadditive outputs were found in response to higher-order combinations. This suggests that most potential interactions are not realized and that unique cellular responses are limited to discrete subsets of ligands and pathways that enhance specific cellular functions.

Item Type:Article
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URLURL TypeDescription CentralArticle
Additional Information:© 2009 American Association for the Advancement of Science. Submitted 23 September 2008. Accepted 1 May 2009. Final Publication 19 May 2009.
Issue or Number:71
PubMed Central ID:PMC2711542
Record Number:CaltechAUTHORS:20100414-150652667
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Official Citation:R. C. Hsueh, M. Natarajan, I. Fraser, B. Pond, J. Liu, S. Mumby, H. Han, L. I. Jiang, M. I. Simon, R. Taussig, P. C. Sternweis, Deciphering signaling outcomes from a system of complex networks. Sci. Signal. 2, ra22 (2009).
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:17984
Deposited By: Tony Diaz
Deposited On:28 Apr 2010 18:18
Last Modified:03 Oct 2019 01:36

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