Deciphering signaling outcomes from a system of complex networks

Robert C. Hsueh, Madhusudan Natarajan, Iain Fraser, Blake Pond, Jamie Liu, Susanne Mumby, Heping Han, Lily I. Jiang, Melvin I. Simon, Ronald Taussig, Paul C. Sternweis

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)ra22
JournalScience signaling
Issue number71
StatePublished - May 19 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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