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Sci. Signal., 19 May 2009
Vol. 2, Issue 71, p. ra22
Traditionally, signaling pathways are investigated by measuring the responses of cells to a single factor. Although this approach provides valuable information on the signaling pathways stimulated by that ligand in vitro, the situation in vivo is often much more complex. In the immune system, for example, macrophages are simultaneously exposed to many different cytokines during inflammation. Thus, signaling responses in such contexts cannot reliably be predicted on the basis of single-ligand studies. Hsueh et al. extended a previous analysis of the responses of a macrophage cell line to pairwise combinations of ligands by measuring the cytokines secreted in response to three-, four-, and five-way combinations of ligands and then mathematically analyzing the differences between the expected outcomes (based on lower-order combinations) and the measured outcomes. They found that despite the high number of possible interactions among the stimulated signaling pathways, a modest number of responses were observed. In addition, they also uncovered some unpredicted signaling outcomes, which should help in the future modeling of responses of cells in different contexts.
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).