Cell Signaling

Cell Signaling Goes Live

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Science  25 Mar 2011:
Vol. 331, Issue 6024, pp. 1495
DOI: 10.1126/science.331.6024.1495-c

Elucidation of cellular signaling pathways holds the promise of revealing new therapeutic targets. Such an approach, however, requires a deeper understanding of how signaling pathways interact in regulatory networks and within their physiological niche in vivo. Lau et al. studied effects of the cytokine TNF-α, which contributes to chronic inflammation in diseases such inflammatory bowel disease. TNF-α administration to mice caused apoptosis of epithelial cells in the duodenum, whereas further along the small intestine in the ileum, TNF-α induced proliferation. By characterizing the phosphorylation signals from proteins known to act as critical nodes in cell signaling pathways, the authors constructed mathematical models of the variation in responses to TNF-α. These models predicted that the protein kinase ERK may regulate the distinct regional responses. Pharmacological inhibition of ERK signaling confirmed the predictions and showed that modulation of ERK signaling affected the signaling network beyond the ERK pathway itself. The results show an effective strategy to characterize complex in vivo responses through modeling and then test predictions experimentally, a method that may enhance the development of new therapeutic strategies.

Sci. Signal. 4, ra16 (2011).

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