Cell signaling: A systems model of signaling identifies a molecular basis set for cytokine-induced apoptosis

Kevin A. Janes, John Albeck, Suzanne Gaudet, Peter K. Sorger, Douglas A. Lauffenburger, Michael B. Yaffe

Research output: Contribution to journalArticle

418 Scopus citations

Abstract

Signal transduction pathways control cellular responses to stimuli, but it is unclear how molecular information is processed as a network. We constructed a systems model of 7980 intracellular signaling events that directly links measurements to 1440 response outputs associated with apoptosis. The model accurately predicted multiple time-dependent apoptotic responses induced by a combination of the death-inducing cytokine tumor necrosis factor with the prosurvival factors epidermal growth factor and insulin. By capturing the role of unsuspected autocrine circuits activated by transforming growth factor-α and interleukin-1α, the model revealed new molecular mechanisms connecting signaling to apoptosis. The model derived two groupings of intracellular signals that constitute fundamental dimensions (molecular "basis axes") within the apoptotic signaling network. Projection along these axes captures the entire measured apoptotic network, suggesting that cell survival is determined by signaling through this canonical basis set.

Original languageEnglish (US)
Pages (from-to)1646-1653
Number of pages8
JournalScience
Volume310
Issue number5754
DOIs
StatePublished - Dec 9 2005
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)
  • General

Fingerprint Dive into the research topics of 'Cell signaling: A systems model of signaling identifies a molecular basis set for cytokine-induced apoptosis'. Together they form a unique fingerprint.

  • Cite this

    Janes, K. A., Albeck, J., Gaudet, S., Sorger, P. K., Lauffenburger, D. A., & Yaffe, M. B. (2005). Cell signaling: A systems model of signaling identifies a molecular basis set for cytokine-induced apoptosis. Science, 310(5754), 1646-1653. https://doi.org/10.1126/science.1116598