Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Career Basics

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 9 December 2005:
Vol. 310. no. 5754, pp. 1646 - 1653
DOI: 10.1126/science.1116598
Prev | Table of Contents | Next

Research Articles

A Systems Model of Signaling Identifies a Molecular Basis Set for Cytokine-Induced Apoptosis

Kevin A. Janes,1,2* John G. Albeck,2,3* Suzanne Gaudet,2,3 Peter K. Sorger,1,2,3 Douglas A. Lauffenburger,1,2,3 Michael B. Yaffe1,2,3{dagger}

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–{alpha} and interleukin-1{alpha}, 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.

1 Biological Engineering Division, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2 Center for Cell Decision Processes, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3 Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: myaffe{at}mit.edu

Read the Full Text

ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)