Letter abstract
Nature Genetics 39, 409 - 414 (2007)
Published online: 28 January 2007 | Corrected online: 14 March 2007 | doi:10.1038/ng1957
There is a Corrigendum (April 2007) associated with this Letter.
Cross-talk and decision making in MAP kinase pathways
Megan N McClean1,2, Areez Mody1, James R Broach3 & Sharad Ramanathan1,4
Cells must respond specifically to different environmental stimuli in order to survive. The signal transduction pathways involved in sensing these stimuli often share the same or homologous proteins. Despite potential cross-wiring, cells show specificity of response. We show, through modeling, that the physiological response of such pathways exposed to simultaneous and temporally ordered inputs can demonstrate system-level mechanisms by which pathways achieve specificity. We apply these results to the hyperosmolar and pheromone mitogen-activated protein (MAP) kinase pathways in the yeast Saccharomyces cerevisiae. These two pathways specifically sense osmolar and pheromone signals1, 2, 3, despite sharing a MAPKKK, Ste11, and having homologous MAPKs (Fus3 and Hog1). We show that in a single cell, the pathways are bistable over a range of inputs, and the cell responds to only one stimulus even when exposed to both. Our results imply that these pathways achieve specificity by filtering out spurious cross-talk through mutual inhibition. The variability between cells allows for heterogeneity of the decisions.
NOTE: In the version of this article initially published,the strain referred to as FUS3D63S on pp.411-412 of the main text and in the figure legend for Figure 5c-f should instead read 5c-f should instead read 5c-f FUS3D317G.The error has been corrected in the PDF version of the article.
- FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
- Division of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA.
- Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
- Bell Laboratories, Lucent Technologies, Murray Hill, New Jersey 07974, USA.
Correspondence to: Sharad Ramanathan1,4 e-mail: sharadr@alcatel-lucent.com
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