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Cross-talk and decision making in MAP kinase pathways.

Megan N McClean¹, Areez Mody, James R Broach

¹FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts 02138, USA.

Nature Genetics

|January 30, 2007

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Cells achieve specific responses to environmental signals, even with shared proteins, through pathway bistability and mutual inhibition. This system-level mechanism ensures accurate cellular decision-making.

Area of Science:

Cellular Biology
Systems Biology
Biophysics

Background:

Cells must exhibit specific responses to diverse environmental stimuli for survival.
Signal transduction pathways often share homologous proteins, leading to potential cross-talk.
Understanding how pathways achieve specificity despite shared components is crucial.

Purpose of the Study:

To model and elucidate system-level mechanisms for achieving signal transduction specificity.
To investigate how pathways respond to simultaneous and temporally ordered inputs.
To apply these findings to specific signaling pathways in yeast.

Main Methods:

Computational modeling of signal transduction pathways.
Analysis of bistability in biological systems.

Related Experiment Videos

Application of models to yeast hyperosmolar and pheromone pathways.

Main Results:

Modeled pathways demonstrate specificity through system-level mechanisms.
Yeast hyperosmolar and pheromone pathways exhibit bistability.
Cells respond to only one stimulus even when exposed to both, indicating filtered cross-talk.

Conclusions:

Mutual inhibition is a key mechanism for filtering spurious cross-talk and achieving pathway specificity.
Bistability allows cells to make specific decisions in the presence of multiple stimuli.
Cell-to-cell variability contributes to heterogeneity in cellular decision-making.