Investigating Differential Dynamics of the MAPK Signaling Cascade Using a Multi-Parametric Global Sensitivity Analysis
2009

Investigating MAPK Signaling Dynamics

Sample size: 10000 publication 10 minutes Evidence: high

Author Information

Author(s): Yoon Jeongah Deisboeck, Thomas S.

Primary Institution: Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital

Hypothesis

What are the key components regulating the differential dynamics of the MAPK signaling cascade?

Conclusion

The study identifies that the intermediate module of the MAPK signaling pathway plays a crucial role in determining whether ERK responses are transient or sustained.

Supporting Evidence

  • The study systematically perturbed the entire parameter space of the MAPK signaling cascade.
  • Key components like Ras and Raf were identified as critical for regulating ERK responses.
  • Initial concentrations of proteins significantly influenced the signaling outputs.

Takeaway

This study looks at how different proteins in a cell help decide if a signal lasts a short time or a long time, which is important for understanding how cells grow and behave.

Methodology

The study used a Monte Carlo simulation to perturb parameters in the EGF-induced MAPK signaling pathway and analyzed the resulting ERK activation profiles.

Limitations

The study may not capture all interactive effects between distant parametric factors.

Digital Object Identifier (DOI)

10.1371/journal.pone.0004560

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