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Review

MAPK signaling in equations and embryos

Stanislav Y. Shvartsman, Mathieu Coppey and Alexander M. Berezhkovskii

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The Extracellularly Regulated Kinase/Mitogen Activated Protein Kinase (ERK/MAPK) signaling pathway is a critical regulator of cellular processes in adult and developing tissues. Depending on the cellular context, MAPK cascade can act as a rheostat, a switch, or an oscillator. The highly conserved structure of the cascade does not imply a rigid function, as was suggested by the early mathematical models of MAPK signaling, and can instead produce a wide range of input-output maps. Given a large number of pathway components and modes of regulation, it is essential to establish experimental systems that will allow both manipulating the MAPK cascade and monitoring its dynamics. The terminal patterning system in the Drosophila embryo appears to be ideally suited for this purpose. Our recent experiments characterized dynamics of the MAPK phosphorylation gradient in the terminal system and proposed that it is regulated by a cascade of diffusion-trapping modules. Here we discuss a biophysical model that can describe the observed dynamics and guide future experiments for exploring the relative importance of multiple layers of MAPK cascade regulation.

Authors

Stanislav Y. Shvartsman Corresponding author: stas@princeton.edu

Lewis-Sigler Institute for Integrative Genomics and Department of Chemical Engineering; Princeton University; Princeton, NJ USA

Mathieu Coppey

Lewis-Sigler Institute for Integrative Genomics and Department of Chemical Engineering; Princeton University; Princeton, NJ USA

Alexander M. Berezhkovskii

2Mathematical and Statistical Computing Laboratory, Division of Computational Bioscience, Center for Information Technology; National Institutes of Health; Bethesda, MD USA

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