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Resistance to signal activation governs design features of the MAP kinase signaling module
Author(s) -
Chapman Stephen,
Asthagiri Anand R.
Publication year - 2003
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.10836
Subject(s) - context (archaeology) , function (biology) , kinase , signal transduction , mitogen activated protein kinase , microbiology and biotechnology , phosphatase , biology , metric (unit) , signal (programming language) , computer science , computational biology , biological system , engineering , phosphorylation , paleontology , operations management , programming language
Given its broad influence over numerous cell functions, redesigning the mitogen‐activated protein (MAP) kinase signaling module would offer a powerful means to engineer cell behavior. Early challenges include identifying quantitative module features most relevant to biological function and developing simple design rules to predictably modify these features. This computational study delineates how features such as signal amplification, input potency, and dynamic range of output may be tuned by manipulating chief module components. Importantly, the model construction identifies a metric of resistance to signal activation that quantitatively predicts module features and design trade‐offs for broad perturbations in kinase and phosphatase expression. Its predictive utility extends to dynamic properties such as signal lifetime, which often dictates MAP kinase effect on cell function. Taken together, we propose that predictably altering MAP kinase signaling by tuning resistance is not only a feasible engineering strategy, but also one exploited by natural systems to allow each MAP kinase to exert pleiotropic effects in a context‐dependent manner. External stimuli not only activate kinases, but also alter phosphatase expression and activity, thereby reconfiguring a single module for quantitatively distinct modes of signaling such as transient vs. sustained dynamics, each with unique effects on cell function. © 2004 Wiley Periodicals, Inc.