How MAP kinase modules function as robust, yet adaptable, circuits

Tian, Tianhai and Harding, Angus (2014) How MAP kinase modules function as robust, yet adaptable, circuits. Cell Cycle, 13 15: 2379-2390. doi:10.4161/cc.29349

Author Tian, Tianhai
Harding, Angus
Title How MAP kinase modules function as robust, yet adaptable, circuits
Journal name Cell Cycle   Check publisher's open access policy
ISSN 1551-4005
Publication date 2014-08-01
Year available 2014
Sub-type Article (original research)
DOI 10.4161/cc.29349
Volume 13
Issue 15
Start page 2379
End page 2390
Total pages 12
Place of publication Austin, TX, United States
Publisher Landes Bioscience
Language eng
Abstract Genetic and biochemical studies have revealed that the diversity of cell types and developmental patterns evident within the animal kingdom is generated by a handful of conserved, core modules. Core biological modules must be robust, able to maintain functionality despite perturbations, and yet sufficiently adaptable for random mutations to generate phenotypic variation during evolution. Understanding how robust, adaptable modules have influenced the evolution of eukaryotes will inform both evolutionary and synthetic biology. One such system is the MAP kinase module, which consists of a 3-tiered kinase circuit configuration that has been evolutionarily conserved from yeast to man. MAP kinase signal transduction pathways are used across eukaryotic phyla to drive biological functions that are crucial for life. Here we ask the fundamental question, why do MAPK modules follow a conserved 3-tiered topology rather than some other number? Using computational simulations, we identify a fundamental 2-tiered circuit topology that can be readily reconfigured by feedback loops and scaffolds to generate diverse signal outputs. When this 2-kinase circuit is connected to proximal input kinases, a 3-tiered modular configuration is created that is both robust and adaptable, providing a biological circuit that can regulate multiple phenotypes and maintain functionality in an uncertain world. We propose that the 3-tiered signal transduction module has been conserved through positive selection, because it facilitated the generation of phenotypic variation during eukaryotic evolution.
Keyword MAP kinase
Facilitated variation
Signal transduction
Systems biology
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 1 times in Thomson Reuters Web of Science Article | Citations
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