Abstract:
:Sharing of positive or negative regulators between multiple targets is frequently observed in cellular signaling cascades. For instance, phosphatase sharing between multiple kinases is ubiquitous within the MAPK pathway. Here we investigate how such phosphatase sharing could shape robustness and evolvability of the phosphorylation cascade. Through modeling and evolutionary simulations, we demonstrate that 1) phosphatase sharing dramatically increases robustness of a bistable MAPK response, and 2) phosphatase-sharing cascades evolve faster than nonsharing cascades. This faster evolution is particularly pronounced when evolving from a monostable toward a bistable phenotype, whereas the transition speed of a population from a bistable to monostable response is not affected by phosphatase sharing. This property may enable the phosphatase-sharing design to adapt better in a changing environment. Analysis of the respective mutational landscapes reveal that phosphatase sharing reduces the number of limiting mutations required for transition from monostable to bistable responses, hence facilitating a faster transition to such response types. Taken together, using MAPK cascade as an example, our study offers a general theoretical framework to explore robustness and evolutionary plasticity of signal transduction cascades.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Ghosh B,Sarma U,Sourjik V,Legewie Sdoi
10.1016/j.bpj.2017.10.037subject
Has Abstractpub_date
2018-01-09 00:00:00pages
223-236issue
1eissn
0006-3495issn
1542-0086pii
S0006-3495(17)31164-5journal_volume
114pub_type
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