Sharing of Phosphatases Promotes Response Plasticity in Phosphorylation Cascades
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.
Publisher URL: http://www.cell.com/biophysj/fulltext/S0006-3495(17)31164-5
Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.
Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.