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Exploring the Design Space of MAP Kinase Cascades
From Q-bio
Caleb Bashor, Noah Helman, Shude Yan and Wendell Lim
- Abstract
- Exploring the Design Space of MAP Kinase Cascades. The connectivity of some signaling pathways is specified by scaffolds – a protein that functions as a molecular breadboard, organizing individual signaling proteins into a single complex. In principle, pathway linkages and response behaviors could be tuned by altering when particular pathway proteins are recruited by the scaffold. Here we explore using the Ste5 scaffold as a platform to systematically reshape signaling dynamics of the yeast mating MAP kinase pathway. We have introduced a novel interaction site onto the Ste5 scaffold in order to artificially recruit positive or negative regulatory components to the complex. Using this simple framework, we can construct a variety of synthetic positive and negative feedback loops and can rationally engineer the same core pathway to show a wide variety of dose-response and dynamic behaviors, including ultrasensitivity, adaptation, and accelerated and delayed response. These results show how scaffold proteins can play a powerful role in both the evolution and engineering of new dynamic signaling behaviors.
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