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.

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