Mathematical modeling for multisite phosphorylation with scaffold binding in cell signaling.

The mating decision in budding yeast is a switch-like or bistability response that allows cells to filter out weak pheromone signals or avoid improper mating when a mate is sufficiently close. However, the molecular mechanisms that control the bistability decision are not yet fully understood. In many cases, scaffold proteins are thought to play a key role during this process. A workable definition of a scaffold is a protein that dynamically binds to two or more consecutively acting components of a signaling cascade, such as protein kinase and that kinase's substrate. Here, we show that bistability mechanism can arise from multisite phosphorylation system with scaffold binding when phosphorylation and dephosphorylation occur at different locations. This scaffold binding in a multisite phosphorylation system can robustly result in multiple steady states. By developing generic mathematical models, we argue that the scaffold protein plays an important role in creating bistability, and by treating parameters symbolically, we also thereby reduce the complexity of calculating steady states from simulating differential equations to finding the roots of polynomials, of which the degree depends on the number of phosphorylation sites N. [ABSTRACT FROM AUTHOR]