Dynamics of ERK regulation in the processive limit

Abstract

We consider a model of extracellular signal-regulated kinase (ERK) regulation by dual-site phosphorylation and dephosphorylation, which exhibits bistability and oscillations, but loses these properties in the limit in which the mechanisms underlying phosphorylation and dephosphorylation become processive. Our results suggest that anywhere along the way to becoming processive, the model remains bistable and oscillatory. More precisely, in simplified versions of the model, precursors to bistability and oscillations (specifically, multistationarity and Hopf bifurcations, respectively) exist at all "processivity levels". Finally, we investigate whether bistability and oscillations can exist together.