Dynamics of ERK regulation in the processive limit

TL;DR

This paper analyzes a model of ERK regulation, showing that bistability and oscillations persist at various processivity levels but are lost in the fully processive limit, with implications for cellular signaling dynamics.

Contribution

It demonstrates that bistability and oscillations in ERK regulation models exist at all processivity levels until the fully processive limit, providing insights into signal regulation mechanisms.

Findings

Bistability and oscillations persist at all processivity levels.

These properties are lost in the fully processive limit.

Multistationarity and Hopf bifurcations occur at intermediate levels.

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.