title: Mixed mechanisms of multi-site phosphorylation.
abstract: Multi-site phosphorylation is ubiquitous in cell biology and has been widely studied experimentally and theoretically. The underlying chemical modification mechanisms are typically assumed to be distributive or processive. In this paper, we study the behaviour of mixed mechanisms that can arise either because phosphorylation and dephosphorylation involve different mechanisms or because phosphorylation and/or dephosphorylation can occur through a combination of mechanisms. We examine a hierarchy of models to assess chemical information processing through different mixed mechanisms, using simulations, bifurcation analysis and analytical work. We demonstrate how mixed mechanisms can show important and unintuitive differences from pure distributive and processive mechanisms, in some cases resulting in monostable behaviour with simple dose-response behaviour, while in other cases generating new behaviour-like oscillations. Our results also suggest patterns of information processing that are relevant as the number of modification sites increases. Overall, our work creates a framework to examine information processing arising from complexities of multi-site modification mechanisms and their impact on signal transduction.
authors.affiliation: Department of Chemical Engineering, Centre for Process Systems Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Thapanar
authors.initials: T
authors.lastname: Suwanmajo
authors.affiliation: Department of Chemical Engineering, Centre for Process Systems Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK Institute for Systems and Synthetic Biology, Imperial College London, South Kensington Campus, London SW7 2AZ, UK j.krishnan@imperial.ac.uk.
authors.forename: J
authors.initials: J
authors.lastname: Krishnan
mesh_terms: D001683:Biological Clocks / Q000502:physiology*; D008954:Models, Biological; D010766:Phosphorylation / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
keywords: information processing; mixed mechanisms; multi-site modification; oscillations; sequestration