Deciphering Akt activation: Insights from a mean-field model

Abstract

Being at the right place at the right time is vital for any signalling system component. Akt/PKB is a well-known low-threshold switch in the mammalian insulin signalling pathway. The activation of Akt is essential for the uptake of glucose, however, data concerning this vital system is very sparse, particularly with regards to cellular location and activation state. Here we present a parsimonious mathematical model that captures the current experimental understanding of Akt dynamics. The system operates on two distinct timescales (signalling and physical transport), with the transportation of Akt constituting the rate-limiting step in most circumstances. The model outputs are consistent with observations of the steady state behaviour of the system and display the transient overshoot behaviour which is a necessary characteristic of the activation of Akt.