Crosstalk in transition: the translocation of Akt

Abstract

Akt/PKB is an important crosstalk node at the junction between a number of major signalling pathways in the mammalian cell. As a significant nutrient sensor, Akt plays a central role in many cellular processes, including cell growth, cell survival and glucose metabolism. The dysregulation of Akt signalling is implicated in the development of many diseases, from diabetes to cancer. The translocation of Akt from cytosol to plasma membrane is a crucial step in Akt activation. Akt is initially synthesized on the endoplasmic reticulum, but translocates to the plasma membrane (PM) in response to insulin stimulation, where it may be activated. The Akt is then recycled to the cytoplasm. The activated Akt may propagate signals to downstream substrates both at the PM and in the cytosol, hence understanding the translocation dynamics is an important step in dissecting the signalling system. At the present time, however, knowledge concerning the translocation of either activated and unactivated Akt is scant. Here we present a simple, deterministic, three-compartment ordinary differential equation model of Akt translocation in vitro. This model can reproduce the salient features of Akt translocation in a manner consistent with the experimental data. Furthermore, we demonstrate that this system is equivalent to a damped harmonic oscillator, and analyse the steady state and transient behaviour of the model over the entire parameter space.

Keywords: Akt/PKB; Insulin signaling; ODE model; Signalling.