Robustness Analysis of the PI3K/AKT Cell Signaling Module

Cell responses are actuated by tightly controlled signal transduction pathways. Due to the complex nature of molecular processes inside the cell, mathematical models recently have been used as a powerful tool to analyze the dynamic properties of cell signaling pathways. Although the concept of an integrated signaling network replete with inter-pathway crosstalk and feedback regulation is broadly appreciated, kinetic data of the type needed to characterize such interactions in conjunction with mathematical models are lacking. In recent years a number of additional criteria such as robustness property have been proposed to validate the proposed mathematical models that should maintain certain important properties of biological systems. In this work we analyze the robustness property of the PI3K/Akt module using the method of perturbation to model rate constants. Simulation results suggested that the perturbation to the activation of Akt and PI3K kinases has more influence on the signal output of the module than other processes in the system. Index Terms—Cell signaling pathway, PI3K/Akt module, mathematical model, robustness analysis, perturbation.