zumsande2010bifurcations
Bifurcations and chaos in the MAPK signaling cascade
Martin Zumsande and Thilo Gross
Journal of Theoretical Biology 265, 481-491, 2010
The mitogen-activated protein kinase (MAPK) cascade is an important signaling cascade in eukaryotes. We use the approach of generalized modeling to analyze the dynamics of the MAPK cascade and identify key mechanisms of instability. Furthermore, we report sustained multi-mode oscillations and potentially chaotic behavior caused by a sequestration-based feedback mechanism. Finally, we investigate the interplay between sequestration and external feedback loops. Our analysis thereby confirms, extends and generalizes previous results obtained by conventional modeling and points out the diversity of dynamics that sequestration can bring about.
Figure 1: Schematic overview of the MAPK cascade. The solid arrows correspond to biochemical reactions while the dashed arrows denote the binding of an enzyme in the formation of an substrateenzyme complex. The dotted kinase $$K^1_R$$ (1-layer model) is replaced by $$S^0_1$$ in the larger models. The three different subsystems that we analyzed separately are indicated by boxes. The gray dotted lines represent two types of feedback, which are only included in the model in Sec. 3.7.