Martin Zumsande  (Max-Planck-Institut für Physik komplexer Systeme (Dresden), Germany)

Bifurcations and Chaos in the MAPK Signaling Cascade

The mitogen-activated protein kinase (MAPK) cascade is an important signaling pathway in eukaryotic cells. It is involved in a large number of cell functions. Many molecular details of the cascade that consists of multiple phosphorylation cycles are known today. However, many aspects of the dynamics are still unknown, most importantly how exactly the different cell functions can be triggered. We apply the method of generalized modelling [Gross, Feudel: PRE 73, 2006] to a model of the MAPK cascade. We describe how external parameters are correlated with stability of the steady states. Furthermore, we report complex oscillations and potentially chaotic behavior caused by a sequestration-based feedback mechanism. We also 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.