Bifurcations and chaos in the MAPK signaling cascade.
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.
Zumsande
Martin
M
Max Planck Institute for the Physics of Complex Systems, Nöthnitzer Str. 38, 01187 Dresden, Germany. zumsande@mpipks-dresden.mpg.de
Gross
Thilo
T
D004795:Enzyme Stability / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008954:Models, Biological; D017711:Nonlinear Dynamics; D010766:Phosphorylation; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D048490:raf Kinases / Q000378:metabolism
D036341:Intercellular Signaling Peptides and Proteins; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases; D016283:Proto-Oncogene Proteins p21(ras)