Complexity and Modularity of MAPK Signaling Networks

Signaling through mitogen-activated protein kinase (MAPK) cascades is a conserved and fundamental process in all eukaryotes. This chapter reviews recent progress made in the identification of components of MAPK signaling networks using novel large scale experimental methods. It also presents recent landmarks in the computational modeling and simulation of the dynamics of MAPK signaling modules. The in vitro MAPK signaling network reconstructed from predicted phosphorylation events is dense, supporting the hypothesis of a combinatorial control of transcription through selective phosphorylation of sets of transcription factors. Despite the fact that additional co-factors and scaffold proteins may regulate the dynamics of signal transduction in vivo, the complexity of MAPK signaling networks supports a new model that departs significantly from that of the classical definition of a MAPK cascade.