The mitogen-activated protein kinase (MAPK) cascades are ubiquitous in eukaryotic signal transduction, and these pathways are conserved in cells from yeast to mammals. Metabolic engineering of mammalian cells requires the redesign of the steady-sate and the dynamic responses of signal transduction pathways. Therefore, understanding the design principles of these pathways is a key to success of metabolic engineering for cell culture development and drug target discovery.