Mitogen-activated protein kinases (MAPKs) are activated by dual phosphorylation on threonine and tyrosine in response to a wide array of extracellular stimuli. In the yeast Saccharomyces cerevisiae, a series of extracellular stimuli. In the yeast Saccharomyces cerevisiae, a series of MAPK signal transduction pathways have been demonstrated to control many cellular functions. By contrast, mammalian MAPKs are more poorly understood. However, recent studies have established important roles for three separate groups of mammalian MAPKs, which are characterized by distinct dual phosphorylation motifs. Together, these protein kinases mediate signal transduction in mammalian tissues and control many aspects of cellular physiology.