Mitogen-activated protein kinase (MAP kinase) pathways are activated in response to a variety of stimuli involving receptor tyrosine kinases and G-protein coupled receptors (1). Among the various families of MAP kinases, the extracellular signal-regulated kinases (ERK1 and ERK2) are the best characterized. Their involvement in proliferation-related events is highlighted by the fact that their activation is under the control of a signaling cascade of phosphorylation events downstream from the proto-oncogene Ras. Four proteins have emerged as key players in the quest to pharmacologically intervene in this pathway: Ras, Raf, MEK (MAP kinase kinase), and ERK. The reader is referred elsewhere for comprehensive reviews on the role of MAPK cascades in signal transduction (1–3).