MAPK signal specificity: the right place at the right time

Although the mechanisms that lead to activation of the Ras, extracellular-signal-regulated kinase mitogen-activated protein kinase (Ras/ERK-MAPK) signaling pathway have been studied intensively, the fundamental principles that determine how activation of ERK signaling can result in distinct biological outcomes have only recently received attention. Factors such as cell-surface receptor density, expression of scaffolding proteins, the surrounding extracellular matrix, and the interplay between kinases and phosphatases modulate the strength and duration of ERK signaling. Furthermore, the spatial distribution and temporal qualities of ERK can markedly alter the qualitative and quantitative features of downstream signaling to immediate early genes (IEG) and the expression of IEG-encoded protein products. As a result, IEG products provide a molecular interpretation of ERK dynamics, enabling the cell to program an appropriate biological response.