Arrestins and G proteins in cellular signaling: The coin has two sides

Several studies have suggested that arrestin-mediated signaling by GPCRs requires G protein activation; however, in this issue of Science Signaling, Luttrell et al. documented arrestin-dependent activation of ERK1/2 by a number of GPCRs. These studies do not contradict each other, but illustrate the complexity of cellular signaling that cannot and should not be reduced to simplistic models.