Figure 1: Function of activator and amplifier mutations in the MAPK signaling pathway.

Schema showing the effect of “activator” versus “amplifier” mutants in the MAPK pathway. Activator alterations lead to constitutive MAPK signaling through ERK activation that is independent of upstream pathway activity. Activator mutants strongly activate ERK and lead to negative feedback suppression of upstream signaling. Amplifier mutants augment the downstream signal to ERK and commonly co-occur with other activating mutations upstream in the pathway. They lead to modest activation of ERK and consequently cause minimal negative feedback inhibition of upstream signaling.