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Here we perturb the levels of cAMP within specific cells of an epithelial monolayer to probe the time-dynamic behavior of cell-cell communication protocols implemented by the cAMP\/PKA pathway and its coupling to the ERK pathway. The time-dependent ERK responses we observe in the perturbed cells for spatially uniform cAMP perturbations (all cells) can be very different from those due to spatially localized perturbations (a few cells). Through a combination of pharmacological and genetic perturbations, signal analysis, and computational modeling, we infer how intracellular regulation and regulated cell-cell coupling each impact the intracellular ERK response in single cells. 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