GRKs mediate the sustained suppression of isoproterenol-induced cAMP signals. HEK-293 cells were exposed to 1 μM isoproterenol, followed by a 5-min washout, and a rechallenge with isoproterenol at the times indicated. Shown are representative traces of cells exposed to control intracellular solution (A) or cells exposed to intracellular solution containing PKI (B), 59-74E (C), or PKI + 59-74E (D). (E) Ratio of the peak currents elicited by exposure to isoproterenol (second exposure/first exposure).