Schematic presentation of the feedback mechanism primarily responsible for the regulation of β₂ adrenergic signaling in HEK-293 cells. Ligand binding to β2ARs leads to activation of adenylyl cyclase and cAMP production. cAMP activates PKA, which in turn phosphorylates and activates PDE4. GRK-mediated phosphorylation of the receptor, and subsequent arrestin binding, is also sufficient to trigger a decay in the near-membrane cAMP signal.