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Abstract
As one of the largest and most extensively therapeutically targeted class of receptors, G protein–coupled receptors (also known as seven-transmembrane receptors) are clinically important regulators of physiology. Research highlighted in this issue of Science Signaling provides insight into how receptor phosphorylation enables agonists to trigger distinct cellular responses and how mutations associated with disease affect receptor responsiveness to ligands. This research helps reveal how signaling by these receptors is encoded and decoded to produce ligand-specific, cell-specific, and genome-specific responses.