TY - JOUR T1 - Spatial and Temporal Aspects of Signaling by G-Protein–Coupled Receptors JF - Molecular Pharmacology JO - Mol Pharmacol SP - 572 LP - 578 DO - 10.1124/mol.115.100248 VL - 88 IS - 3 AU - Martin J. Lohse AU - Klaus Peter Hofmann Y1 - 2015/09/01 UR - http://molpharm.aspetjournals.org/content/88/3/572.abstract N2 - Signaling by G-protein–coupled receptors is often considered a uniform process, whereby a homogeneously activated proportion of randomly distributed receptors are activated under equilibrium conditions and produce homogeneous, steady-state intracellular signals. While this may be the case in some biologic systems, the example of rhodopsin with its strictly local single-quantum mode of function shows that homogeneity in space and time cannot be a general property of G-protein–coupled systems. Recent work has now revealed many other systems where such simplicity does not prevail. Instead, a plethora of mechanisms allows much more complex patterns of receptor activation and signaling: different mechanisms of protein-protein interaction; temporal changes under nonequilibrium conditions; localized receptor activation; and localized second messenger generation and degradation—all of which shape receptor-generated signals and permit the creation of multiple signal types. Here, we review the evidence for such pleiotropic receptor signaling in space and time. ER -