Preassembled GPCR signaling complexes mediate distinct cellular responses to ultralow ligand concentrations.

ABSTRACT: G protein-coupled receptors (GPCRs) are the largest class of cell surface signaling proteins, participate in nearly all physiological processes, and are the targets of 30% of marketed drugs. Typically, nanomolar to micromolar concentrations of ligand are used to activate GPCRs in experimental systems. We detected GPCR responses to a wide range of ligand concentrations, from attomolar to millimolar, by measuring GPCR-stimulated production of cyclic adenosine monophosphate (cAMP) with high spatial and temporal resolution. Mathematical modeling showed that femtomolar concentrations of ligand activated, on average, 40% of the cells in a population provided that a cell was activated by one to two binding events. Furthermore, activation of the endogenous β₂-adrenergic receptor (β

SUBMITTER: Civciristov S 

PROVIDER: S-EPMC7416780 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature