title: When a G protein-coupled receptor does not couple to a G protein.
abstract: Classically, G protein-coupled receptors (GPCRs) relay signals by directly activating heterotrimeric guanine nucleotide-binding proteins (G proteins). Increasing evidence indicates that GPCRs may also signal through G protein-independent pathways. JAK/STATs, Src-family tyrosine kinases, GRKs/beta-arrestins, and PDZ domain-containing proteins have been suggested to directly relay signals from GPCRs independent of G proteins. In addition, our laboratory recently reported that the beta(2) adrenergic receptor (beta(2)AR) could switch from G protein-coupled to G protein-independent ERK (extracellular signal-regulated kinase) activation in an agonist dosage-dependent manner. This finding provides a novel mechanism for G protein-independent GPCR signaling. This review focuses on recent progress in understanding the mechanisms by which G protein-independent GPCR signaling occurs.
authors.affiliation: Department of Physiology, Cornell University Weill Medical College, 1300 York Ave, New York, NY 10021, USA.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Sun
authors.forename: Deirdre
authors.initials: D
authors.lastname: McGarrigle
authors.forename: Xin-Yun
authors.initials: XY
authors.lastname: Huang
mesh_terms: D019204:GTP-Binding Proteins / Q000378:metabolism*; D008954:Models, Biological; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins