title: Dosage-dependent switch from G protein-coupled to G protein-independent signaling by a GPCR.
abstract: G-protein-coupled receptors (GPCRs) mostly signal through heterotrimeric G proteins. Increasing evidence suggests that GPCRs could function in a G-protein-independent manner. Here, we show that at low concentrations of an agonist, beta(2)-adrenergic receptors (beta(2)-ARs) signal through Galpha(s) to activate the mitogen-activated protein kinase pathway in mouse embryonic fibroblast cells. At high agonist concentrations, signals are also transduced through beta(2)-ARs via an additional pathway that is G-protein-independent but tyrosine kinase Src-dependent. This new dosage-dependent switch of signaling modes of GPCRs has significant implications for GPCR intrinsic properties and desensitization.
authors.affiliation: Department of Physiology, Weill Medical College, Cornell University, New York, NY 10021, USA.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Sun
authors.forename: Jianyun
authors.initials: J
authors.lastname: Huang
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.forename: Murat
authors.initials: M
authors.lastname: Bastepe
authors.forename: Harald
authors.initials: H
authors.lastname: Jüppner
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kobilka
authors.forename: J Jillian
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Xin-Yun
authors.initials: XY
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006224:Cricetinae; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D018343:Receptors, Adrenergic, beta-2; D043562:Receptors, G-Protein-Coupled; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D019204:GTP-Binding Proteins; D019205:GTP-Binding Protein alpha Subunits, Gs