title: Endosomal GPCR signaling turned off by negative feedback actions of PKA and v-ATPase.
abstract: The PTH receptor is to our knowledge one of the first G protein-coupled receptor (GPCR) found to sustain cAMP signaling after internalization of the ligand-receptor complex in endosomes. This unexpected model is adding a new dimension on how we think about GPCR signaling, but its mechanism is incompletely understood. We report here that endosomal acidification mediated by the PKA action on the v-ATPase provides a negative feedback mechanism by which endosomal receptor signaling is turned off.
authors: Laboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Alexandre
authors: A
authors: Gidon
authors: Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Mohammad M
authors: MM
authors: Al-Bataineh
authors: Laboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Frederic G
authors: FG
authors: Jean-Alphonse
authors: Department of Structural Biology Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Hilary P
authors: HP
authors: Stevenson
authors: Endocrine Unit, Massachusetts General Hospital-Harvard Medical School, Boston, Massachusetts, USA.
authors: Tomoyuki
authors: T
authors: Watanabe
authors: Laboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Claire
authors: C
authors: Louet
authors: Endocrine Unit, Massachusetts General Hospital-Harvard Medical School, Boston, Massachusetts, USA.
authors: Ashok
authors: A
authors: Khatri
authors: Department of Structural Biology Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Guillermo
authors: G
authors: Calero
authors: Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Núria M
authors: NM
authors: Pastor-Soler
authors: Endocrine Unit, Massachusetts General Hospital-Harvard Medical School, Boston, Massachusetts, USA.
authors: Thomas J
authors: TJ
authors: Gardella
authors: Laboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Jean-Pierre
authors: JP
authors: Vilardaga
mesh_terms: D019390:Arrestins / Q000737:chemistry / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism*; D025461:Feedback, Physiological; D031541:Fluorescence Resonance Energy Transfer; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010766:Phosphorylation; D011485:Protein Binding; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D025262:Vacuolar Proton-Translocating ATPases / Q000502:physiology*; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D044168:Receptor, Parathyroid Hormone, Type 1; D043562:Receptors, G-Protein-Coupled; D000071557:beta-Arrestins; D002772:Cholera Toxin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D025262:Vacuolar Proton-Translocating ATPases