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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Arrestins / chemistry
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Arrestins / metabolism
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Cholera Toxin / pharmacology
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Cyclic AMP / physiology
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Cyclic AMP-Dependent Protein Kinases / physiology*
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Endosomes / metabolism*
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Feedback, Physiological
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Fluorescence Resonance Energy Transfer
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HEK293 Cells
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Humans
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Hydrogen-Ion Concentration
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Phosphorylation
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Protein Binding
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Receptor, Parathyroid Hormone, Type 1 / metabolism
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Receptor, Parathyroid Hormone, Type 1 / physiology
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Receptors, G-Protein-Coupled / physiology*
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Signal Transduction / physiology*
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Vacuolar Proton-Translocating ATPases / physiology*
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beta-Arrestins
Substances
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Arrestins
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Receptor, Parathyroid Hormone, Type 1
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Receptors, G-Protein-Coupled
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beta-Arrestins
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Cholera Toxin
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Vacuolar Proton-Translocating ATPases