ArticleThe Journal of biological chemistry2011
Differential temporal and spatial regulation of somatostatin receptor phosphorylation and dephosphorylation.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Understanding the influence of lipid bilayers and ligand molecules in determining the conformational dynamics of somatostatin receptor 2.Scientific reports · 2021Article
- The PDZ Domain Protein SYNJ2BP Regulates GRK-Dependent Sst2A Phosphorylation and Downstream MAPK Signaling.Endocrinology · 2021Article
- Regulation of Somatostatin Receptor 2 Trafficking by C-Tail Motifs and the Retromer.Endocrinology · 2019Article
- Identification of Phosphorylation Sites Regulating sst3 Somatostatin Receptor Trafficking.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Protein phosphatase modulation of somatostatin receptor signaling in the mouse hippocampus.Neuropharmacology · 2015Article
- Concomitant action of structural elements and receptor phosphorylation determines arrestin-3 interaction with the free fatty acid receptor FFA4.The Journal of biological chemistry · 2014Article
- Fine-tuning somatostatin receptor signalling by agonist-selective phosphorylation and dephosphorylation: IUPHAR Review 5.British journal of pharmacology · 2014Review
- Differential regulation of somatostatin receptor dephosphorylation by β-arrestin1 and β-arrestin2.Naunyn-Schmiedeberg's archives of pharmacology · 2014Article
- Illuminating somatostatin analog action at neuroendocrine tumor receptors.Trends in pharmacological sciences · 2013Review
- Regulated Control of Melanin-Concentrating Hormone Receptor 1 through Posttranslational Modifications.Frontiers in endocrinology · 2013Review
- G-protein coupled receptor resensitization-appreciating the balancing act of receptor function.Current molecular pharmacology · 2012Article
- Phosphorylation of sst2 receptors in neuroendocrine tumors after octreotide treatment of patients.The American journal of pathology · 2012Article
- Desensitization, trafficking, and resensitization of the pituitary thyrotropin-releasing hormone receptor.Frontiers in neuroscience · 2012Article
- A transplantable phosphorylation probe for direct assessment of G protein-coupled receptor activation.PloS one · 2012Article
- Rapid dephosphorylation of G protein-coupled receptors by protein phosphatase 1β is required for termination of β-arrestin-dependent signaling.The Journal of biological chemistry · 2011Article
- Ligand-dependent mechanisms of sst2A receptor trafficking: role of site-specific phosphorylation and receptor activation in the actions of biased somatostatin agonists.Molecular endocrinology (Baltimore, Md.) · 2011Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The G(i)-coupled somatostatin 2A receptor (sst2A) mediates many of the neuromodulatory and neuroendocrine actions of somatostatin (SS) and is targeted by the SS analogs used to treat neuroendocrine tumors. As for other G protein-coupled receptors, agonists stimulate sst2A receptor phosphorylation on multiple residues, and phosphorylation at different sites has distinct effects on receptor internalization and uncoupling. To elucidate the spatial and temporal regulation of sst2A receptor phosphorylation, we examined agonist-stimulated phosphorylation of multiple receptor GPCR kinase sites using phospho-site-specific antibodies. SS increased receptor phosphorylation sequentially, first on Ser-341/343 and then on Thr-353/354, followed by receptor internalization. Reversal of receptor phosphorylation was determined by the duration of prior agonist exposure. In acutely stimulated cells, in which most receptors remained on the cell surface, dephosphorylation occurred only on Thr-353/354. In contrast, both Ser-341/343 and Thr-353/354 were rapidly dephosphorylated when cells were stimulated long enough to allow receptor internalization before agonist removal. Consistent with these observations, dephosphorylation of Thr-353/354 was not affected by either hypertonic sucrose or dynasore, which prevent receptor internalization, whereas dephosphorylation of Ser-341/343 was completely blocked. An okadaic acid- and fostriecin-sensitive phosphatase catalyzed the dephosphorylation of Thr-353/354 both intracellularly and at the cell surface. In contrast, dephosphorylation of Ser-341/343 was insensitive to these inhibitors. Our results show that the phosphorylation and dephosphorylation of neighboring GPCR kinase sites in the sst2A receptor are subject to differential spatial and temporal regulation. Thus, the pattern of receptor phosphorylation is determined by the duration of agonist stimulation and compartment-specific enzymatic activity.
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Registered trials
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