ArticleMolecular endocrinology (Baltimore, Md.)2011
Structural determinants of agonist-selective signaling at the sst(2A) somatostatin receptor.
Article in Molecular endocrinology (Baltimore, Md.), 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.
- Prospect of acromegaly therapy: molecular mechanism of clinical drugs octreotide and paltusotine.Nature communications · 2023Article
- Neuroendocrine tumor theranostics.Cancer science · 2022Review
- GPCR kinase knockout cells reveal the impact of individual GRKs on arrestin binding and GPCR regulation.Nature communications · 2022Article
- Octreotide and Pasireotide Combination Treatment in Somatotroph Tumor Cells: Predominant Role of SSTCancers · 2021Article
- Comparison of Antinociceptive Effect of Octreotide With Morphine in a Rat Model of Acute Inflammatory Pain.Annals of neurosciences · 2021Article
- Biological and Biochemical Basis of the Differential Efficacy of First and Second Generation Somatostatin Receptor Ligands in Neuroendocrine Neoplasms.International journal of molecular sciences · 2019Review
- International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature.Pharmacological reviews · 2018Review
- Article
- Identification of Phosphorylation Sites Regulating sst3 Somatostatin Receptor Trafficking.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Pasireotide: a novel treatment for patients with acromegaly.Drug design, development and therapy · 2016Review
- Fine-tuning somatostatin receptor signalling by agonist-selective phosphorylation and dephosphorylation: IUPHAR Review 5.British journal of pharmacology · 2014Review
- Article
- Regulated Control of Melanin-Concentrating Hormone Receptor 1 through Posttranslational Modifications.Frontiers in endocrinology · 2013Review
- Phosphorylation of threonine 333 regulates trafficking of the human sst5 somatostatin receptor.Molecular endocrinology (Baltimore, Md.) · 2013Article
- Validation of immunohistochemistry for somatostatin receptor subtype 2A in human somatotropinomas: comparison between quantitative real time RT-PCR and immunohistochemistry.Journal of endocrinological investigation · 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
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The clinically used somatostatin (SS-14) analogs octreotide and pasireotide (SOM230) stimulate distinct species-specific patterns of sst(2A) somatostatin receptor phosphorylation and internalization. Like SS-14, octreotide promotes the phosphorylation of at least six carboxyl-terminal serine and threonine residues, namely S341, S343, T353, T354, T356, and T359, which in turn leads to a robust endocytosis of both rat and human sst(2A) receptors. Unlike SS-14, pasireotide fails to induce any substantial phosphorylation or internalization of the rat sst(2A) receptor. Nevertheless, pasireotide is able to stimulate a selective phosphorylation of S341 and S343 of the human sst(2A) receptor followed by a clearly detectable receptor sequestration. Here, we show that transplantation of amino acids 1-180 of the human sst(2A) receptor to the rat sst(2A) receptor facilitates pasireotide-induced internalization. Conversely, construction of a rat-human sst(2A) chimera conferred resistance to pasireotide-induced internalization. We then created a series of site-directed mutants leading to the identification of amino acids 27, 30, 163, and 164 that when exchanged to their human counterparts facilitated pasireotide-driven S341/S343 phosphorylation and internalization of the rat sst(2A) receptor. Exchange of these amino acids to their rat counterparts completely blocked the pasireotide-mediated internalization of the human sst(2A) receptor. Notably, octreotide and SS-14 stimulated a full phosphorylation and internalization of all mutant sst(2A) receptors tested. Together, these findings suggest that pasireotide activates the sst(2A) receptor via a molecular switch that is structurally and functionally distinct from that turned on during octreotide-driven sst(2A) activation.
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