ArticleMolecular pharmacology2008
Arrestin binds to different phosphorylated regions of the thyrotropin-releasing hormone receptor with distinct functional consequences.
Article in Molecular pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Article
- Ciliary signaling proteins are mislocalized in the brains of Bardet-Biedl syndrome 1-null mice.Frontiers in cell and developmental biology · 2022Article
- Biochemical and physiological insights into TRH receptor-mediated signaling.Frontiers in cell and developmental biology · 2022Review
- Biased signaling by endogenous opioid peptides.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- G Protein-Coupled Receptor Signaling Through β-Arrestin-Dependent Mechanisms.Journal of cardiovascular pharmacology · 2017Review
- Recent developments in biased agonism.Current opinion in cell biology · 2014Review
- Persistent signaling by thyrotropin-releasing hormone receptors correlates with G-protein and receptor levels.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2012Article
- ßarrestin1-biased agonism at human δ-opioid receptor by peptidic and alkaloid ligands.Cellular signalling · 2012Article
- Desensitization, trafficking, and resensitization of the pituitary thyrotropin-releasing hormone receptor.Frontiers in neuroscience · 2012Article
- β-Arrestin-mediated receptor trafficking and signal transduction.Trends in pharmacological sciences · 2011Review
- Thyrotropin receptor stimulates internalization-independent persistent phosphoinositide signaling.Molecular pharmacology · 2011Article
- Persistent cAMP signaling by thyrotropin (TSH) receptors is not dependent on internalization.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2010Article
- Seven transmembrane receptors as shapeshifting proteins: the impact of allosteric modulation and functional selectivity on new drug discovery.Pharmacological reviews · 2010Review
- Importance of regions outside the cytoplasmic tail of G-protein-coupled receptors for phosphorylation and dephosphorylation.The Biochemical journal · 2010Article
- Role of helix 8 of the thyrotropin-releasing hormone receptor in phosphorylation by G protein-coupled receptor kinase.Molecular pharmacology · 2010Article
- Biased agonism.F1000 biology reports · 2009Article
- Subcellular trafficking of the TRH receptor: effect of phosphorylation.Molecular endocrinology (Baltimore, Md.) · 2009Article
- Rich tapestry of G protein-coupled receptor signaling and regulatory mechanisms.Molecular pharmacology · 2008Review
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2 authors at 1 institution in 1 country.
Funding
Abstract
Arrestin binding to agonist-occupied phosphorylated G protein-coupled receptors typically increases the affinity of agonist binding, increases resistance of receptor-bound agonist to removal with high acid/salt buffer, and leads to receptor desensitization and internalization. We tested whether thyrotropin-releasing hormone (TRH) receptors lacking phosphosites in the C-terminal tail could form stable and functional complexes with arrestin. Fibroblasts from mice lacking arrestins 2 and 3 were used to distinguish between arrestin-dependent and -independent effects. Arrestin did not promote internalization or desensitization of a receptor that had key Ser/Thr phosphosites mutated to Ala (4Ala receptor). Nevertheless, arrestin greatly increased acid/salt resistance and the affinity of 4Ala receptor for TRH. Truncation of 4Ala receptor just distal to the key phosphosites (4AlaStop receptor) abolished arrestin-dependent acid/salt resistance but not the effect of arrestin on agonist affinity. Arrestin formed stable complexes with activated wild-type and 4Ala receptors but not with 4AlaStop receptor, as measured by translocation of arrestin-green fluorescent protein to the plasma membrane or chemical cross-linking. An arrestin mutant that does not interact with clathrin and AP2 did not internalize receptor but still promoted high affinity TRH binding, acid/salt resistance, and desensitization. A sterically restricted arrestin mutant did not cause receptor internalization or desensitization but did promote acid/salt resistance and high agonist affinity. The results demonstrate that arrestin binds to proximal or distal phosphosites in the receptor tail. Arrestin binding at either site causes increased agonist affinity and acid/salt resistance, but only the proximal phosphosites evoke the necessary conformational changes in arrestin for receptor desensitization and internalization.
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