ArticleProceedings of the National Academy of Sciences of the United States of America2012
Glucocorticoids regulate arrestin gene expression and redirect the signaling profile of G protein-coupled receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Integrated Investigation of Sex Differences in the Human Nociceptin/Orphanin FQ Receptor System: Postmortem Analyses and In Vivo [Biological psychiatry. Cognitive neuroscience and neuroimaging · 2026Article
- Activation of Calcium/Calmodulin-Dependent Kinase II in the Medial Prefrontal Cortex Mediates Spinal Cord Injury-Related Cognitive and Affective Changes.Brain and behavior · 2025Article
- Downregulation of hepatic sulfotransferase 1E1 expression associated with decreased expression of multidrug resistance-associated protein 2.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Comprehensive characterization of platelet function in dogs with hyperadrenocorticism.Haematologica · 2025Article
- Article
- Myeloid beta-arrestin 2 depletion attenuates metabolic dysfunction-associated steatohepatitis via the metabolic reprogramming of macrophages.Cell metabolism · 2024Article
- Antagonism of β-arrestins in IL-4-driven microglia reactivity via the Samd4/mTOR/OXPHOS axis in Parkinson's disease.Science advances · 2024Article
- Prognostic value of β-Arrestins in combination with glucocorticoid receptor in epithelial ovarian cancer.Frontiers in oncology · 2023Article
- GPCRs in the regulation of the functional activity of multipotent mesenchymal stromal cells.Frontiers in cell and developmental biology · 2022Review
- Molecular mechanisms involved in somatostatin receptor regulation in corticotroph tumors: the role of cytoskeleton and USP8 mutations.Endocrine oncology (Bristol, England) · 2022Review
- The long winding road to the safer glucocorticoid receptor (GR) targeting therapies.Oncotarget · 2022Review
- Drug resistance in pituitary tumours: from cell membrane to intracellular signalling.Nature reviews. Endocrinology · 2021Review
- Region-specific mechanisms of corticosteroid-mediated inotropy in rat cardiomyocytes.Scientific reports · 2020Article
- β-Arrestin2 is a critical component of the GPCR-eNOS signalosome.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Glucocorticoids preserve the t-tubular system in ventricular cardiomyocytes by upregulation of autophagic flux.Basic research in cardiology · 2019Article
- 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
- β-Arrestin-1 inhibits glucocorticoid receptor turnover and alters glucocorticoid signaling.The Journal of biological chemistry · 2019Article
- Cell specific interaction of pasireotide: review of preclinical studies in somatotroph and corticotroph pituitary cells.Pituitary · 2019Review
- Article
- Critical Role for GFrontiers in psychiatry · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
G protein-coupled receptors (GPCRs) compose the largest family of cell surface receptors and are the most common target of therapeutic drugs. The nonvisual arrestins, β-arrestin-1 and β-arrestin-2, are multifunctional scaffolding proteins that play critical roles in GPCR signaling. On binding of activated GPCRs at the plasma membrane, β-arrestins terminate G protein-dependent responses (desensitization) and stimulate β-arrestin-dependent signaling pathways. Alterations in the cellular complement of β-arrestin-1 and β-arrestin-2 occur in many human diseases, and their genetic ablation in mice has severe consequences. Surprisingly, however, the factors that control β-arrestin gene expression are poorly understood. We demonstrate that glucocorticoids differentially regulate β-arrestin-1 and β-arrestin-2 gene expression in multiple cell types. Glucocorticoids act via the glucocorticoid receptor (GR) to induce the synthesis of β-arrestin-1 and repress the expression of β-arrestin-2. Glucocorticoid-dependent regulation involves the recruitment of ligand-activated glucocorticoid receptors to conserved and functional glucocorticoid response elements in intron-1 of the β-arrestin-1 gene and intron-11 of the β-arrestin-2 gene. In human lung adenocarcinoma cells, the increased expression of β-arrestin-1 after glucocorticoid treatment impairs G protein-dependent activation of inositol phosphate signaling while enhancing β-arrestin-1-dependent stimulation of the MAPK pathway by protease activated receptor 1. These studies demonstrate that glucocorticoids redirect the signaling profile of GPCRs via alterations in β-arrestin gene expression, revealing a paradigm for cross-talk between nuclear and cell surface receptors and a mechanism by which glucocorticoids alter the clinical efficacy of GPCR-based drugs.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.