ArticlePLoS biology2009
Persistent cAMP-signals triggered by internalized G-protein-coupled receptors.
Article in PLoS biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 313 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
313 citing papers in PubMed, 575 citations in OpenAlex.
- Spatial control of parathyroid hormone receptor-1 signaling dictates ligand-specific biological outcomes.Signal transduction and targeted therapy · 2026Article
- Endosomes: An underappreciated player in cell signal transduction.Fundamental research · 2026Review
- Inhibitory probes for spatiotemporal analysis of GαNature chemical biology · 2026Article
- Arrestins as programmable integrators of GPCR signaling: structural microstates, spatiotemporal logic, and therapeutic control.Cell discovery · 2026Review
- Oncogenic Gα signaling requires AP-3-dependent recruitment to the endolysosomal compartment.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- β-arrestin recruitment facilitates a direct association with G proteins.Nature communications · 2026Article
- Loss of caveolar A1 adenosine receptor signalling blunts anti-adrenergic control in heart failure.Cardiovascular research · 2026Article
- Nanoparticle-mediated antagonism of sustained endosomal signaling of the calcitonin receptor-like receptor provides enhanced and persistent relief of oral cancer pain.Biomaterials · 2026Article
- β-Adrenergic Receptors: Not Always Outside-In.Physiology (Bethesda, Md.) · 2026Review
- Conformational biosensors delineate endosomal G protein regulation by GPCRs.Nature communications · 2026Article
- Phosphovariants of the canonical heterotrimeric Gα protein, GPA1, differentially affect G protein activity and Arabidopsis development.bioRxiv : the preprint server for biology · 2026Article
- Intracrine FFA4 signaling controls lipolysis at lipid droplets.Nature chemical biology · 2026Article
- Spatially diffuse cAMP signalling with oppositely biased GLP-1 receptor agonists in β-cells despite differences in receptor localisation.Molecular metabolism · 2026Article
- Mechanisms of Location Bias in G Protein-Coupled Receptors.Handbook of experimental pharmacology · 2026Review
- Structure-Encoded Location Biased Signaling in a Class B GPCR: Focus on the PTH Type 1 Receptor.Handbook of experimental pharmacology · 2026Review
- Intercellular cyclic nucleotide dynamics mediate oocyte meiosis in mammalian preovulatory follicles.Current topics in developmental biology · 2026Review
- Multi-faceted roles of β-arrestins in G protein-coupled receptor endocytosis.Nature communications · 2025Article
- Class A and B GPCRs trigger rapid GαCommunications biology · 2025Article
- Nanomedicines targeting protease-activated receptor 2 in endosomes provide sustained analgesia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
253 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
G-protein-coupled receptors (GPCRs) are generally thought to signal to second messengers like cyclic AMP (cAMP) from the cell surface and to become internalized upon repeated or prolonged stimulation. Once internalized, they are supposed to stop signaling to second messengers but may trigger nonclassical signals such as mitogen-activated protein kinase (MAPK) activation. Here, we show that a GPCR continues to stimulate cAMP production in a sustained manner after internalization. We generated transgenic mice with ubiquitous expression of a fluorescent sensor for cAMP and studied cAMP responses to thyroid-stimulating hormone (TSH) in native, 3-D thyroid follicles isolated from these mice. TSH stimulation caused internalization of the TSH receptors into a pre-Golgi compartment in close association with G-protein alpha(s)-subunits and adenylyl cyclase III. Receptors internalized together with TSH and produced downstream cellular responses that were distinct from those triggered by cell surface receptors. These data suggest that classical paradigms of GPCR signaling may need revision, as they indicate that cAMP signaling by GPCRs may occur both at the cell surface and from intracellular sites, but with different consequences for the cell.
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.