ArticleNature chemical biology2014
Spatial encoding of cyclic AMP signaling specificity by GPCR endocytosis.
Article in Nature chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers.
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Who cites it
184 citing papers in PubMed, 294 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
- Biased signaling of β2-adrenergic receptor in physiological and pathological states.Cellular & molecular biology letters · 2026Review
- GPCR-selective effects of endocytosis on cellular signaling through the cAMP/PKA cascade.The Journal of biological chemistry · 2026Article
- G protein GαThe Journal of biological chemistry · 2026Article
- Location-biased β-arrestin conformations direct GPCR signaling.Science signaling · 2026Article
- Differential conservation analysis identifies residues defining constitutive internalization in beta-adrenergic receptors.iScience · 2026Article
- β-Adrenergic Receptors: Not Always Outside-In.Physiology (Bethesda, Md.) · 2026Review
- Conformational biosensors delineate endosomal G protein regulation by GPCRs.Nature communications · 2026Article
- Signaling architecture of the glucagon-like peptide-1 receptor.The Journal of clinical investigation · 2026Review
- Mechanisms of Location Bias in G Protein-Coupled Receptors.Handbook of experimental pharmacology · 2026Review
- Elucidating biased signaling in class A GPCRs.Trends in pharmacological sciences · 2025Review
- Class A and B GPCRs trigger rapid GαCommunications biology · 2025Article
- Two Decades of Optogenetic Tools: A Retrospective and a Look Ahead.Advanced genetics (Hoboken, N.J.) · 2025Review
- Signaling by intracellular βCell reports · 2025Article
- Chemical biology approaches to resolve the subcellular GPCR signaling landscape.Nature chemical biology · 2025Review
- Probing spatiotemporally organized GPCR signaling using genetically encoded molecular tools.Experimental & molecular medicine · 2025Review
124 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
2 authors at 1 institution in 1 country.
Funding
Abstract
G protein-coupled receptors (GPCRs) are well known to signal via cyclic AMP (cAMP) production at the plasma membrane, but it is now clear that various GPCRs also signal after internalization. Apart from its temporal impact through prolonging the cellular response, we wondered whether the endosome-initiated signal encodes any discrete spatial information. Using the β2-adrenoceptor (β2-AR) as a model, we show that endocytosis is required for the full repertoire of downstream cAMP-dependent transcriptional control. Next, we describe an orthogonal optogenetic approach to definitively establish that the location of cAMP production is indeed the critical variable determining the transcriptional response. Finally, our results suggest that this spatial encoding scheme helps cells functionally discriminate chemically distinct β2-AR ligands according to differences in their ability to promote receptor endocytosis. These findings reveal a discrete principle for achieving cellular signaling specificity based on endosome-mediated spatial encoding of intracellular second messenger production and 'location-aware' downstream transcriptional control.
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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.