ArticleProceedings of the National Academy of Sciences of the United States of America2016
Gpr161 anchoring of PKA consolidates GPCR and cAMP signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 106 citations in OpenAlex.
- Centrosome-Signaling Pathway Crosstalk: A Core Hub From Cellular Homeostasis to Disease.Cytoskeleton (Hoboken, N.J.) · 2026Review
- Primary cilia and neural computation.Journal of biomedical science · 2026Review
- Smoothened and ciliary GPCRs regulate ciliary protein kinase A activity involved in Hedgehog signal transduction.PLoS biology · 2026Article
- Hedgehog pathway activity downstream of Smoothened is regulated specifically by basal ciliary PKA.Cellular & molecular biology letters · 2026Article
- Conformational Dynamics and Allostery in the cAMP-Protein Kinase A Signalosome.Advances in experimental medicine and biology · 2026Review
- GPR161-GLI3 repressor signaling at cilia directs apical constriction and cell fate during cranial neural tube closure.Development (Cambridge, England) · 2025Article
- N3A motifs in RIβ mediate allosteric crosstalk between cAMP and ATP in PKA activation.Protein science : a publication of the Protein Society · 2025Article
- Identification of novel interacting proteins of FUZ and GPR161.bioRxiv : the preprint server for biology · 2025Article
- Hedgehog pathway, cell cycle, and primary cilium.Cell death discovery · 2025Review
- G Protein-Coupled Receptor Signal Intersection at the Primary Cilium.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Aberrant phase separation of two PKA RIβ neurological disorder mutants leads to mechanistically distinct signaling deficits.Cell reports · 2025Article
- Cannabinoid Receptor 1 Regulates Zebrafish Renal Multiciliated Cell Development via cAMP Signaling.Journal of developmental biology · 2025Article
- Cilia at the crossroad: convergence of regulatory mechanisms to govern cilia dynamics during cell signaling and the cell cycle.Cell & bioscience · 2025Review
- The evolution of AKAPs and emergence of PKA isotype selective anchoring determinants.The Journal of biological chemistry · 2025Article
- Article
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- A mutation in the PRKAR1B gene drives pathological mechanisms of neurodegeneration across species.Brain : a journal of neurology · 2024Article
- Emerging mechanistic understanding of cilia function in cellular signalling.Nature reviews. Molecular cell biology · 2024Review
- Paracrine Signaling by Pancreatic Islet Cilia.Current opinion in endocrine and metabolic research · 2024Article
- Mechanistic complement of autosomal dominant polycystic kidney disease: the role of aquaporins.Journal of molecular medicine (Berlin, Germany) · 2024Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 6 institutions in 5 countries.
Funding
Abstract
Scaffolding proteins organize the information flow from activated G protein-coupled receptors (GPCRs) to intracellular effector cascades both spatially and temporally. By this means, signaling scaffolds, such as A-kinase anchoring proteins (AKAPs), compartmentalize kinase activity and ensure substrate selectivity. Using a phosphoproteomics approach we identified a physical and functional connection between protein kinase A (PKA) and Gpr161 (an orphan GPCR) signaling. We show that Gpr161 functions as a selective high-affinity AKAP for type I PKA regulatory subunits (RI). Using cell-based reporters to map protein-protein interactions, we discovered that RI binds directly and selectively to a hydrophobic protein-protein interaction interface in the cytoplasmic carboxyl-terminal tail of Gpr161. Furthermore, our data demonstrate that a binary complex between Gpr161 and RI promotes the compartmentalization of Gpr161 to the plasma membrane. Moreover, we show that Gpr161, functioning as an AKAP, recruits PKA RI to primary cilia in zebrafish embryos. We also show that Gpr161 is a target of PKA phosphorylation, and that mutation of the PKA phosphorylation site affects ciliary receptor localization. Thus, we propose that Gpr161 is itself an AKAP and that the cAMP-sensing Gpr161:PKA complex acts as cilium-compartmentalized signalosome, a concept that now needs to be considered in the analyzing, interpreting, and pharmaceutical targeting of PKA-associated functions.
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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.