Gpr161 anchoring of PKA consolidates GPCR and cAMP signaling
Open accessAbstract
Significance: At the plasma membrane an array of more than 800 G protein-coupled receptors (GPCRs) receive, convert, amplify, and transmit incoming signals. Activated GPCRs team-up with intracellular scaffolding proteins to compartmentalize signal transmission. Scaffolds, such as β-arrestin and A-kinase anchoring proteins (AKAPs), function as a physical nexus between receptors and molecular switches. Typically, these receptor-bound AKAPs recruit protein kinase A (PKA) to assemble dedicated polyvalent signaling complexes that are spatially and temporally confined. Here, we report that the orphan GPCR, Gpr161, is a PKA substrate and also has an AKAP motif embedded in its C-terminal tail. Our results suggest that Gpr161, by directly recruiting type I PKA holoenzymes to the receptor, creates a cAMP-sensing signalosome. Furthermore, we propose that Gpr161 plays a role in recruiting isoform-specific PKA complexes to primary cilia.
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At least three adenylyl cyclases, ADCY3, ADCY5, and ADCY6, localize to cilia.
“at least three — ADCY3, ADCY5, and ADCY6 — are localized to cilia 143–145.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [144]
The Significance and Subcellular Localization of Gpr161 and PKA Subunits sections discuss recruitment of PKA to primary cilia, not localization of adenylyl cyclases. Searches for ADCY3, ADCY5, ADCY6, and ciliary adenylyl cyclases found no passage addressing the claim. (LLM, conf=0.74)
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Cellular signalling by primary cilia in development, organ function and disease
Anvarian, Z., Mykytyn, K., Mukhopadhyay, S., Pedersen, L. B., & Christensen, S. T. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0116-9 · Cited by 845 · see citing works
- Authors
- Bachmann, V. A., Mayrhofer, J. E., Ilouz, R., Tschaikner, P., Raffeiner, P., Röck, R., Courcelles, M., Apelt, F., Lu, T.-W., Baillie, G. S., Thibault, P., Aanstad, P., Stelzl, U., Taylor, S. S., & Stefan, E.
- Affiliations
- Universität Innsbruck (AT)
- University of California San Diego (US)
- Institute for Research in Immunology and Cancer (CA)
- Max Planck Institute for Molecular Genetics (DE)
- University of Glasgow (GB)
- University of Graz (AT)
- Corresponding author
- Stefan, Eduard
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-06-28
- Volume
- 113
- Issue
- 28
- Pages
- 7786-7791
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4948347
- OpenAlex
- W2416337622
- Cited by
- 111
- References
- 54
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 10 · 2023: 10 · 2022: 9 · 2021: 14 · 2020: 18 · 2019: 11 · 2018: 6 · 2017: 7 · 2016: 3
- FWCI
- 4.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Austrian Science Fund (P22608, P27606, SFB-F44)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
- Keywords
- GPR161, orphan G protein-coupled receptor, A-kinase anchoring proteins, cAMP signaling, signalosome, primary cilia, protein-protein interaction, PKA phosphorylation, plasma membrane anchoring, zebrafish embryos
- MeSH terms
- Cyclic AMP, Amino Acid Sequence, Animals, Humans, Phosphorylation, Zebrafish, Amino Acid Motifs, Receptors, G-Protein-Coupled, Luciferases, Renilla, Mice, Cyclic AMP-Dependent Protein Kinase Type I, A Kinase Anchor Proteins, HEK293 Cells
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