ArticleMolecular pharmacology2015
Adenylyl Cyclase 5 Regulation by Gβγ Involves Isoform-Specific Use of Multiple Interaction Sites.
Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
- Lack of ANKMY2 suppresses kidney cystogenesis in embryonic- and adult-onset polycystic kidney disease.PLoS genetics · 2025Article
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Structure of adenylyl cyclase 5 in complex with Gβγ offers insights into ADCY5-related dyskinesia.Nature structural & molecular biology · 2024Article
- Regulatory sites of CaM-sensitive adenylyl cyclase AC8 revealed by cryo-EM and structural proteomics.EMBO reports · 2024Article
- Potential links between COVID-19 and periodontitis: a bioinformatic analysis based on GEO datasets.BMC oral health · 2022Article
- Distinct Gene Mutations Are Associated With Clinicopathologic Features in Urachal Carcinoma.American journal of clinical pathology · 2022Article
- Physiological roles of mammalian transmembrane adenylyl cyclase isoforms.Physiological reviews · 2022Review
- Critical cysteines in the functional interaction of adenylyl cyclase isoform 6 with Gαs.FASEB bioAdvances · 2022Article
- G protein-coupled receptor-effector macromolecular membrane assemblies (GEMMAs).Pharmacology & therapeutics · 2022Review
- Comprehensive Signaling Profiles Reveal Unsuspected Functional Selectivity of δ-Opioid Receptor Agonists and Allow the Identification of Ligands with the Greatest Potential for Inducing Cyclase Superactivation.ACS pharmacology & translational science · 2021Article
- Combinatorial phosphorylation modulates the structure and function of the G protein γ subunit in yeast.Science signaling · 2021Article
- Subtype-dependent regulation of Gβγ signalling.Cellular signalling · 2021Review
- Multi-functionality of proteins involved in GPCR and G protein signaling: making sense of structure-function continuum with intrinsic disorder-based proteoforms.Cellular and molecular life sciences : CMLS · 2019Review
- G-protein βγ subunits as multi-functional scaffolds and transducers in G-protein-coupled receptor signaling.Cellular and molecular life sciences : CMLS · 2019Review
- Regulation of adenylyl cyclase 5 in striatal neurons confers the ability to detect coincident neuromodulatory signals.PLoS computational biology · 2019Article
- Insights into the Regulatory Properties of Human Adenylyl Cyclase Type 9.Molecular pharmacology · 2019Article
- Pharmacological modulation of the COPharmacology & therapeutics · 2018Review
- Function of Adenylyl Cyclase in Heart: the AKAP Connection.Journal of cardiovascular development and disease · 2018Review
- Loss of type 9 adenylyl cyclase triggers reduced phosphorylation of Hsp20 and diastolic dysfunction.Scientific reports · 2017Article
- International Union of Basic and Clinical Pharmacology. CI. Structures and Small Molecule Modulators of Mammalian Adenylyl Cyclases.Pharmacological reviews · 2017Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Adenylyl cyclase (AC) converts ATP into cyclic AMP (cAMP), an important second messenger in cell signaling. Heterotrimeric G proteins and other regulators are important for control of AC activity. Depending on the AC isoform, Gβγ subunits can either conditionally stimulate or inhibit cAMP synthesis. We previously showed that the Gαs-βγ heterotrimer binds to the N terminus (NT) of type 5 AC (AC5). We now show that Gβγ binds to the NT of a wide variety of AC isoforms. We hypothesized that Gβγ/AC5 interactions involving inactive heterotrimer and Gβγ stimulation of AC5 were separable events. Mutations of the Gβγ "hotspot" show that this site is necessary for AC5 stimulation but not for interactions with the first 198 aa of AC5NT, which is a G protein scaffolding site. This contrasts with AC6, where the Gβγ hotspot is required for both interactions with AC6NT and for stimulation of AC6. Additionally, the SIGK hotspot peptide disrupts Gβγ regulation of AC isoforms 1, 2, and 6, but not AC5. Gβγ also binds the C1/C2 catalytic domains of AC5 and AC6. Finally, cellular interactions with full-length AC5 depend on multiple sites on Gβγ. This suggests an isoform-specific mechanism in which bound Gβγ at the AC5NT is ideally situated for spatiotemporal control of AC5. We propose Gβγ regulation of AC involves multiple binding events, and the role of the AC NT for mechanisms of regulation by heterotrimeric G protein subunits is isoform-specific.
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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.