ArticleJournal of cell science2012
A key phosphorylation site in AC8 mediates regulation of Ca(2+)-dependent cAMP dynamics by an AC8-AKAP79-PKA signalling complex.
Article in Journal of cell science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- The identification of adenylyl cyclase modulators as potential receptors for 6-nitrodopamine in human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and their relevance in heart inotropism.Frontiers in pharmacology · 2025Article
- Article
- Fluorescent biosensor imaging meets deterministic mathematical modelling: quantitative investigation of signalling compartmentalization.The Journal of physiology · 2023Review
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Multiple Roles of cAMP in Vertebrate Retina.Cells · 2023Review
- POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK-1 in heart.EMBO reports · 2022Article
- Physiological roles of mammalian transmembrane adenylyl cyclase isoforms.Physiological reviews · 2022Review
- Astrocytic Calcium and cAMP in Neurodegenerative Diseases.Frontiers in cellular neuroscience · 2022Review
- Subcellular Organization of the cAMP Signaling Pathway.Pharmacological reviews · 2021Review
- Article
- STIM2 targets Orai1/STIM1 to the AKAP79 signaling complex and confers coupling of CaProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Nanometric targeting of type 9 adenylyl cyclase in heart.Biochemical Society transactions · 2019Review
- Article
- Regulation of ICells · 2019Article
- G-Protein-Coupled Receptors Are Dynamic Regulators of Digestion and Targets for Digestive Diseases.Gastroenterology · 2019Review
- Inhibition by fluoxetine of LH-stimulated cyclic AMP synthesis in tumor Leydig cells partly involves AMPK activation.PloS one · 2019Article
- Targeting FRET-Based Reporters for cAMP and PKA Activity Using AKAP79.Sensors (Basel, Switzerland) · 2018Article
- International Union of Basic and Clinical Pharmacology. CI. Structures and Small Molecule Modulators of Mammalian Adenylyl Cyclases.Pharmacological reviews · 2017Review
- The β2-adrenoceptor activates a positive cAMP-calcium feedforward loop to drive breast cancer cell invasion.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Adenylyl cyclase (AC) isoforms can participate in multimolecular signalling complexes incorporating A-kinase anchoring proteins (AKAPs). We recently identified a direct interaction between Ca(2+)-sensitive AC8 and plasma membrane-targeted AKAP79/150 (in cultured pancreatic insulin-secreting cells and hippocampal neurons), which attenuated the stimulation of AC8 by Ca(2+) entry (Willoughby et al., 2010). Here, we reveal that AKAP79 recruits cAMP-dependent protein kinase (PKA) to mediate the regulatory effects of AKAP79 on AC8 activity. Modulation by PKA is a novel means of AC8 regulation, which may modulate or apply negative feedback to the stimulation of AC8 by Ca(2+) entry. We show that the actions of PKA are not mediated indirectly via PKA-dependent activation of protein phosphatase 2A (PP2A) B56δ subunits that associate with the N-terminus of AC8. By site-directed mutagenesis we identify Ser-112 as an essential residue for direct PKA phosphorylation of AC8 (Ser-112 lies within the N-terminus of AC8, close to the site of AKAP79 association). During a series of experimentally imposed Ca(2+) oscillations, AKAP79-targeted PKA reduced the on-rate of cAMP production in wild-type but not non-phosphorylatable mutants of AC8, which suggests that the protein-protein interaction may provide a feedback mechanism to dampen the downstream consequences of AC8 activation evoked by bursts of Ca(2+) activity. This fine-tuning of Ca(2+)-dependent cAMP dynamics by targeted PKA could be highly significant for cellular events that depend on the interplay of Ca(2+) and cAMP, such as pulsatile hormone secretion and memory formation.
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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.