ArticleBiochemistry2012
Distinct mechanisms of calmodulin binding and regulation of adenylyl cyclases 1 and 8.
Article in Biochemistry, 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, 37 citations in OpenAlex.
- Synergistic Interplay of Stimulatory Cofactors in the Activation of Adenylyl Cyclase Isoform 1.The journal of physical chemistry. B · 2025Article
- Store-operated calcium entry-based targets for novel cancer therapeutic development.The Journal of pharmacology and experimental therapeutics · 2025Review
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Fitting and comparison of calcium-calmodulin kinetic schemes to a common data set using non-linear mixed effects modelling.PloS one · 2025Article
- Pyrazolo-Pyrimidinones with Improved Solubility and Selective Inhibition of Adenylyl Cyclase Type 1 Activity for Treatment of Inflammatory Pain.Journal of medicinal chemistry · 2024Article
- Optimization of a Pyrimidinone Series for Selective Inhibition of CaJournal of medicinal chemistry · 2022Article
- A Selective Adenylyl Cyclase 1 Inhibitor Relieves Pain Without Causing Tolerance.Frontiers in pharmacology · 2022Article
- Protein-protein interaction-based high throughput screening for adenylyl cyclase 1 inhibitors: Design, implementation, and discovery of a novel chemotype.Frontiers in pharmacology · 2022Article
- Cross-Talk Between the Adenylyl Cyclase/cAMP Pathway and CaReviews of physiology, biochemistry and pharmacology · 2021Review
- Article
- Computational Modeling Reveals Frequency Modulation of Calcium-cAMP/PKA Pathway in Dendritic Spines.Biophysical journal · 2019Article
- Competitive Tuning Among CaCellular and molecular bioengineering · 2018Article
- Identification of FDA-Approved Small Molecules Capable of Disrupting the Calmodulin-Adenylyl Cyclase 8 Interaction through Direct Binding to Calmodulin.ACS chemical neuroscience · 2018Article
- A molecular dynamics study of adenylyl cyclase: The impact of ATP and G-protein binding.PloS one · 2018Article
- Competitive tuning: Competition's role in setting the frequency-dependence of Ca2+-dependent proteins.PLoS computational biology · 2017Article
- International Union of Basic and Clinical Pharmacology. CI. Structures and Small Molecule Modulators of Mammalian Adenylyl Cyclases.Pharmacological reviews · 2017Review
- Motor Learning Requires Purkinje Cell Synaptic Potentiation through Activation of AMPA-Receptor Subunit GluA3.Neuron · 2017Article
- Modelling intracellular competition for calcium: kinetic and thermodynamic control of different molecular modes of signal decoding.Scientific reports · 2016Article
- Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent.Breast cancer (Dove Medical Press) · 2016Article
- Gα(i/o)-coupled receptor-mediated sensitization of adenylyl cyclase: 40 years later.European journal of pharmacology · 2015Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Calmodulin (CaM), by mediating the stimulation of the activity of two adenylyl cyclases (ACs), plays a key role in integrating the cAMP and Ca(2+) signaling systems. These ACs, AC1 and AC8, by decoding discrete Ca(2+) signals can contribute to fine-tuning intracellular cAMP dynamics, particularly in neurons where they predominate. CaM comprises an α-helical linker separating two globular regions at the N-terminus and the C-terminus that each bind two Ca(2+) ions. These two lobes have differing affinities for Ca(2+), and they can interact with target proteins independently. This study explores previous indications that the two lobes of CaM can regulate AC1 and AC8 differently and thereby yield different responses to cellular transitions in [Ca(2+)](i). We first compared by glutathione S-transferase pull-down assays and offline nanoelectrospray ionization mass spectrometry the interaction of CaM and Ca(2+)-binding deficient mutants of CaM with the internal CaM binding domain (CaMBD) of AC1 and the two terminal CaMBDs of AC8. We then examined the influence of these three CaMBDs on Ca(2+) binding by native and mutated CaM in stopped-flow experiments to quantify their interactions. The three CaMBDs show quite distinct interactions with the two lobes of CaM. These findings establish the critical kinetic differences between the mechanisms of Ca(2+)-CaM activation of AC1 and AC8, which may underpin their different physiological roles.
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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.