ArticleACS chemical biology2015
Divalent Metal Ions Mg²⁺ and Ca²⁺ Have Distinct Effects on Protein Kinase A Activity and Regulation.
Article in ACS chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 80 citations in OpenAlex.
- Nature Counts to Three: Universal Mg-Pinch Motif Polarizes the Cleaved Bond in NTP-Processing Enzymes.Journal of the American Chemical Society · 2026Article
- Analytical Characterization and Stability Assessment of RNA-Based Vaccines.Pharmaceutics · 2026Review
- Smoothened and ciliary GPCRs regulate ciliary protein kinase A activity involved in Hedgehog signal transduction.PLoS biology · 2026Article
- Pleurotus ostreatus L-asparaginase's use in food safety and biotechnology: from processing assistance to bioactive agent.Microbial cell factories · 2026Article
- Proteomic Snapshots of Structural Cross-Linking Rearrangements in CaJournal of proteome research · 2026Article
- Functional divergence of protein kinase A regulatory subunit Iβ variants: the importance of N3A motifs in PKA regulation.The FEBS journal · 2026Article
- The machinery of healthy vasodilatation: an overview.Pflugers Archiv : European journal of physiology · 2025Review
- Review
- Biochemical and biological evaluation of L-glutaminase from Aspergillus tamarii AUMC 10198 via solid-state fermentation.Microbial cell factories · 2025Article
- A database overview of metal-coordination distances in metalloproteins.Acta crystallographica. Section D, Structural biology · 2024Article
- Cannabis use associated with lower mortality among hospitalized Covid-19 patients using the national inpatient sample: an epidemiological study.Journal of cannabis research · 2024Article
- Flexibility of Binding Site is Essential to the CaJournal of the American Chemical Society · 2024Article
- Age-, sex- and proximal-distal-resolved multi-omics identifies regulators of intestinal aging in non-human primates.Nature aging · 2024Article
- Neuronal ER-plasma membrane junctions couple excitation to CaNature communications · 2023Article
- Real-time observation of functional specialization among phosphorylation sites in CFTR.The Journal of general physiology · 2023Article
- NaInternational journal of molecular sciences · 2022Article
- A PKA inhibitor motif within SMOOTHENED controls Hedgehog signal transduction.Nature structural & molecular biology · 2022Article
- Assaying Protein Kinase A Activity Using a FRET-Based Sensor Purified from Mammalian Cells.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Effect of Divalent Metal Ion on the Structure, Stability and Function ofInternational journal of molecular sciences · 2021Article
- Characterization of a Novel L-Asparaginase fromFoods (Basel, Switzerland) · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
cAMP-dependent protein kinase (PKA) is regulated primarily in response to physiological signals while nucleotides and metals may provide fine-tuning. PKA can use different metal ions for phosphoryl transfer, yet some, like Ca(2+), do not support steady-state catalysis. Fluorescence Polarization (FP) and Surface Plasmon Resonance (SPR) were used to study inhibitor and substrate interactions with PKA. The data illustrate how metals can act differentially as a result of their inherent coordination properties. We found that Ca(2+), in contrast to Mg(2+), does not induce high-affinity binding of PKA to pseudosubstrate inhibitors. However, Ca(2+) works in a single turnover mode to allow for phosphoryl-transfer. Using a novel SPR approach, we were able to directly monitor the interaction of PKA with a substrate in the presence of Mg(2+)ATP. This allows us to depict the entire kinase reaction including complex formation as well as release of the phosphorylated substrate. In contrast to Mg(2+), Ca(2+) apparently slows down the enzymatic reaction. A focus on individual reaction steps revealed that Ca(2+) is not as efficient as Mg(2+) in stabilizing the enzyme:substrate complex. The opposite holds true for product dissociation where Mg(2+) easily releases the phospho-substrate while Ca(2+) traps both reaction products at the active site. This explains the low steady-state activity in the presence of Ca(2+). Furthermore, Ca(2+) is able to modulate kinase activity as well as inhibitor binding even in the presence of Mg(2+). We therefore hypothesize that the physiological metal ions Mg(2+) and Ca(2+) both play a role in kinase activity and regulation. Since PKA is localized close to calcium channels and may render PKA activity susceptible to Ca(2+), our data provide a possible mechanism for novel crosstalk between cAMP and calcium signaling.
Indexed as
Identifiers
What OpenQuestion holds
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.