ArticleBiochemistry2008
Differential regulated interactions of calcium/calmodulin-dependent protein kinase II with isoforms of voltage-gated calcium channel beta subunits.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Systematic Review of Calcium Channels and Intracellular Calcium Signaling: Relevance to Pesticide Neurotoxicity.International journal of molecular sciences · 2021Pooled it
- CaMKII clusters neuronal LTCCs in biomolecular condensates to gate excitation-transcription coupling.bioRxiv : the preprint server for biology · 2025Article
- Using CRISPR-Cas9/phosphoproteomics to identify substrates of calcium/calmodulin-dependent kinase 2δ.The Journal of biological chemistry · 2023Article
- Excitation-transcription coupling, neuronal gene expression and synaptic plasticity.Nature reviews. Neuroscience · 2023Review
- Review
- CaMKII regulates neuromuscular activity and survival of the human blood fluke Schistosoma mansoni.Scientific reports · 2022Article
- Calcium Channel Splice Variants and Their Effects in Brain and Cardiovascular Function.Advances in experimental medicine and biology · 2021Article
- Protein Kinases: Potential Drug Targets AgainstFrontiers in cellular and infection microbiology · 2021Review
- Neuronal L-Type Calcium Channel Signaling to the Nucleus Requires a Novel CaMKIIα-Shank3 Interaction.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- The Interaction between the Drosophila EAG Potassium Channel and the Protein Kinase CaMKII Involves an Extensive Interface at the Active Site of the Kinase.Journal of molecular biology · 2018Article
- Methyl-β-Cyclodextrin Impairs the Phosphorylation of the β₂ Subunit of L-Type Calcium Channels and Cytosolic Calcium Homeostasis in Mature Cerebellar Granule Neurons.International journal of molecular sciences · 2018Article
- CaHeart rhythm · 2018Review
- A novel mechanism for CaThe Journal of biological chemistry · 2017Article
- Calcium/Calmodulin-Dependent Protein Kinase II Activity Persists During Chronic β-Adrenoceptor Blockade in Experimental and Human Heart Failure.Circulation. Heart failure · 2017Article
- Microdomain-Specific Modulation of L-Type Calcium Channels Leads to Triggered Ventricular Arrhythmia in Heart Failure.Circulation research · 2016Article
- CaMKII inhibition in type II pneumocytes protects from bleomycin-induced pulmonary fibrosis by preventing Ca2+-dependent apoptosis.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- LRRK2 Regulates Voltage-Gated Calcium Channel Function.Frontiers in molecular neuroscience · 2016Article
- The role of auxiliary subunits for the functional diversity of voltage-gated calcium channels.Journal of cellular physiology · 2015Review
- Ca(2+) current facilitation is CaMKII-dependent and has arrhythmogenic consequences.Frontiers in pharmacology · 2014Review
- Differential control of calcium homeostasis and vascular reactivity by Ca2+/calmodulin-dependent kinase II.Hypertension (Dallas, Tex. : 1979) · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylates the beta2a subunit of voltage-gated Ca2+ channels at Thr498 to facilitate cardiac L-type Ca2+ channels. CaMKII colocalizes with beta2a in cardiomyocytes and also binds to a domain in beta2a that contains Thr498 and exhibits an amino acid sequence similarity to the CaMKII autoinhibitory domain and to a CaMKII binding domain in the NMDA receptor NR2B subunit (Grueter, C. E. et al. (2006) Mol. Cell 23, 641). Here, we explore the selectivity of the actions of CaMKII among Ca2+ channel beta subunit isoforms. CaMKII phosphorylates the beta1b, beta2a, beta3, and beta4 isoforms with similar initial rates and final stoichiometries of 6-12 mol of phosphate per mol of protein. However, activated/autophosphorylated CaMKII binds to beta1b and beta2a with a similar apparent affinity but does not bind to beta3 or beta4. Prephosphorylation of beta1b and beta2a by CaMKII substantially reduces the binding of autophosphorylated CaMKII. Residues surrounding Thr498 in beta2a are highly conserved in beta1b but are different in beta3 and beta4. Site-directed mutagenesis of this domain in beta2a showed that Thr498 phosphorylation promotes dissociation of CaMKII-beta2a complexes in vitro and reduces interactions of CaMKII with beta2a in cells. Mutagenesis of Leu493 to Ala substantially reduces CaMKII binding in vitro and in intact cells but does not interfere with beta2a phosphorylation at Thr498. In combination, these data show that phosphorylation dynamically regulates the interactions of specific isoforms of the Ca2+ channel beta subunits with CaMKII.
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