Sensitivity of CaM Kinase II to the Frequency of Ca 2+ Oscillations
Abstract
The transduction of many cellular stimuli results in oscillations in the intracellular concentration of calcium ions (Ca2+). Although information is thought to be encoded in the frequency of such oscillations, no frequency decoder has been identified. Rapid superfusion of immobilized Ca2+- and calmodulin-dependent protein kinase II (CaM kinase II) in vitro showed that the enzyme can decode the frequency of Ca2+ spikes into distinct amounts of kinase activity. The frequency response of CaM kinase II was modulated by several factors, including the amplitude and duration of individual spikes as well as the subunit composition and previous state of activation of the kinase. These features should provide specificity in the activation of this multifunctional enzyme by distinct cellular stimuli and may underlie its pivotal role in activity-dependent forms of synaptic plasticity.
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T286 autophosphorylation and CaM trapping produce a frequency dependence for CaMKII activation.
“In essence, T286 autophosphorylation and CaM trapping would produce a frequency dependence for CaMKII activation.”
From Synaptic memory and CaMKII (2023) · cites this paper as [69]
Stimulation of CaMKII by brief spikes of Ca2+/CaM achieves activation dependent on spike frequency even when total exposure to Ca2+/CaM is kept constant.
“Third, stimulation of the kinase by brief spikes of Ca2+/CaM achieves activation that is dependent on spike frequency even when total exposure to Ca2+/CaM is kept constant (69).”
From Synaptic memory and CaMKII (2023) · cites this paper as [69]
The linker length affects CaM affinity and Ca2+ spike frequency sensitivity as well as rates of autophosphorylation.
“The linker length affects CaM affinity and Ca2+ spike frequency sensitivity (69, 158) as well as rates of autophosphorylation (159).”
From Synaptic memory and CaMKII (2023) · cites this paper as [69]
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- Authors
- De Koninck, P., & Schulman, H.
- Affiliations
- Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305–5401, USA.
- Stanford Medicine (US)
- Corresponding author
- Schulman, Howard
- ORCID
- Schulman, Howard
- Venue
- Science
- Published
- 1998-01-09
- Volume
- 279
- Issue
- 5348
- Pages
- 227-230
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2135011583
- Cited by
- 1,269
- References
- 2
- Citations by year
- 2026: 17 · 2025: 17 · 2024: 15 · 2023: 22 · 2022: 25 · 2021: 21 · 2020: 28 · 2019: 30 · 2018: 33 · 2017: 29 · 2016: 26 · 2015: 40 · 2014: 37 · 2013: 47 · 2012: 56
- FWCI
- 29.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2r01gm040600-10)
- National Institute of General Medical Sciences (GM40600, GM 30179)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- CaM kinase II, calcium oscillations, oscillation frequency, frequency coding, calmodulin, kinase activity, calcium spikes, subunit composition, synaptic plasticity, signal transduction
- MeSH terms
- Animals, Base Sequence, Calcium, Calmodulin, Chlorocebus aethiops, Enzyme Activation, Enzymes, Immobilized, Molecular Sequence Data, Neuronal Plasticity, Phosphorylation, Phosphothreonine, Polyvinyl Chloride, Recombinant Proteins, Signal Transduction, Calcium-Calmodulin-Dependent Protein Kinases, COS Cells, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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