The DOI matches its Crossref record.
Differential Inactivation of Postsynaptic Density‐Associated and Soluble Ca2+/Calmodulin‐Dependent Protein Kinase II by Protein Phosphatases 1 and 2A
Abstract
Autophosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) at Thr286 generates Ca2+-independent activity. As an initial step toward understanding CaMKII inactivation, protein phosphatase classes (PP1, PP2A, PP2B, or PP2C) responsible for dephosphorylation of Thr286 in rat forebrain subcellular fractions were identified using phosphatase inhibitors/activators, by fractionation using ion exchange chromatography and by immunoblotting. PP2A-like enzymes account for >70% of activity toward exogenous soluble Thr286-autophosphorylated CaMKII in crude cytosol, membrane, and cytoskeletal extracts; PP1 and PP2C account for the remaining activity. CaMKII is present in particulate fractions, specifically associated with postsynaptic densities (PSDs); each protein phosphatase is also present in isolated PSDs, but only PP1 is enriched during PSD isolation. When isolated PSDs dephosphorylated exogenous soluble Thr286-autophosphorylated CaMKII, PP2A again made the major contribution. However, CaMKII endogenous to PSDs (32P autophosphorylated in the presence of Ca2+/calmodulin) was predominantly dephosphorylated by PP1. In addition, dephosphorylation of soluble and PSD-associated CaMKII in whole forebrain extracts was catalyzed predominantly by PP2A and PP1, respectively. Thus, soluble and PSD-associated forms of CaMKII appear to be dephosphorylated by distinct enzymes, suggesting that Ca2+-independent activity of CaMKII is differentially regulated by protein phosphatases in…
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PP1 is the likely phosphatase for preventing spread of CaMKII active state, as it is concentrated in the PSD, whereas PP2A is abundant in cytoplasm, and CaMKII in PSD is preferentially dephosphorylated by PP1.
“PP1 is the likely phosphatase for such a role, as it is concentrated in the PSD, whereas PP2A is abundant in the cytoplasm (64, 385, 386) and CaMKII in the PSD is preferentially dephosphorylated by PP1 (385).”
From Synaptic memory and CaMKII (2023) · cites this paper as [385]
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BackgroundIs Persistent Activity of Calcium/Calmodulin-Dependent Kinase Required for the Maintenance of LTP?
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Metadata
- Authors
- Strack, S., Barban, M. A., Wadzinski, B. E., & Colbran, R. J.
- Affiliations
- Vanderbilt University (US)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1997-05
- Volume
- 68
- Issue
- 5
- Pages
- 2119-2128
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2113545093
- Cited by
- 299
- References
- 0
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 8 · 2022: 7 · 2021: 11 · 2020: 4 · 2019: 10 · 2018: 7 · 2017: 10 · 2016: 5 · 2015: 7 · 2014: 7 · 2013: 6 · 2012: 15
- FWCI
- 5.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vanderbilt University
- National Institutes of Health (5r29gm047973-05)
- National Institute of General Medical Sciences (GM47973, GM-51366)
- 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 › Protein Tyrosine Phosphatases
- Keywords
- CaMKII, protein phosphatase 1, protein phosphatase 2A, protein phosphatase 2C, calcineurin, postsynaptic density, dephosphorylation, subcellular compartmentalization, forebrain
- MeSH terms
- Animals, Cytoskeleton, Enzyme Activation, Isoenzymes, Phosphoprotein Phosphatases, Phosphorylation, Solubility, Subcellular Fractions, Synapses, Tissue Extracts, Prosencephalon, Calcium-Calmodulin-Dependent Protein Kinases, Rats
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