Identification of a Phosphorylation Site for Calcium/Calmodulindependent Protein Kinase II in the NR2B Subunit of the N-Methyl-D-aspartate Receptor
Open accessAbstract
The N-methyl-D-aspartate (NMDA) subtype of excitatory glutamate receptors plays critical roles in embryonic and adult synaptic plasticity in the central nervous system. The receptor is a heteromultimer of core subunits, NR1, and one or more regulatory subunits, NR2A-D. Protein phosphorylation can regulate NMDA receptor function (Lieberman, D. N., and Mody, I. (1994) Nature 369, 235-239; Wang, Y. T., and Salter, M. W. (1994) Nature 369, 233-235; Wang, L. -Y., Orser, B. A., Brautigan, D. L., and MacDonald, J. F. (1994) Nature 369, 230-232). Here we identify a major phosphorylation site on subunit NR2B that is phosphorylated by Ca2+/calmodulin-dependent protein kinase II (CaM kinase II), an abundant protein kinase located at postsynaptic sites in glutamatergic synapses. For the initial identification of the site, we constructed a recombinant fusion protein containing 334 amino acids of the C terminus of the NR2B subunit and phosphorylated it with CaM kinase II in vitro. By peptide mapping, automated sequencing, and mass spectrometry, we identified the major site of phosphorylation on the fusion protein as Ser-383, corresponding to Ser-1303 of full-length NR2B. The Km for phosphorylation of this site in the fusion protein was approximately 50 nM, much lower than that of other known substrates for CaM kinase II, suggesting that the receptor is a high affinity substrate. We show that serine 1303 in the full-length NR2B and/or the cognate site in NR2A is a major site of phosphorylat…
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Phosphorylation at S1303 promotes slow dissociation of CaMKII.
“however, phosphorylation at S1303 does promote slow dissociation of CaMKII (123, 125, 126).”
From Synaptic memory and CaMKII (2023) · cites this paper as [123]
CaMKII phosphorylates S1303 in the CTD.
“In addition to forming a complex with GluN2B, CaMKII phosphorylates S1303 (123) in the CTD.”
From Synaptic memory and CaMKII (2023) · cites this paper as [123]
A fragment of GluN2B is a substrate for CaMKII.
“a fragment of GluN2B is a substrate for CaMKII (123).”
From Synaptic memory and CaMKII (2023) · cites this paper as [123]
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- Authors
- Omkumar, R. V., Kiely, M. J., Rosenstein, A. J., Min, K.-T., & Kennedy, M. B.
- Affiliations
- California Institute of Technology (US)
- Corresponding author
- Kennedy, Mary B.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1996-12
- Volume
- 271
- Issue
- 49
- Pages
- 31670-31678
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2152541148
- Cited by
- 304
- References
- 3
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 10 · 2020: 10 · 2019: 2 · 2018: 6 · 2017: 7 · 2016: 4 · 2015: 9 · 2014: 10 · 2013: 9 · 2012: 19
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Scholarworks@UNIST (Ulsan National Institute of Science and Technology) (submittedVersion)
- Funders
- National Institutes of Health (5p50mh049176-10)
- National Institute of Mental Health (MH49176)
- National Institute of Neurological Disorders and Stroke (R01NS028710, R01NS017660, NS-17660, NS28710)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- NMDA receptor, NR2B subunit, calcium/calmodulin-dependent protein kinase II, protein phosphorylation, phosphorylation site identification, glutamate receptors, postsynaptic density, hippocampal neurons, synaptic plasticity, NR2A
- MeSH terms
- Animals, Binding Sites, Chromatography, High Pressure Liquid, Glutathione, Kinetics, Peptide Mapping, Phosphorylation, Serine, Mass Spectrometry, Trypsin, Receptors, N-Methyl-D-Aspartate, Calcium-Calmodulin-Dependent Protein Kinases, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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