Calmodulin Trapping by Calcium-Calmodulin-Dependent Protein Kinase
Abstract
Multifunctional calcium-calmodulin-dependent protein kinase (CaM kinase) transduces transient elevations in intracellular calcium into changes in the phosphorylation state and activity of target proteins. By fluorescence emission anisotropy, the affinity of CaM kinase for dansylated calmodulin was measured and found to increase 1000 times after autophosphorylation of the threonine at position 286 of the protein. Autophosphorylation markedly slowed the release of bound calcium-calmodulin; the release time increased from less than a second to several hundred seconds. In essence, calmodulin is trapped by autophosphorylation. The shift in affinity does not occur in a site-directed mutant in which threonine at position 286 has been replaced by a non-phosphorylatable amino acid. These experiments demonstrate the existence of a new state in which calmodulin is bound to CaM kinase even though the concentration of calcium is basal. Calmodulin trapping provides for molecular potentiation of calcium transients and may enable detection of their frequency.
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After T286 autophosphorylation, the affinity for Ca2+/CaM increases more than 1,000-fold, from 15 nM to 20 pM.
“After T286 autophosphorylation, however, the autoinhibitory segment may be further displaced from the kinase surface so that the full CaM binding site becomes available (74, 89, 90) and the affinity for Ca2+/CaM increases >1,000-fold (from 15 nM to 20 pM) (91).”
From Synaptic memory and CaMKII (2023) · cites this paper as [91]
The increased affinity for Ca2+/CaM is due to a greatly reduced dissociation rate of Ca2+/CaM, referred to as CaM trapping.
“The increased affinity is due to a greatly reduced dissociation rate of Ca2+/CaM; it takes many seconds to dissociate when Ca2+ is elevated versus a fraction of a second before autophosphorylation and is referred to as CaM trapping (91, 92).”
From Synaptic memory and CaMKII (2023) · cites this paper as [91]
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- Authors
- Meyer, T., Hanson, P. I., Stryer, L., & Schulman, H.
- Affiliations
- Stanford Medicine (US)
- Venue
- Science
- Published
- 1992-05-22
- Volume
- 256
- Issue
- 5060
- Pages
- 1199-1202
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1998678953
- Cited by
- 637
- References
- 0
- Citations by year
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- FWCI
- 12.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2r01gm040600-10, 5r01mh045324-04)
- National Institute of Mental Health (MH-45324)
- National Institute of General Medical Sciences (GM-24032, GM40600)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- calcium/calmodulin-dependent protein kinase, autophosphorylation, calcium transients, calcium signaling, kinase regulation
- MeSH terms
- Amino Acid Sequence, Base Sequence, Binding, Competitive, Calcium, Calmodulin, Cell Line, Egtazic Acid, Kinetics, Molecular Sequence Data, Phosphorylation, Protein Binding, Protein Kinases, Recombinant Proteins, Spectrometry, Fluorescence, Threonine, Time Factors, Transfection, Mutagenesis, Site-Directed, Calcium-Calmodulin-Dependent Protein Kinases
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