Sequences of autophosphorylation sites in neuronal type II CaM kinase that control Ca2+-independent activity
Abstract
After initial activation by Ca2+, the catalytic activity of type II Ca2+/calmodulin-dependent protein kinase rapidly becomes partially independent of Ca2+. The transition is caused by autophosphorylation of a few subunits in the dodecameric holoenzyme, which is composed of varying proportions of two homologous types of subunits, alpha (50 kd) and beta (58-60 kd). We have identified one site in the alpha subunit (Thr286) and two in the beta subunit (Thr287 and Thr382) that are rapidly autophosphorylated. We show that phosphorylation of alpha-Thr286 and beta-Thr287, which are located immediately adjacent to the calmodulin binding domain, controls Ca2(+)-independent activity. In contrast, phosphorylation of beta-Thr382 is not required to maintain Ca2+ independence. It is absent in the alpha subunit and is selectively removed from the minor beta' subunit, apparently by alternative splicing. Regulation of the presence of beta-Thr382 in the holoenzyme by both differential gene expression and alternative splicing suggests that it may have an important but highly specialized function.
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T286 autophosphorylation is primarily intersubunit within a holoenzyme, although at very high kinase concentration it can also occur by an interholoenzyme mechanism.
“This autophosphorylation is primarily intersubunit autophosphorylation within a holoenzyme, although at very high kinase concentration it can also occur by an interholoenzyme mechanism (FIGURE 2B4) (71, 79–81).”
From Synaptic memory and CaMKII (2023) · cites this paper as [79]
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- Authors
- Miller, S. G., Patton, B. L., & Kennedy, M. B.
- Affiliations
- California Institute of Technology (US)
- ORCID
- Kennedy, Mary B.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1988-09
- Volume
- 1
- Issue
- 7
- Pages
- 593-604
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2067529350
- Cited by
- 279
- References
- 1
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 7 · 2019: 4 · 2018: 6 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 5 · 2013: 6 · 2012: 3
- FWCI
- 5.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS-17660, NS-07251)
- 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 › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Keywords
- autophosphorylation sites, calmodulin-binding domain, alpha subunit, beta subunit, alternative splicing
- MeSH terms
- Animals, Brain, Brain Chemistry, Calcium, Cattle, Phosphorylation, Protein Kinases, Calcium-Calmodulin-Dependent Protein Kinases, In Vitro Techniques
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