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CaMKII autonomy is substrate-dependent and further stimulated by Ca2+/calmodulin.

ABSTRACT: A hallmark feature of Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) regulation is the generation of Ca(2+)-independent autonomous activity by Thr-286 autophosphorylation. CaMKII autonomy has been regarded a form of molecular memory and is indeed important in neuronal plasticity and learning/memory. Thr-286-phosphorylated CaMKII is thought to be essentially fully active ( approximately 70-100%), implicating that it is no longer regulated and that its dramatically increased Ca(2+)/CaM affinity is of minor functional importance. However, this study shows that autonomy greater than 15-25% was the exception, not the rule, and required a special mechanism (T-site binding; by the T-substrates AC2 or NR2B). Autonomous activity toward regular R-substrates (including tyrosine hydroxylase and GluR1) was significantly further stimulated by Ca(2+)/CaM, both in vitro and within cells. Altered K(m) and V(max) made autonomy also substrate- (and ATP) concentration-dependent, but only over a narrow range, with remarkable stability at physiological concentrations. Such regulation still allows molecular memory of previous Ca(2+) signals, but prevents complete uncoupling from subsequent cellular stimulation.

SUBMITTER: Coultrap SJ

PROVIDER: S-EPMC2878555 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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CaMKII autonomy is substrate-dependent and further stimulated by Ca2+/calmodulin.

Coultrap Steven J SJ Buard Isabelle I Kulbe Jaqueline R JR Dell'Acqua Mark L ML Bayer K Ulrich KU

The Journal of biological chemistry 20100330 23

A hallmark feature of Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) regulation is the generation of Ca(2+)-independent autonomous activity by Thr-286 autophosphorylation. CaMKII autonomy has been regarded a form of molecular memory and is indeed important in neuronal plasticity and learning/memory. Thr-286-phosphorylated CaMKII is thought to be essentially fully active ( approximately 70-100%), implicating that it is no longer regulated and that its dramatically increased Ca(2+)/C ...[more]

PMID: 20353941

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CaMKII autonomy is substrate-dependent and further stimulated by Ca2+/calmodulin.

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CaMKII autonomy is substrate-dependent and further stimulated by Ca2+/calmodulin.

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