Activation State-Dependent Substrate Gating in Ca²⁺/Calmodulin-Dependent Protein Kinase II.

ABSTRACT: Calcium/calmodulin-dependent protein kinase II (CaMKII) is highly concentrated in the brain where its activation by the Ca²⁺ sensor CaM, multivalent structure, and complex autoregulatory features make it an ideal translator of Ca²⁺ signals created by different patterns of neuronal activity. We provide direct evidence that graded levels of kinase activity and extent of T²⁸⁷ (T²⁸⁶α isoform) autophosphorylation drive changes in catalytic output and substrate selectivity. The catalytic domains of CaMKII phosphorylate purified PSDs much more effectively when tethered together in the holoenzyme versus individual subunits. Using multisubstrate SPOT arrays, high-affinity substrates are preferentially phosphorylated with limited subunit activity pe

SUBMITTER: Johnson DE 

PROVIDER: S-EPMC5748111 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature