The impact of the distribution of isoforms on CaMKII activation

We have developed a computational model of the regulation of αα- and ββ-CaMKII activity, in order to examine (i) the importance of neighbour subunit interactions and (ii) the effect the higher CaMCa4 affinity of ββ-CaMKII has on the holoenzyme activity in different configurations with the same α:βα:β ratio. The model consists of a deterministic biochemical network coupled to stochastic activation of CaMKII. The results suggest that CaMKII holoenzyme activity is non-linear and dependent on the holoenzyme configuration of isoforms. This is especially pronounced in situations with a high-dephosphorylation rate of CaMKII.