Regulation of brain Ca2+/calmodulin-dependent protein kinase II.

CaM-kinase II is a multifunctional protein kinase highly enriched in neural tissues where it modulates a variety of Ca2(+)-dependent processes. A complex regulatory domain in the kinase within residues 281-309 contains an autoinhibitory sequence, a CaM-binding region, and sites of regulatory autophosphorylation. Autophosphorylation on Thr286 converts the kinase to a Ca2(+)-independent form which could prolong physiological systems controlled by this kinase in response to transient Ca2+ elevations. Such properties appear to exist in dynamic equilibrium in the isolated postsynaptic density and in cultured brain cells. These unique biochemical regulatory properties, coupled with an unusual high concentration in the postsynaptic density of excitatory synapses, makes CaM-kinase II an attractive candidate for involvement in synaptic plasticity.