Ca2+/calmodulin-dependent protein kinase

Ca2+/calmodulin-dependent protein kinases  or CaM kinases are serine/threonine-specific protein kinase are primarily regulated by the Ca2+/calmodulin complex. These kinases show a memory effect on activation.

Types
Two types of CaM kinase are:
 * Specialized CaM kinases. An example is the myosin light chain kinase (MLCK) that phosphorylates myosin, causing muscles to contract.
 * Multifunctional CaM kinases. Also collectively called CaM kinase II, which play a role in many processes, such as neurotransmitter secretion, transcription factor regulation, and glycogen metabolism. Between 1% and 2% of the proteins in the brain are CaM kinase II.

Structure and autoregulation
The CaM kinases consist of an N-terminal catalytic domain, a regulatory domain, and an association domain. The enzymes assemble into dodecameric holoenzyme structures, with the catalytic domains sticking out, such that these may phosphorylate residues in an intersubunit fashion. In the absence of Ca2+/calmodulin, the catalytic domain is autoinhibited by the regulatory domain, which contains a pseudosubstrate sequence. Several CaM kinases aggregate into a homooligomer or heterooligomer. Upon activation by Ca2+/calmodulin, the activated CaM kinases autophosphorylate each other in an intermolecular reaction at the threonine 286 residue. This has two effects:


 * 1) An increase in affinity for the calmodulin complex, prolonging the time the kinase is active.
 * 2) Autonomic activity of the phosphorylated kinase complex even after the calmodulin complex has dissociated from the kinase complex, which prolongs the active state even more.

Phosphorylation at residues 305/306, which are both threonines, have a negative effect on binding of Ca2+/calmodulin complex to enzyme subunits, thus reducing function.

The introduction of phospho-mimicking and phospho-null mutations of the enzyme at these sites into mice have shown that both mutations have effects on the way that long term memory is induced.

Genes

 * CaMK I - CAMK1, CAMK1D, CAMK1G
 * CaMK II - CAMK2A, CAMK2B, CAMK2D, CAMK2G
 * CaMK IV - CAMK4