Ca2+/calmodulin-dependent protein kinase

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Ca2+/calmodulin-dependent protein kinases or CaM kinases (EC 2.7.11.17) are serine/threonine-specific protein kinase are primarily regulated by the Ca²⁺/calmodulin complex. These kinases show a memory effect on activation. Two types of CaM kinases 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.

[edit] Structure and autoregulation

The CaM kinases consist of an N-terminal catalytic domain, a regulatory domain, and an association domain. 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. This has two effects:

An increase in affinity for the calmodulin complex, prolonging the time the kinase is active.
Continued activation of the phosphorylated kinase complex even after the calmodulin complex has dissociated from the kinase complex, which prolongs the active state even more.