Ca2+/calmodulin-dependent protein kinase
Ca2+/calmodulin-dependent protein kinases or CaM kinases (EC 184.108.40.206) 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.
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.