CaM-kinase II

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CaM-kinase II (Ca2+/calmodulin-dependent kinase II, CAMK2) is a widely expressed kinase in the central nervous system that is found in the postsynaptic density (PSD). It has roles in the CaMK cascade in the nervous system and immune system if not elsewhere by suspicion or analogy such as muscle and endocrine system. The similar protein in mice is involved in regulating short term memory[1] and it is associated with the NMDA receptor complex in excitatory synapses. It is composed of four different chains:

  1. Calcium/calmodulin-dependent protein kinase type II alpha chain coded by CAMK2A gene
  2. Calcium/calmodulin-dependent protein kinase type II beta chain coded by the CAMK2B gene
    • 7 isoforms expressed in adult and fetal brain.
    • Been associated with short term fear memory
  3. Calcium/calmodulin-dependent protein kinase type II gamma chain coded by the CAMK2G gene at 10q22
    • 6 isoforms, some expressed in beta islet cells and (Memory !) T cells.
    • Genetic variations in man have been related to short-term episodic memory performance
  4. Calcium/calmodulin-dependent protein kinase type II delta chain coded by the CAMK2D gene
    • 9 isoforms expressed in skeletal and cardiac muscle

Function

The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 8 to 12 subunits. There are roles in cell proliferation and apoptosis, neuronal growth and CNS development, synaptic plasticity, memory formation and maintenance; immune function such as the inflammatory response, activation of T lymphocytes and hematopoietic function and hormonal energy balance. Interaction with the NMDA receptor subunit NR2B allows in hippocampal neurons the glutamate-induced translocation of the kinase to the synapse.The modulation by synaptic calcium, inhibitory autophosphorylation of CaM-kinase II and most importantly direct generation of a sustained calcium/calmodulin-independent kinase activity has key roles in signaling after NMDA receptor activation. There seems to be feedback by an interaction that leads to trapping of calmodulin that reduces downregulation of the NMDA receptor.