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The phosphorylated enzymes are then activated by activator protein. Thus, the activation
occurs in two steps, and a new mechanism of enzyme regulation is proposed; first,
phosphorylation of TH and TPH by CaMKII, and second, activation of the phosphorylated
enzymes by the activator protein (Yamauchi & Fujisawa,1981; Yamauchi et al., 1981;
Yamauchi, 2005). Currently, the activator protein is known to be the same protein as 14-3-3
protein, and to be a regulator of the signal transduction/phosphorylation mechanism. Since
these monoamines are known to be involved in normal mental function or in some
neurological diseases, CaMKII may play an important role in mental function.
Table 2. CaMKII substrates and interacting proteins, and their regulation by CaMKII
in the presynapse
1, Yamauchi, 2005; 2, Benfenati et al., 1992; 3, Singh et al., 1996; 4, Verona, et al., 2000; 5, Ohyama et
al., 2002.
4-2. Synaptic vesicle proteins
CaMKII phosphorylates synaptic vesicle proteins, such as synapsin I and synaptotagmin.
Synapsin I is a synaptic vesicle-associated phosphoprotein that is involved in the modulation
of neurotransmitter release.CaMKII phosphorylates synapsin I, causes synapsin I to dissociate
from synaptic vesicles, and increases neurotransmitter release (Benfenati et al., 1992 ).
Synaptotagmin is associated with CaMKII, resulting in stimulation of the formation of fusion
complex (Verona et al., 2000).
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