Protein kinase C alpha and Protein kinase C epsilon (PKCα and PKCε)

Protein kinase C (PKC) alpha and epsilon are serine/threonine kinases belonging to the classical and novel PKC subfamilies, respectively. They function as key nodes in signal transduction pathways regulating synaptic plasticity, gene expression, and cell survival (UniProt P17252, Q02156). In neuropsychiatry, these isozymes are recognized as critical downstream targets of mood-stabilizing drugs. Specifically, chronic administration of valproic acid (VPA) has been shown to selectively downregulate the protein levels and catalytic activity of PKC alpha and epsilon in the brain's frontal cortex and hippocampus (Manji et al., 2000, PMID: 10771011). This downregulation is hypothesized to mitigate the overactive intracellular signaling associated with manic episodes in bipolar disorder (Yuan et al., 1998, PMID: 9853702). Additionally, these isozymes are frequently dysregulated in various cancers, where PKC alpha often acts as a promoter of cell migration and PKC epsilon functions as a transforming oncogene. Consequently, they are targets for therapeutic intervention in both psychiatric conditions and oncology, with drugs like VPA acting as indirect modulators and others like bryostatin-1 acting as direct ligands.

Other names

PRKCAPRKCEPKC-alphaPKC-epsilonnPKC-epsiloncPKC-alphaProtein kinase C alpha typeProtein kinase C epsilon type

Chronic downregulation of the protein expression and catalytic activity of PKC alpha and epsilon isozymes, leading to stabilized neuronal signaling and altered synaptic plasticity.