ACTIONS AND REGULATION OF PROTEIN-KINASE-C IN BRAIN

Protein kinase C (PKC), a phospholipid- and Ca 2+-dependent protein kinase, plays crucial roles in transmitting biochemical signals from the surface and transducing them to the interior of cells. PKC participates in a wide spectrum of neuronal processes including neuronal development, modulation of ion channel activity and signal transduction system, neurotransmitter synthesis and release, and synaptic plasticity. The PKC family consists of originally described alpha-betaI-, betaII-, and gammaPKC (Group A enzymes) and the recently identified but less characterized delta, epsilon, zeta, and eta (L) PKC (Group B enzymes) . Protein kinase C possesses a regulatory domain with one or more zinc finger-like structures and a basic pseudo substrate prototype. Various growth factors, neurotransmitters, and hormones elicit the breakdown of inositol 1,4,5 triphosphate to produce diacylglycerol and inositol 1,4,5 triphosphate, which in turn results in mobilization of calcium from intracellular stores. Group A enzymes are activated by calcium, phospholipid, and diacylglycerol, whereas the Group B enzymes are calcium independent. Zinc enhances the activity of protein kinase C and activation of protein kinase C leads to induction of metallothionein mRNA. Some members of the PKC family exhibit unique patterns of tissue expression and intracellular localization. Different kinases have distinct functions in the processing and modulation of a variety of physiological and pathological responses to external signals. For example, protein kinase C is able to phosphorylate Alzheimer amyloid precursor protein, and betaII PKC is reduced in the striatum of patients with Huntington's disease. Moreover, PKC modulates NMDA current, and has been linked to induction of long term potentiation, to memory formation, and cognition.