The different facets of protein kinases C: old and new players in neuronal signal transduction pathways

Abstract

Signal transduction pathways are crucial for cell-to-cell communication. Various molecular cascades allow the translation of distinct stimuli, targeting the cell, into a language that the cell itself is able to understand, thus elaborating specific responses. Within this context, a strategic role is played by protein kinases which catalyze the phosphorylation of specific substrates. The serine/threonine protein kinase C (PKC) enzymes family (at least 10 isoforms) is implicated in the transduction of signals coupled to receptor-mediated hydrolysis of membrane phospholipids. Within this molecular pathway, protein-protein interactions play a critical role in directing the distinct activated PKCs towards selective subcellular compartments, in order to guarantee spatio-temporal and localized cellular responses. A space-specific modulation of biochemical events is particularly important during learning. Among the various mechanisms, the modulation of mRNA decay appears to be an efficient post-transcriptional way of controlling gene expression during learning, allowing changes to take place in selected neuronal regions, in particular at synaptic level. To this regard, recent studies have pointed out that PKC activation is also involved in a novel signalling cascade leading to the stabilization of specific mRNAs. This review will especially focus the attention on the implication of PKC in memory trace formation and how alterations within this molecular cascade may have consequences on physiological and pathological neuronal aging (i.e. Alzheimer's disease).