Pharmacological Research 54 (2006) 317–325 Review The different facets of protein kinases C: old and new players in neuronal signal transduction pathways Marialaura Amadio a , Fiorenzo Battaini b , Alessia Pascale a,∗ a Department of Experimental and Applied Pharmacology, University of Pavia, Pavia, Italy b Department of Neuroscience, University of Roma “Tor Vergata”, Roma, Italy Accepted 8 August 2006 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 compart- ments, 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). © 2006 Elsevier Ltd. All rights reserved. Keywords: PKC; RACK1; ELAV proteins; Memory; Aging and Alzheimer’s disease Contents 1. Introduction ............................................................................................................ 317 2. PKC family and the importance of the interaction with scaffolding proteins ................................................... 318 3. Role of PKCs within some cellular functions ............................................................................... 320 3.1. Nuclear activities ................................................................................................. 320 3.2. Neurotransmission ................................................................................................ 321 3.3. Hypotheses on the involvement of ELAVs in memory and on their relationship with PKC ................................ 321 3.4. Physiological and pathological aging target PKC pathway ............................................................. 322 4. Conclusion ............................................................................................................. 323 Acknowledgments ...................................................................................................... 323 References ............................................................................................................. 323 1. Introduction The flow of information from the outside to the inside of the cell and vice versa allows each cell to adapt to continual changes ∗ Corresponding author. Tel.: +39 0382 987 963; fax: +39 0382 987 405. E-mail addresses: battaini@med.uniroma2.it (F. Battaini), alessia.pascale@unipv.it (A. Pascale). and requests coming from the external environment, and to maintain a general equilibrium. Among the multiple molecular systems belonging to the so-called signal transduction process, the proteins phosphorylation and dephosphorylation represent a versatile mechanism to mediate cellular responses. The two main classes of enzymes controlling these processes are on one side the protein kinases, which catalyse the phosphotransfer reaction, and on the other side the phosphatases, which are implicated in 1043-6618/$ – see front matter © 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.phrs.2006.08.002