title: Oncogenes, protein kinase C, neuronal differentiation and memory.
abstract: The present article intends to substantiate the concept that protein kinase C signals are involved in apparently unrelated phenomena at the level of the nervous system, like rapid changes in cell excitability, long-term potentiation, learning, memory, and neuronal differentiation. While the involvement of the protein kinase C signal in memory-associated processes and synaptic plasticity is now supported by a variety of data, increasing evidence is emerging that neuronal differentiation in vitro is dependent on a protein kinase C signal, induced by Nerve Growth Factor, or, alternatively, by the activated oncogenes v-ras or v-src. These differentiative agents, as well as phorbol esters or membrane depolarization, are eventually able to elicit the expression of signal-sensitive genome trans-activators, like the nuclear oncogene c-fos. To propose a unitary model, we have chosen three examples among neuronal functions which imply the activation of protein kinase C: (i) rapid phosphorylation of ion channels by protein kinase C and transient changes in cell excitability; (ii) prolonged activation of the enzyme during long-term potentiation, which is a long-lasting increase in synaptic efficacy and has been related to learning and memory; (iii) the action of some oncogenes (e.g. v-ras and v-src) which act as differentiative agents in vitro through protein kinase C signals. They are an example to illustrate the likely involvement of this enzyme following expression of the cellular proto-oncogenes c-ras and c-src during the physiological steps of differentiation. We propose that the differences in the observed phenomena are due to the different time-windows in which the signal is offered, prolonged, repeated (or self-reinforced) to biological systems differing in potentiality and complexity.
authors.affiliation: Laboratory of Molecular Biology, Institute of General Pathology, University of Florence, Italy.
authors.forename: V P
authors.initials: VP
authors.lastname: Chiarugi
authors.forename: M
authors.initials: M
authors.lastname: Ruggiero
authors.forename: R
authors.initials: R
authors.lastname: Corradetti