Ras-dependence of nerve growth factor-induced inhibition of proliferation of PC12 cells

The PC12 rat phaeochromocytoma cell line is the most frequently used model system to study neuronal differentiation: nerve growth factor (NGF) inhibit s proliferation and causes easily scorable neurite formation in these cells . The central role of the monomeric guanine nucleotide binding Ras proteins in the pathway of NGF-induced differentiation is well documented. However, the possible involvement of Ras proteins in signal transduction processes mediating NGF-induced inhibition of proliferation has not been analyzed. To address this problem we studied PC12 subclones expressing a dominant inhib itory mutant Ras protein (Ha-Ras Asn17). Our results indicate that the cell cycle arrest characteristic of NGF-treated PC12 cells is mediated by a Ras -dependent signaling mechanism.