PREVIOUS study has shown that the treatment of PC12 cells with manganese, a MPTP-like neurotoxin, causes transcription-dependent apoptosis. This is a useful model system for the study of neuronal cell death. Manganese-induced apoptosis is accompanied by the induction of DNA fragmentation, expressions of c-Fos and c-Jun, and activation of the c-Jun N-terminal kinase (JNK) pathway. Here, we report that manganese induces phosphorylation of p70 S6 kinase at Ser411 and Thr421/Ser424, and activates the enzyme. Thus, phosphorylation and activation of p70 S6 kinase are accompanied by transcription-dependent apoptosis, suggesting a role for p70 S6 kinase in this type of apoptosis.