Phosphorylation and activation of p70 S6 kinase by manganese in PC12 cells.
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 U(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.
Hirata
Y
Y
Laboratory for Genes of Motor Systems, Bio-Mimetic Control Research Center, The Institute of Physical and Chemical Research (RIKEN), Moriyama, Nagoya, Japan.
Adachi
K
K
Kiuchi
K
K
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D000906:Antibodies / Q000378:metabolism; D000918:Antibody Specificity; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites / Q000187:drug effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002166:Camptothecin / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D015151:Immunoblotting; D048031:JNK Mitogen-Activated Protein Kinases; D008345:Manganese / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D051381:Rats; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D013912:Threonine / Q000378:metabolism
D000906:Antibodies; D019253:Proto-Oncogene Proteins c-bcl-2; D013912:Threonine; D008345:Manganese; D012694:Serine; D000841:Anisomycin; D003513:Cycloheximide; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D019311:Staurosporine; D002945:Cisplatin; D002166:Camptothecin