c-Jun promotes neurite outgrowth and survival in PC12 cells.
We investigated the function of c-Jun in PC12 cells by transfecting them with a plasmid containing a c-Jun cDNA transcription cassette. Transfected cells expressed high levels of c-Jun mRNA and protein and demonstrated an increase in both AP-1 DNA binding and gene activation. The c-Jun over-expressing cells showed marked neurite outgrowth but no evidence of spontaneous cell death. In fact, c-Jun over-expressing cells were more resistant to okadaic acid-induced apoptosis. The process outgrowth was not indicative of a full neuronal differentiation response as the transfected PC12 cells did not display action potentials when examined with whole-cell patch-clamping. The phosphorylation of c-Jun on serine 73 appears to be important for this neurite sprouting effect as mutagenesis at this site reduced sprouting whereas a serine 63 mutant tended to increase sprouting. Thus, in PC12 cells c-Jun expression does not induce apoptosis, but rather functions as a neurite outgrowth and neuronal survival signal.
Dragunow
M
M
Department of Molecular Medicine, Faculty of Medicine and Health Science, The University of Auckland, Private Bag 92019, Auckland, New Zealand. m.dragunow@auckland.ac.nz
Xu
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R
Walton
M
M
Woodgate
A
A
Lawlor
P
P
MacGibbon
G A
GA
Young
D
D
Gibbons
H
H
Lipski
J
J
Muravlev
A
A
Pearson
A
A
During
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D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure*; D019319:Okadaic Acid / Q000494:pharmacology; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D010641:Phenotype; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D015222:Sodium Channels / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000502:physiology; D014162:Transfection
D004791:Enzyme Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D015222:Sodium Channels; D018808:Transcription Factor AP-1; D019319:Okadaic Acid; D020932:Nerve Growth Factor; D008156:Luciferases