A single c-Jun N-terminal kinase isoform (JNK3-p54) is an effector in both neuronal differentiation and cell death.
The c-Jun N-terminal kinases (JNKs) mediate degeneration and apoptosis in the brain. Particularly, JNK3 is considered to be a degenerative enzyme with c-Jun as a relevant substrate. The contribution of individual JNK isoforms, however, to pathological as well as to physiological processes remains to be defined. To analyze the effects of a single JNK isoform on neuronal cell death and differentiation, we transfected PC12 cells, which normally express only JNK1 and JNK2, with JNK3-p54. Transfected JNK3 significantly enhanced cell death after UV irradiation (0.5-6 J/cm(2)) and paclitaxel/taxol treatment (1-10 microm). In contrast, in the context of nerve growth factor-induced (10 or 50 ng/ml) differentiation of PC12 cells, JNK3 expression significantly increased the number and length of neurites. This functional dichotomy of JNK3 was mirrored by differential activation and induction of nuclear JNK substrates; although activating transcription factor-2 phosphorylation was enhanced by death signaling in response to UV and taxol, c-Jun protein expression and N-terminal phosphorylation were increased during nerve growth factor-induced differentiation. The absence of significant JNK activation or target phosphorylation in response to H(2)O(2) (60 microm) further supports the hypothesis that JNK isoforms are not merely injury- or stress-specific kinases but also have context-specific physiological functions.
Waetzig
Vicki
V
Institute of Pharmacology, Kiel University Medical Center, D-24105 Kiel, Germany.
Herdegen
Thomas
T
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D016923:Cell Death / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D048429:Cell Size; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D016877:Oxidants / Q000494:pharmacology; D016716:PC12 Cells; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D014466:Ultraviolet Rays
D000972:Antineoplastic Agents, Phytogenic; D007527:Isoenzymes; D016877:Oxidants; D020932:Nerve Growth Factor; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D017239:Paclitaxel