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PMID: 12040039 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

c-Jun N-terminal protein kinase (JNK) 2/3 is specifically activated by stress, mediating c-Jun activation, in the presence of constitutive JNK1 activity in cerebellar neurons.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 22 ·No. 11 ·2002-06-01 ·Pages 4335-45

Coffey ET, Smiciene G, Hongisto V, Cao J, Brecht S, Herdegen T, Courtney MJ

Abstract

c-Jun is considered a major regulator of both neuronal death and regeneration. Stress in primary cultured CNS neurons induces phosphorylation of c-Jun serines 63 and 73 and increased c-Jun protein. However, total c-Jun N-terminal protein kinase (JNK) activity does not increase, and no satisfactory explanation for this paradox has been available. Here we demonstrate that neuronal stress induces strong activation of JNK2/3 in the presence of constitutively and highly active JNK1. Correspondingly, neurons from JNK1(-/-) mice show lower constitutive activity and considerably higher responsiveness to stress. p38 activity can be completely inhibited without effect on c-Jun phosphorylation, whereas 10 micrometer SB203580 strongly inhibits neuronal JNK2/3, stress-induced c-Jun phosphorylation, induced c-Jun activity, and neuronal death in response to trophic withdrawal stress. Neither constitutive JNK1 activity nor total neuronal JNK activity were significantly affected by this concentration of drug. Thus, neuronal stress selectively activates JNK2/3 in the presence of mechanisms maintaining constitutive JNK1 activity, and this JNK2/3 activity selectively targets c-Jun, which is isolated from constitutive JNK1 activity.

MeSH Terms
Animals Cell Compartmentation Cells, Cultured Cerebellum/cytology,drug effects,enzymology Dose-Response Relationship, Drug Enzyme Activation/drug effects,physiology Enzyme Inhibitors/pharmacology Genes, Reporter Growth Substances/pharmacology Imidazoles/pharmacology Isoenzymes/antagonists & inhibitors,genetics,metabolism JNK Mitogen-Activated Protein Kinases Mice Mice, Knockout Mitogen-Activated Protein Kinase 10 Mitogen-Activated Protein Kinase 8 Mitogen-Activated Protein Kinase 9 Mitogen-Activated Protein Kinases/antagonists & inhibitors,genetics,metabolism Neurons/cytology,drug effects,enzymology Phosphorylation/drug effects Promoter Regions, Genetic Protein-Tyrosine Kinases/antagonists & inhibitors,metabolism Pyridines/pharmacology Rats Recombinant Fusion Proteins/genetics,metabolism Stress, Physiological/enzymology p38 Mitogen-Activated Protein Kinases
Chemicals
Enzyme Inhibitors Growth Substances Imidazoles Isoenzymes Pyridines Recombinant Fusion Proteins Mitogen-Activated Protein Kinase 10 Mitogen-Activated Protein Kinase 9 Protein-Tyrosine Kinases JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinase 8 Mitogen-Activated Protein Kinases p38 Mitogen-Activated Protein Kinases SB 203580
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Coffey Eleanor T
Department of Biochemistry and Pharmacy Abo Akademi University, Biocity, Turku, FIN 20521, Finland.
Smiciene Giedre
Hongisto Vesa
Cao Jiong
Brecht Stephan
Herdegen Thomas
Courtney Michael J
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
20026401
Published
2002-06-01
Pages
4335-45
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6758801
Subset
IM
External Links
PubMed source DOI: 20026401 PMC Full Text View journal details
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