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

Overview

Journal J Neurosci

Specialty Neurology

Date 2002 Jun 1

PMID 12040039

Citations 72

Authors

Eleanor T Coffey

Giedre Smiciene

Vesa Hongisto

Jiong Cao

Stephan Brecht

Thomas Herdegen

Michael J Courtney

Affiliations

Soon will be listed here.

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.

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