Nitric oxide (NO) has been shown to negatively regulate c-Jun N-terminal kinase (JNK) through S-nitrosylation. Here, we show that disruption of an interaction between JNK and its substrate c-Jun is an important mechanism underlying the NO-mediated inhibition of JNK signaling. Endogenous NO, which was generated by interferon-γ treatment, suppressed anisomycin-stimulated JNK activity in microglial BV-2 cells. The interferon-γ-induced suppression of JNK1 activation in BV-2 cells was prevented completely by treatment with NG-nitro-l-arginine, an inhibitor of NO synthase. A NO donor S-nitro-N-acetyl-dl-penicillamine (SNAP) inhibited JNK activity in vitro, and this inhibition was reversed by a thiol-reducing agent, dithiothreitol. Nitric oxide disrupts a physical interaction between JNK and its substrate c-Jun both in vitro and in intact cells without affecting an interaction between SEK1 and JNK. Collectively, our results suggest that the inhibition of the interaction between JNK and c-Jun may be an integral part of the mechanism underlying the negative regulation of the JNK signaling pathway by NO.
|Number of pages
|Biochemical and biophysical research communications
|Published - 2006 Dec 8
Bibliographical noteFunding Information:
We thank Dr. R.J. Davis for JNK cDNAs, and Dr. L.I. Zon for SEK1 cDNA. This work was supported by the Molecular and Cellular BioDiscovery Research Program Grant (M10601000136-06N0100-13610) from the Ministry of Science and Technology, South Korea (E.-J.C.) and Korea Research Foundation Grant (KRF-1999-005-C00026) funded by the Korean Government (H.-S..P).
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology