Nitric Oxide Inhibits c-Jun N-Terminal Kinase 2 (JNK2) via S-Nitrosylation

• Published in: Biochemical and biophysical research communications 1998-06, Vol.247 (3), p.809-813
• Main Authors: So, H.S., Park, R.K., Kim, M.S., Lee, S.R., Jung, B.H., Chung, S.Y., Jun, C.D., Chung, H.T.
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Dithiothreitol - pharmacology; Enzyme Inhibitors - pharmacology; Glutathione - analogs & derivatives; Glutathione - metabolism; Glutathione - pharmacology; Humans; MAP Kinase Kinase 4; Mitogen-Activated Protein Kinase 9; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; Nitric Oxide - pharmacology; Nitroprusside - pharmacology; Nitroso Compounds - metabolism; Penicillamine - analogs & derivatives; Penicillamine - pharmacology; Phosphorylation; Protein Kinases - metabolism; Proto-Oncogene Proteins c-jun - metabolism; Recombinant Proteins - metabolism; S-Nitrosoglutathione; Sulfhydryl Reagents - pharmacology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1998.8788

S-nitrosylation by S-nitrosoglutathione (GSNO), a nitric oxide (NO) donor, suppresses the phosphotransferase activity of cJun N-terminal kinase 2 (JNK2)/stress activated protein kinase (SAPK) in dose- and time-dependent manners in vitro.JNK2 activity is significantly decreased at 10 μM of GSNO, which is dramatically reversed by adding 10 mM of DTT. Reduced form of glutathione protects the GSNO-induced suppression of JNK2 activation in a dose-dependent fashion. However, GSNO-treated Sek1 does not affect the JNK2 activity of phosphotransferation toward c-Jun N-terminal 1-79protein. These results indicate that NO may exert a regulatory role of JNK2 activity by S-nitrosylation of the protein in apoptotic signaling pathway. Suppression of JNK2 phosphotransferase activity by NO is also supported by the observation that NO plays an important anti-apoptotic roles in heptocytes, splenocytes, eosinophils and B lymphocytes.