Nitric oxide inhibits c-Jun N-terminal kinase 2 (JNK2) via S-nitrosylation

S-nitrosylation by S-nitrosoglutathione (GSNO), a nitric oxide (NO) donor, suppresses the phosphotransferase activity of cJun N-terminal kinase2 (JNK2)/stress activated protein kinase (SAPK) in dose- and time-dependent manners in vitro. JNK2 activity is significantly decreased at 10 mu M 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, GrSNO-treated Sek1 does not affect the JNK2 activity of phosphotransferation toward c-Jun N-terminal(1-79) protein. 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. (C) 1998 Academic Press.S-nitrosylation by S-nitrosoglutathione (GSNO), a nitric oxide (NO) donor, suppresses the phosphotransferase activity of cJun N-terminal kinase2 (JNK2)/stress activated protein kinase (SAPK) in dose- and time-dependent manners in vitro. JNK2 activity is significantly decreased at 10 mu M 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(1-79) protein. 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. (C) 1998 Academic Press.