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 kinase 2 (JNK2)/stress activated protein kinase (SAPK) in dose- and time-dependent manners in vitro. JNK2 activity is significantly decreased at 10 microM 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-terminal1-79 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.
So
H S
HS
Department of Microbiology & Immunology, Wonkwang University School of Medicine, Iksan Chonbuk, South Korea.
Park
R K
RK
Kim
M S
MS
Lee
S R
SR
Jung
B H
BH
Chung
S Y
SY
Jun
C D
CD
Chung
H T
HT
D017209:Apoptosis / Q000187:drug effects; D004229:Dithiothreitol / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D048670:MAP Kinase Kinase 4; D048056:Mitogen-Activated Protein Kinase 9; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000378:metabolism; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D026422:S-Nitrosoglutathione; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009603:Nitroso Compounds; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; C110881:S-nitro-N-acetylpenicillamine; D013439:Sulfhydryl Reagents; D009599:Nitroprusside; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D011494:Protein Kinases; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D005978:Glutathione; D010396:Penicillamine; D004229:Dithiothreitol