Cytosolic peroxiredoxin attenuates the activation of Jnk and p38 but potentiates that of Erk in Hela cells stimulated with tumor necrosis factor-alpha.
Tumor necrosis factor-alpha (TNF-alpha) induces the activation of all three types of mitogen-activated protein kinase (MAPK): c-Jun NH(2)-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK). This cytokine also induces the production of several types of reactive oxygen species, including H(2)O(2). With the use both of HeLa cells expressing wild-type or dominant negative forms of the cytosolic peroxidase peroxiredoxin II and of mouse embryonic fibroblasts deficient in this protein, we evaluated the roles of H(2)O(2) in the activation of MAPKs by TNF-alpha. In vitro kinase assays as well as immunoblot analysis with antibodies specific for activated MAPKs indicated that H(2)O(2) produced in response to TNF-alpha potentiates the activation of JNK and p38 induced by this cytokine but inhibits that of ERK. Our results also suggest that cytosolic peroxiredoxins are important regulators of TNF signaling pathways.
Laboratory of Cell Signaling, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA.
Sang Won
SW
Kang
Tong-Shin
TS
Chang
Tae-Hoon
TH
Lee
Eun Seon
ES
Kim
Dae-Yeul
DY
Yu
Sue Goo
SG
Rhee
D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism*; D054464:Peroxiredoxins; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D014409:Tumor Necrosis Factor-alpha; D010544:Peroxidases; D054464:Peroxiredoxins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases