PMID- 14597634 OWN - NLM STAT- MEDLINE DCOM- 20040423 LR - 20220311 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 279 IP - 4 DP - 2004 Jan 23 TI - Cytosolic peroxiredoxin attenuates the activation of Jnk and p38 but potentiates that of Erk in Hela cells stimulated with tumor necrosis factor-alpha. PG - 2535-43 AB - 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. FAU - Kang, Sang Won AU - Kang SW AD - Laboratory of Cell Signaling, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. FAU - Chang, Tong-Shin AU - Chang TS FAU - Lee, Tae-Hoon AU - Lee TH FAU - Kim, Eun Seon AU - Kim ES FAU - Yu, Dae-Yeul AU - Yu DY FAU - Rhee, Sue Goo AU - Rhee SG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20031103 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.11.1.- (Peroxidases) RN - EC 1.11.1.15 (Peroxiredoxins) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 2.7.12.2 (MAP Kinase Kinase 4) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) SB - IM MH - Cytosol/metabolism MH - Enzyme Activation/drug effects MH - HeLa Cells MH - Humans MH - *JNK Mitogen-Activated Protein Kinases MH - MAP Kinase Kinase 4 MH - Mitogen-Activated Protein Kinase Kinases/*metabolism MH - Mitogen-Activated Protein Kinases/*metabolism MH - Peroxidases/*metabolism MH - Peroxiredoxins MH - Signal Transduction/drug effects MH - Tumor Necrosis Factor-alpha/*metabolism MH - p38 Mitogen-Activated Protein Kinases EDAT- 2003/11/05 05:00 MHDA- 2004/04/24 05:00 CRDT- 2003/11/05 05:00 PHST- 2003/11/05 05:00 [pubmed] PHST- 2004/04/24 05:00 [medline] PHST- 2003/11/05 05:00 [entrez] AID - S0021-9258(18)52617-X [pii] AID - 10.1074/jbc.M307698200 [doi] PST - ppublish SO - J Biol Chem. 2004 Jan 23;279(4):2535-43. doi: 10.1074/jbc.M307698200. Epub 2003 Nov 3.