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| Content Provider | Journal of Biological Chemistry (JBC) |
|---|---|
| Author | Carballo, Modesto Conde, Manuel Bekay, Rajaa El Martı́n-Nieto, Jose Camacho, Marı́a Jesús Monteseirı́n, Javier Conde, José Bedoya, Francisco J. Sobrino, Francisco |
| Abstract | Oxidizing agents are powerful activators of factors responsible for the transcriptional activation of cytokine-encoding genes involved in tissue injury. In this study we show evidence that STAT3 is a transcription factor whose activity is modulated by H2O2 in human lymphocytes, in which endogenous catalase had previously been inhibited. H2O2-induced nuclear translocation of STAT3 to form sequence-specific DNA-bound complexes was evidenced by immunoblotting of nuclear fractions and electrophoretic mobility shift assays, and vanadate was found to strongly synergize with H2O2. Moreover, anti-STAT3 antibodies specifically precipitated a protein of 92 kDa that becomes phosphorylated on tyrosine upon lymphocyte treatment with H2O2. Phenylarsine oxide, a tyrosine phosphatase inhibitor, and genistein, a tyrosine kinase inhibitor, cooperated and cancelled, respectively, the H2O2-promoted STAT3 nuclear translocation. Evidence is also presented, using Fe2+/Cu2+ions, that ⋅OH generated from H2O2through Fenton reactions could be a candidate oxygen reactive species to directly activate STAT3. Present data suggest that H2O2 and vanadate are likely to inhibit the activity of intracellular tyrosine phosphatase(s), leading to enhanced STAT3 tyrosine phosphorylation and hence its translocation to the nucleus. These results demonstrate that the DNA binding activity of STAT3 can be modulated by oxidizing agents and provide a framework to understand the effects of oxidative stress on the JAK-STAT signaling pathway. |
| Related Links | http://www.jbc.org/content/274/25/17580.abstract |
| Ending Page | 17586 |
| Starting Page | 17580 |
| Page Count | 7 |
| File Format | HTM / HTML PDF |
| ISSN | 00219258 |
| Journal | Journal of Biological Chemistry (JBC) |
| Issue Number | 25 |
| Volume Number | 274 |
| DOI | 10.1074/jbc.274.25.17580 |
| e-ISSN | 1083351X |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 1999-06-18 |
| Access Restriction | Open |
| Subject Keyword | Reactive oxygen intermediates (ROI) Phenylarsine oxide (PAO) Janus kinase (JAK) Protein-tyrosine kinases (PTK) Protein-tyrosine phosphatases (PTPase) Phenylmethylsulfonyl fluoride (PMSF) Phytohemagglutinin (PHA) Peripheral blood lymphocytes (PBL) Polyacrylamide gel electrophoresis (PAGE) Sis-inducible element (SIE) CELL BIOLOGY AND METABOLISM |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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