12/15-lipoxygenase–derived lipid peroxides control receptor tyrosine kinase signaling through oxidation of protein tyrosine phosphatases
| Autor: | Heidi Förster, Rob Hooft van Huijsduijnen, Arne Östman, Pontus Aspenström, Åsa Sandin, Frank Böhmer, Alexander Seiler, Georg W. Bornkamm, Jeroen Frijhoff, Marcus Conrad, Olof Rådmark, Markus Dagnell |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Lipid Peroxides
metabolism [Protein Tyrosine Phosphatases] genetics [Glutathione Peroxidase] Protein tyrosine phosphatase Arachidonate 12-Lipoxygenase GPX4 Receptor tyrosine kinase Receptor Platelet-Derived Growth Factor beta Mice Animals Arachidonate 15-Lipoxygenase metabolism [Reactive Oxygen Species] 12-15-lipoxygenase Phosphorylation chemistry.chemical_classification Glutathione Peroxidase Reactive oxygen species Multidisciplinary biology Lipid peroxide Receptor Protein-Tyrosine Kinases metabolism [Receptor Protein-Tyrosine Kinases] metabolism [Arachidonate 12-Lipoxygenase] metabolism [Lipid Peroxides] Biological Sciences Phospholipid Hydroperoxide Glutathione Peroxidase metabolism [Receptor Platelet-Derived Growth Factor beta] Cell biology Enzyme Activation metabolism [Glutathione Peroxidase] enzymes and coenzymes (carbohydrates) Biochemistry chemistry biology.protein metabolism [Arachidonate 15-Lipoxygenase] ddc:500 Protein Tyrosine Phosphatases Signal transduction Reactive Oxygen Species Oxidation-Reduction Platelet-derived growth factor receptor Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America 107(36), 15774-15779 (2010). doi:10.1073/pnas.1007909107 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1007909107 |
| Popis: | Protein tyrosine phosphatases (PTPs) are regulated through reversible oxidation of the active-site cysteine. Previous studies have implied soluble reactive oxygen species (ROS), like H 2 O 2 , as the mediators of PTP oxidation. The potential role(s) of peroxidized lipids in PTP oxidation have not been described. This study demonstrates that increases in cellular lipid peroxides, induced by disruption of glutathione peroxidase 4, induce cellular PTP oxidation and reduce the activity of PDGF receptor targeting PTPs. These effects were accompanied by site-selective increased PDGF β-receptor phosphorylation, sensitive to 12/15-lipoxygenase (12/15-LOX) inhibitors, and increased PDGF-induced cytoskeletal rearrangements. Importantly, the 12/15-LOX–derived 15-OOH-eicosatetraenoic acid lipid peroxide was much more effective than H 2 O 2 in induction of in vitro PTP oxidation. Our study thus establishes that lipid peroxides are previously unrecognized inducers of oxidation of PTPs. This identifies a pathway for control of receptor tyrosine kinase signaling, which might also be involved in the etiology of diseases associated with increased lipid peroxidation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|