Peroxynitrite signaling: receptor tyrosine kinases and activation of stress-responsive pathways |
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Authors: | Klotz Lars-Oliver Schroeder Peter Sies Helmut |
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Affiliation: | Institut für Physiologische Chemie I, Heinrich-Heine-Universit?t Düsseldorf, Düsseldorf, Germany. larsoliver.klotz@uni-duesseldorf.de |
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Abstract: | Peroxynitrite, generated for example in inflammatory processes, is capable of nitrating and oxidizing biomolecules, implying a considerable impact on the integrity of cellular structures. Cells respond to stressful conditions by the activation of signaling pathways, including receptor tyrosine kinase-dependent pathways such as mitogen-activated protein kinases and the phosphoinositide-3-kinase/Akt pathway. Peroxynitrite affects signaling pathways by nitration as well as by oxidation: while nitration of tyrosine residues by peroxynitrite modulates signaling processes relying on tyrosine phosphorylation and dephosphorylation, oxidation of phosphotyrosine phosphatases may lead to an alteration in the tyrosine phosphorylation/dephosphorylation balance. The flavanol (-)-epicatechin is a potent inhibitor of tyrosine nitration and may be employed as a tool to distinguish signaling effects due to tyrosine nitration from those that are due to oxidation reactions. |
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