PMID: 9657526Jul 10, 1998Paper

Redox priming of the insulin receptor beta-chain associated with altered tyrosine kinase activity and insulin responsiveness in the absence of tyrosine autophosphorylation

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
E SchmidW Dröge

Abstract

Induction of tyrosine kinase activity of the insulin receptor (IR) beta-chain is believed to require its autophosphorylation at Tyr1162, Tyr1163, and Tyr1158. However, the mechanism of the initial phosphorylation is poorly understood. We show that treatment of IR-transfected Chinese hamster ovary cells with antioxidants inhibits insulin responsiveness. Conversely, partial inhibition of glutathione biosynthesis by buthionine sulfoximine (BSO) and glutathione reductase by 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), i.e., procedures that intracellularly induce mildly oxidative conditions, caused a decrease in IR beta-chain sulfhydryl groups and enhanced synergistically the induction of IR tyrosine phosphorylation by insulin. The IR beta-chain from cells treated with BSO/BCNU in the absence of insulin was not detectably tyrosine phosphorylated, but nevertheless was functionally altered, as demonstrated in vitro by a moderate kinase activity at lowATP concentrations (5 nM) and a strong kinase activity at 25 microM ATP. This activity was found to be specific for tyrosine (not for serine or threonine), and tryptic peptide maps indicated that it is more selective than that induced by insulin. Moreover, the kinase activity from BSO/BC...Continue Reading

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Citations

Jan 5, 2002·Physiological Reviews·Wulf Dröge
Jan 22, 2005·Annals of the New York Academy of Sciences·S DominiciA Pompella
Apr 12, 2006·Current Opinion in Clinical Nutrition and Metabolic Care·Wulf Dröge
Nov 6, 2008·Diabetes·Claire RegazzettiSophie Giorgetti-Peraldi
Apr 25, 2018·CNS Neuroscience & Therapeutics·Igor PomytkinTatyana Strekalova
Sep 7, 2002·Antioxidants & Redox Signaling·Izumi NakashimaYoshiyuki Kawamoto
Jul 21, 2005·Free Radical Research·Paola Chiarugi
Dec 3, 2005·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Wulf Dröge
Jun 19, 2008·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Ana Maria Cuervo
Jan 16, 2009·Dynamic Medicine : DM·Kelsey Fisher-Wellman, Richard J Bloomer
Jul 16, 2010·Antioxidants & Redox Signaling·Peter L J de KeizerTobias B Dansen
May 7, 2011·Obesity·Amany K ElshorbagyHelga Refsum
Dec 13, 2005·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Wulf Dröge
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Aug 27, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·E SchmidW Dröge
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Aug 25, 2010·Pharmacology & Therapeutics·Gabriella LeonarduzziGiuseppe Poli

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