title: Hydrogen peroxide inhibits activity of the IGF-1 receptor kinase.
abstract: IGF-1 receptor (IGF1R) is a transmembrane tyrosine kinase, which is indispensable for cellular growth and differentiation. Using a recombinant GST-tagged cytosolic fragment of IGF1R (GST-IGFK), we now show that oxidation by low doses (50 muM) of hydrogen peroxide markedly inhibits maximum phosphate incorporation in autophosphorylation and substrate phosphorylation assays. A similar inhibition was observed on the activity of intact IGF1R after treatment of T-47D cells. These results are in sharp contrast to the positive influence of hydrogen peroxide on the highly homologous insulin receptor kinase, which was assayed for comparison. This reciprocal influence of physiologically relevant doses of hydrogen peroxide may have important implications on signal transduction of the closely related receptors for insulin and IGF-1.
authors.affiliation: Division of Immunochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany. T.Schmitt@dkfz.de
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Schmitt
authors.forename: Helmut
authors.initials: H
authors.lastname: Klein
authors.forename: Wulf
authors.initials: W
authors.lastname: Dröge
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry; D049109:Cell Proliferation; D005982:Glutathione Transferase / Q000737:chemistry*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007700:Kinetics; D050356:Lipid Metabolism; D018384:Oxidative Stress; D010710:Phosphates / Q000737:chemistry; D010766:Phosphorylation; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015398:Signal Transduction
chemical_list: D010710:Phosphates; D000244:Adenosine Diphosphate; D006861:Hydrogen Peroxide; D005982:Glutathione Transferase; D017526:Receptor, IGF Type 1