title: Glutathione peroxidase 1 is regulated by the c-Abl and Arg tyrosine kinases.
abstract: The c-Abl and Arg tyrosine kinases are activated in the cellular response to oxidative stress. The present studies demonstrate that c-Abl and Arg associate with glutathione peroxidase 1 (GPx1) and that this interaction is regulated by intracellular oxidant levels. The c-Abl and Arg SH3 domains bind directly to a proline-rich site in GPx1 at amino acids 132-145. GPx1 also functions as a substrate for c-Abl- and Arg-mediated phosphorylation on Tyr-96. The results further show that c-Abl and Arg stimulate GPx activity and that these kinases contribute to GPx-mediated protection of cells against oxidative stress. Our findings provide the first evidence that GPx1 is regulated by a signaling pathway that is activated in the oxidative stress response.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cao
authors.forename: Yumei
authors.initials: Y
authors.lastname: Leng
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.forename: Donald
authors.initials: D
authors.lastname: Kufe
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D004789:Enzyme Activation; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D018384:Oxidative Stress; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D018909:src Homology Domains; D000094765:Glutathione Peroxidase GPX1
chemical_list: D011994:Recombinant Proteins; D005979:Glutathione Peroxidase; C426236:ARG tyrosine kinase; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl; D005978:Glutathione; D000094765:Glutathione Peroxidase GPX1