title: Ubiquitination and degradation of the Arg tyrosine kinase is regulated by oxidative stress.
abstract: The c-Abl and Arg nonreceptor tyrosine kinases are activated in the response of cells to oxidative stress. The present studies demonstrate that treatment of cells with 0.1 mM H2O2 is associated with increased tyrosine phosphorylation of Arg and little effect on Arg levels. By contrast, exposure to 1.0 mM H2O2 decreased Arg phosphorylation. Treatment with 1.0 mM H2O2 was also associated with ubiquitination and degradation of Arg. The results show that Arg is stabilized in response to 0.1 mM H2O2 by autophosphorylation of Y-261, consistent with involvement of the Arg kinase function in regulating Arg levels. The results further demonstrate that c-Abl-mediated phosphorylation of Arg on Y-261 similarly confers Arg stabilization. In concert with these results, phosphorylation of Arg on Y-261 blocked H2O2-induced ubiquitination and thereby Arg degradation and inactivation. These findings demonstrate that Arg phosphorylation and degradation are differentially regulated by the degree of oxidative stress, and that Arg stability is conferred by phosphorylation of Y-261.
authors.affiliation: Beijing Institute of Biotechnology, Beijing 100850, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cao
authors.forename: Yanping
authors.initials: Y
authors.lastname: Li
authors.forename: Yumei
authors.initials: Y
authors.lastname: Leng
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Ma
authors.forename: Donald
authors.initials: D
authors.lastname: Kufe
mesh_terms: D001120:Arginine / Q000378:metabolism*; D001943:Breast Neoplasms / Q000473:pathology; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014452:Ubiquitins / Q000737:chemistry
chemical_list: D016877:Oxidants; D014452:Ubiquitins; D001120:Arginine; D006861:Hydrogen Peroxide; C426236:ARG tyrosine kinase; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl