Ubiquitination and degradation of the Arg tyrosine kinase is regulated by oxidative stress.

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.Oncogene (2005) 24, 2433-2440. doi:10.1038/sj.onc.1208454 Published online 7 February 2005 [ABSTRACT FROM AUTHOR]