Ubiquitination and degradation of the Arg tyrosine kinase is regulated by oxidative stress
Ubiquitination and degradation of the Arg tyrosine kinase is regulated by oxidative stress
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DOI：
10.1038/sj.onc.1208454
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发表时间：
2005-04-07
期刊：
影响因子：
8
通讯作者：
Kufe, D
中科院分区：
文献类型：
--
作者：
Cao, C;Li, YP;Kufe, D
C-Abl和Arg非受体酪氨酸激酶在细胞对氧化应激的反应中被激活。目前的研究表明，0.1 mM H_2O_2处理细胞与增加Arg的酪氨酸磷酸化有关，而对Arg水平几乎没有影响。相比之下，暴露于1.0 mM H_2O_2可降低Arg的磷酸化水平。1.0 mM H_2O_2处理也与Arg的泛素化和降解有关。结果表明，精氨酸对0.1 mM H_2O_2的反应是通过Y-261的自动磷酸化来稳定的，这与Arg激酶功能参与调节Arg水平是一致的。结果进一步证明，c-Abl介导的精氨酸在Y-261上的磷酸化类似地提供了Arg的稳定性。与这些结果一致的是，精氨酸在Y-261上的磷酸化阻止了过氧化氢诱导的泛素化，从而阻止了精氨酸的降解和失活。这些发现表明，精氨酸的磷酸化和降解受氧化应激程度的不同调节，精氨酸的稳定性是通过Y-261的磷酸化来实现的。
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 0.1mM H2O2 is associated with increased tyrosine phosphorylation of Arg and little effect on Arg levels. By contrast, exposure to 1.0mM H2O2 decreased Arg phosphorylation. Treatment with 1.0mM H2O2 was also associated with ubiquitination and degradation of Arg. The results show that Arg is stabilized in response to 0.1mM 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.