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Originally published In Press as doi:10.1074/jbc.M301292200 on May 30, 2003

J. Biol. Chem., Vol. 278, Issue 32, 29667-29675, August 8, 2003
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Catalase Activity Is Regulated by c-Abl and Arg in the Oxidative Stress Response*

Cheng Cao {ddagger} §, Yumei Leng {ddagger} and Donald Kufe {ddagger} ¶

From the {ddagger}Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115 and the §Beijing Institute of Biotechnology, Beijing 100850, People's Republic of China

The Abl family of mammalian non-receptor tyrosine kinases includes c-Abl and Arg. Recent studies have demonstrated that c-Abl and Arg are activated in the response of cells to oxidative stress. This work demonstrates that catalase, a major effector of the cellular defense against H2O2, interacts with c-Abl and Arg. The results show that H2O2 induced binding of c-Abl and Arg to catalase. The SH3 domains of c-Abl and Arg bound directly to catalase at a P293FNP site. c-Abl and Arg phosphorylated catalase at Tyr231 and Tyr386 in vitro and in the response of cells to H2O2. The functional significance of the interaction is supported by the demonstration that cells deficient in both c-Abl and Arg exhibit substantial increases in H2O2 levels. In addition, c-abl/ arg/ cells exhibited a marked increase in H2O2-induced apoptosis compared with that found in the absence of either kinase. These findings indicate that c-Abl and Arg regulate catalase and that this signaling pathway is of importance to apoptosis in the oxidative stress response.


Received for publication, February 5, 2003 , and in revised form, May 29, 2003.

* This work was supported by NCI Grants CA42802 and CA49639 from the National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dana-Farber Cancer Inst., Harvard Medical School, Boston, MA 02115. Tel.: 617-632-3141; Fax: 617-632-2934; E-mail: donald_kufe{at}dfci.harvard.edu.


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