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J Biol Chem. 2001 Apr 13;276(15):11465-8. Epub 2001 Feb 23.

The ARG tyrosine kinase interacts with Siva-1 in the apoptotic response to oxidative stress.

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Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

Erratum in

  • J Biol Chem. 2012 Oct 19;287(43):36527. Koleske, A [corrected to Koleske, A J].


The Abl family of mammalian nonreceptor tyrosine kinases consists of c-Abl and ARG (Abl-related gene). Certain insights are available regarding the involvement c-Abl in the response of cells to stress. ARG, however, has no known function in cell signaling. The present studies demonstrate that ARG associates with the proapoptotic Siva-1 protein. The functional significance of the ARG-Siva-1 interaction is supported by the finding that ARG is activated by oxidative stress and that this response involves ARG-mediated phosphorylation of Siva-1 on Tyr(48). The proapoptotic effects of Siva-1 are accentuated in cells stably expressing ARG and are inhibited in ARG-deficient cells. Moreover, the proapoptotic effects of Siva-1 are abrogated by mutation of the Tyr(48) site. We also show that the apoptotic response to oxidative stress is attenuated in ARG-deficient cells and that this defect is corrected by reconstituting ARG expression. These findings support a model in which the activation of ARG by oxidative stress induces apoptosis by a Siva-1-dependent mechanism.

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