Activation of the c-Abl tyrosine kinase in the stress response to DMA-damaging agents

• Published in: Nature (London) Vol. 376; no. 6543; pp. 785 - 788
• Main Authors: Kharbanda, Surender, Ren, Ruibao, Pandey, Pramod, Shafman, Timothy D, Feller, Stephen M, Weichselbaum, Ralph R, Kufe, Donald W
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 31-08-1995
• Subjects: Ionizing radiation
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/376785a0

THE product of the c-abl gene is a non-receptor tyrosine kinase that is localized to the nucleus and cytoplasm. The precise function of c-Abl is unknown. Here we show that ionizing radiation activates c-Abl. Similar results were obtained with the alkylating agents cis-platinum and mitomycin C. We also demonstrate that cells deficient in c-Abl fail to activate Jun kinase (JNK/SAP kinase) after ionizing radiation or alkylating agent exposure and that reconstitution of c-Abl in these cells restores that response. In contrast, the stress response to tumour-necrosis factor is stimulated by a c-Abl-independent mechanism. These findings indicate that c-abl is involved in the stress response to DNA-damaging agents.