Abstract
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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Feller, S. M., Knudsen, B. & Hanafusa, H. EMBO J. 13, 2341–2351 (1994).
Ren, R., Ye, Z.-S. & Baltimore, D. Genes Dev. 8, 783–795 (1994).
Songyang, Z. et al. Nature 373, 536–539 (1995).
Sherman, S. E. & Lippard, S. J. Chem. Rev. 87, 1153–1181 (1987).
Tomasz, M., Chawla, A. K. & Lipman, R. Biochemistry 27, 3182–3187 (1988).
Pulverer, B. J., Kyriakis, J. M., Avruch, J., Nikolakaki, E. & Woodgett, J. R. Nature 353, 670–674 (1991).
Kyriakis, J. M. et al. Nature 369, 156–160 (1994).
Derijard, B. et al. Cell 76, 1025–1037 (1994).
Engelberg, D., Klein, C., Martinetto, H., Struhl, K. & Karin, M. Cell 77, 381–390 (1994).
Tybulewicz, V. L. J., Crawford, C. E., Jackson, P., Bronson, R. T. & Mulligan, R. C. Cell 65, 1153–1163 (1991).
Welch, P. J. & Wang, J. Y. Cell 75, 779–790 (1993).
Sawyers, C. L., McLaughlin, J., Goga, A., Havillk, M. & Witte, O. Cell 77, 121–131 (1994).
Mattioni, T., Jackson, P. K., van Huijsduijnen, O. B.-H. & Picard, D. Oncogene 10, 1325–1333 (1995).
Kipreos, E. T. & Wang, J. Y. J. Science 248, 217–220 (1990).
Kipreos, E. T. & Wang, J. Y. J. Science 256, 382–385 (1992).
Feller, S. M., Ren, R., Hanafusa, H. & Baltimore, D. Trends biochem. Sci. 19, 453–458 (1994).
Saleem, A., Yuan, Z. M., Kufe, D. W. & Kharbanda, S. J. Immun. 154, 4150–4156 (1995).
Morgenstern, J. P. & Land, H. Nucleic Acids Res. 18, 3587–3596 (1990).
Pear, W. S., Nolan, G. P., Scott, M. L. & Baltimore, D. Proc. natn. Acad. Sci. U.S.A. 90, 8392–8396 (1993).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kharbanda, S., Ren, R., Pandey, P. et al. Activation of the c-Abl tyrosine kinase in the stress response to DMA-damaging agents. Nature 376, 785–788 (1995). https://doi.org/10.1038/376785a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/376785a0
This article is cited by
-
ABL1 kinase as a tumor suppressor in AML1-ETO and NUP98-PMX1 leukemias
Blood Cancer Journal (2023)
-
Anti-apoptotic HAX-1 suppresses cell apoptosis by promoting c-Abl kinase-involved ROS clearance
Cell Death & Disease (2022)
-
Enhanced pro-apoptosis gene signature following the activation of TAp63α in oocytes upon γ irradiation
Cell Death & Disease (2022)
-
MicroRNA-203 suppresses proliferation in liver cancer associated with PIK3CA, p38 MAPK, c-Jun, and GSK3 signaling
Molecular and Cellular Biochemistry (2018)
-
GADD45α modulates curcumin sensitivity through c-Abl- and JNK-dependent signaling pathways in a mismatch repair-dependent manner
Molecular and Cellular Biochemistry (2016)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.