Abstract
Raf-1 protein serine/threonine kinase has been implicated in growth and damage-responsive signal transduction pathways. Several reports indicate an important role of Ras protein in the growth factor-induced activation of Raf-1. Here we investigated the possible involvement of Ras in ionizing radiation-induced activation of Raf-1. Irradiation of MDA-MB 231 human breast cancer cells caused an increase in GTP-binding and hydrolysis on Ras, and co-immunoprecipitations of endogenous Grb2 with Sos and Raf-1 with Ras. An increase in the level of membrane-bound Raf-1, and tyrosine-phosphorylation of Raf-1 were observed after irradiation. Consistent with these changes, irradiation of cells stimulated the catalytic activity of Raf-1. Finally, radiation treatment of breast cancer cells led to an increase in the phosphorylation and activity of the mitogen-activated protein kinase. Based on these biochemical modifications in vivo, we conclude that Raf-1 functions as an effector of Ras in the radiation-responsive signal transduction pathway leading to the activities of Raf-1 and mitogen-activated protein kinase.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Suy, S., Anderson, W., Dent, P. et al. Association of Grb2 with Sos and Ras with Raf-1 upon gamma irradiation of breast cancer cells. Oncogene 15, 53–61 (1997). https://doi.org/10.1038/sj.onc.1201165
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201165
Keywords
This article is cited by
-
RAF antisense oligonucleotide as a tumor radiosensitizer
Oncogene (2003)
-
MAPK pathways in radiation responses
Oncogene (2003)
-
Ionizing radiation modulates vascular endothelial growth factor (VEGF) expression through multiple mitogen activated protein kinase dependent pathways
Oncogene (2001)
-
Dominant negative EGFR-CD533 and inhibition of MAPK modify JNK1 activation and enhance radiation toxicity of human mammary carcinoma cells
Oncogene (1999)
-
The RAF family: an expanding network of post-translational controls and protein-protein interactions
Cell Research (1998)