Activation of tyrosine kinase signal pathways by radiation and oxidative stress.
Most research on ionizing radiation, ultraviolet radiation, and H2O2 exposure has focused on the well-known ability of such agents to damage cellular components, particularly DNA. However, recent studies have shown that these events also act directly on components of tyrosine kinase signal transduction pathways, resulting in their activation. Cells use these types of pathways to transmit signals from surface receptors to the nucleus in response to a wide variety of stimuli, ranging from hormones and growth factors such as insulin, erythropoietin, and epidermal growth factor to antigen stimulation of lymphocytes. We propose that cellular responses to radiation and oxidative stress involve the active process of tyrosine kinase signal transduction, in addition to damage to DNA and other cellular components, leading to the activation of transcription factors and the subsequent induction of gene expression. The ability of radiation and oxidative stress to bypass control by normal ligands to act on receptors and their signal transduction pathways offers a new perspective on the ways in which organisms can respond to stress.
Schieven
G L
GL
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121, USA.
Ledbetter
J A
JA