Abstract
Available evidence suggests that insulin-like growth factor I receptor (IGF-IR) expression leads to increased cellular radioresistance via downstream survival signals. However, expression of a membrane-targeted C-terminal fragment of IGF-IR has been reported to send a signal strongly and ultimately lead to cell death; this pro-death signal is not suppressed by survival signals from IGF-IR. We sought to explore the ability of the C-terminus of intact IGF-IR to become activated and lead to the abrogation of IGF-IR-mediated radioresistance. In the present study, we show evidence that IGF-IR-mediated radioresistance could be abrogated by mutations at tyrosine residues 1250 and 1251 in the C-terminus. This effect is presumably through activation of the C-terminal cell killing effect in IGF-IR because the essential domain for the effect was also required for the abrogation of radioresistance and the activation of downstream survival signaling pathways are still maintained. [J Radiat Res 44:422 (2003)]
