Redundancy of radioresistant signaling pathways originating from insulin-like growth factor I receptor.

摘要: The insulin-like growth factor I receptor (IGF-IR) has the ability to confer clonogenic radioresistance following ionizing irradiation. We attempted determine downstream pathways involved in IGF-IR-mediated and used mouse embryo fibroblasts deficient endogenous IGF-IR (R−) as recipients for a number of mutant IGF-IRs. Mutational analysis revealed that tyrosine at residue 950 (Tyr-950) IGF-IR, well C-terminal domain, are required both domains must be mutated abrogate phenotype. Furthermore, contribution was analyzed by combining use wild-type or Tyr-950 mutants with specific inhibitors phosphatidylinositol 3′-kinase (PI3-K) mitogen-activated protein extracellular signal-regulated kinase (ERK) (MEK). Radioresistance could induced long stimulate MEK/ERK pathway retained. This confirmed expression constitutively active MEK R− cells. PI3-K alone not sufficient, but activation coupled pathway-independent signals from C terminus able induce radioresistance. Taken together, these results indicate radioresistant signaling mechanism progresses through redundant pathways.