Mitogenicity and transforming activity of the insulin-like growth factor-I receptor with mutations in the tyrosine kinase domain.

摘要: We have investigated the effect of mutations in tyrosines 1131, 1135, and 1136 human insulin-like growth factor-I receptor (IGF-IR) on transformation mammalian cells. used for this purpose R- cells, which are 3T3-like fibroblasts derived from mouse embryos with a targeted disruption IGF-IR genes. These cells no IGF-IR, do not grow serum-free medium supplemented factors that sustain 3T3 cannot be transformed by simian virus 40 large tumor antigen or other oncogenes. The were transfected plasmids expressing: 1) wild type cDNA; 2) triple mutation above mentioned tyrosines; 3) receptors single tyrosine mutations. Cells expressing mutants Y1 (Y1131F) Y2 (Y1135F) grew solely IGF-I. mutant YF Y3 (Y1136F) failed to response IGF-I only. All mutants, though, form colonies soft agar, indicating fully functional is more critical anchorage-independent than monolayer growth. expression plasmid also functioned as dominant negative, inhibiting antigen.