Evidence against roles for pertussis toxin sensitive G proteins or diacylglycerol generation in insulin-like growth factor-1 stimulated DNA synthesis in MG-63 osteosarcoma cells.

A pertussis toxin-sensitive G protein has been reported to play a role in the mitogenic response to insulin-like growth factor-I (IGF-I) in mouse fibroblasts, and diacylglycerol generation has been shown to accompany growth stimulation by IGF-I of several cell lines. We have examined the roles of pertussis toxin sensitive G proteins and diacylglycerol generation in signaling by the insulin-like growth factor-I receptor in a cell line that is very responsive to IGF-I, the human osteosarcoma cell line, MG-63. Pertussis toxin failed to inhibit IGF-I induced [3H]-thymidine incorporation into DNA. Furthermore, the stable analog GTP gamma S had no effect on the binding of 125I-labelled IGF-I to MG-63 membrane preparations. Following addition of IGF-I to growth-arrested MG-63 cells there was no increase in diacylglycerol levels over 30 min. We conclude that the activated IGF-I receptor does not use pertussis toxin sensitive G proteins or diacylglycerol generation in a pathway leading to DNA synthesis in MG-63 cells.