EVIDENCE AGAINST ROLES FOR PERTUSSIS-TOXIN-SENSITIVE C-PROTEINS OR DIACYLGLYCEROL GENERATION IN INSULIN-LIKE GROWTH-FACTOR-I 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 diacyglycerol generation has been shown to acco mpany growth stimulation by IGF-I of several cell lines. We have exami ned the roles of pertussis toxin sensitive G proteins and diacylglycer ol generation in signaling by the insulin-like growth factor-I recepto r in a cell line that is very responsive to IGF-I, the human osteosarc oma cell line, MG-63. Pertussis toxin failed to inhibit IGF-I induced [H-3]-thymidine incorporation into DNA. Furthermore, the stable analog GTP gamma S had no effect on the binding of I-125-labelled IGF-I to M G-63 membrane preparations. Following addition of IGF-I to growth-arre sted MG-63 cells there was no increase in diacylglycerol levels over 3 0 min. We conclude that the activated IGF-I receptor does not use pert ussis toxin sensitive G proteins or diacylglycerol generation in a pat hway leading to DNA synthesis in MG-63 cells.