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.
Linder
B
B
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Harris
S
S
Eisen
A
A
Nissley
P
P
D002462:Cell Membrane / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis*; D004075:Diglycerides / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D007457:Iodine Radioisotopes; D012516:Osteosarcoma / Q000378:metabolism*; D037342:Pertussis Toxin; D017526:Receptor, IGF Type 1 / Q000502:physiology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
C011439:1,2-diacylglycerol; D004075:Diglycerides; D007457:Iodine Radioisotopes; D010566:Virulence Factors, Bordetella; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D004247:DNA; D037342:Pertussis Toxin; D017526:Receptor, IGF Type 1; D019204:GTP-Binding Proteins