The ras Oncogene and Myogenic Commitment and Differentiation
When proliferating BC3H1 muscle cells are shifted to low serum conditions, they exit from the cell cycle and differentiate, activating a family of muscle-specific genes. Addition of the purified growth factors, fibroblast growth factor (FGF) or thrombin reverses this process and stimulates these cells to reenter the cell cycle. Pertussis toxin (PT) blocks thrombin’s, but not FGF’s, effects on muscle proliferation/differentiation. Thrombin, therefore, requires a G protein to transduce its signal. In addition, PT promoted differentiation in the presence of high concentrations of serum. Serum then contains a mitogen that signals through a PT-sensitive pathway in order to promote proliferation and inhibit muscle gene transcription. Transfection of the activated Ha-ras oncogene into BC3H1 and 10T1/2 cells blocked muscle differentiation in both of these lines. PT could not rescue the ras-mediated inhibition of differentiation. These results suggest that G protein-like molecules play important roles in transducing growth factor signals that control myogenesis.
KeywordsFibroblast Growth Factor Creatine Kinase Pertussis Toxin Creatine Kinase Activity Muscle Cell Line
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