DECLINE OF SIGNAL TRANSDUCTION BY PHOSPHOLIPASE C-GAMMA-1 IN IMR-90 HUMAN-DIPLOID FIBROBLASTS AT HIGH POPULATION DOUBLING LEVELS

During cellular senescence in vitro, the cells do not respond mitogenically to serum growth factors at high population doubling levels. Phospholipase C activity in low PDL IMR 90 cells showed a 4.7-fold stimulation in response to 10% serum compared to 3.3-fold in high PDL cells when measured in whole cell extracts. Immunoaffinity purified tyrosine phosphorylated protein fraction showed a greater increase (5.2-fold) in phospholipase C activity in low PDL than high PDL cells (2.1-fold) in response to serum. Serum stimulated PLC-gamma-1 activity was diminished in high PDL cells. Immunokinase assay of PLC-gamma-1 immunoprecipitates from serum stimulated IMR 90 fibroblasts suggested that diminished enzymatic activity in high PDL cells is not due to less receptor coupled tyrosine phosphorylated PLC-gamma-1 enzyme. Serum stimulated [H-3]thymidine incorporation into DNA declined in parallel with the activity of PLC-gamma-1, suggesting that its activation might play significant roles in this in vitro model for cellular senescence.