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 [3H]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.
Choudhury
G G
GG
Department of Cellular Biology, University of Texas Health Science Center, San Antonio 78284-7762.
Sylvia
V L
VL
Sakaguchi
A Y
AY
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004171:Diploidy; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects*; D010738:Type C Phospholipases / Q000494:pharmacology*
D010738:Type C Phospholipases