Density-dependent inhibition of cell growth is correlated with the activity of a cell surface phosphatidylinositol-specific phospholipase C.
We previously identified a novel phospatidylinositol-specific phospholipase C (PI-PLC) present at the surface of Swiss 3T3 cells using a fluorescent analog of PI and showed that this cell surface PI-PLC (csPI-PLC) activity increases with increasing cell density (J. Biol. Chem. 265, 5337-5340 (1990)). Here, we find that csPI-PLC activity also increased in cultures in which growth was inhibited due to serum deprivation. csPI-PLC was inhibited by agents that inhibit other mammalian PI-PLCs, but not by treatments which inhibit glycosyl PI-PLCs (GPI-PLCs). We also extended our studies using fluorescent PI to other cell types and found that csPI-PLC activity was present only in cell lines that exhibit growth inhibition upon reaching confluency (Swiss 3T3, 3T3-L1, BALB/c 3T3, and normal rat kidney (NRK) fibroblasts), but not in cell lines that are tumorigenic and/or do not exhibit growth inhibition in a density-dependent manner (Chinese hamster ovary (CHO), mouse L, SV-40 transformed BALB/c 3T3 (SV-T2), baby hamster kidney (BHK), and Chinese hamster lung (V79) fibroblasts). These results support the hypothesis that csPI-PLC plays a role in the density-dependent inhibition of cell growth.
Ting
A E
AE
Department of Embryology, Carnegie Institution of Washington, Baltimore, MD 21210.
Pagano
R E
RE
D016475:3T3 Cells / Q000378:metabolism*; D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D010716:Phosphatidylinositols / Q000378:metabolism*; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000187:drug effects / Q000378:metabolism*
D016895:Culture Media, Serum-Free; D005456:Fluorescent Dyes; D008081:Liposomes; D010716:Phosphatidylinositols; C063510:1,2-(oleoyl)-N-(6-((7-nitrobenz-2-oxa-1,3-diazo-4-yl)aminocaproyl))phosphatidylinositol; D010738:Type C Phospholipases; D009327:4-Chloro-7-nitrobenzofurazan