title: Topological regulation of cell-membrane phosphoinositidase C.
abstract: Although the translocation of protein kinase C and phospholipase A2 are well documented, no information is available about the possible down-modulation of transmembrane phospholipase C. We found that TPA induced a dose-dependent (10-200 nM) and time-dependent (15 min-6 h) down-modulation of transmembrane phosphoinositidase C (PLC-PI) on lymphoid cells (CEM-CM3 and WIL2-NS) and epitheloid carcinoma cells (HeLa S3) but not on human fibroblasts (MRC-5). Cell-surface expression of PLC-PI on intact cells was assayed by flow cytometry using saturating concentrations of polyclonal anti-PLC-PI antibodies and phycoerythrin-conjugate. A control phorbol-ester which does not activate protein kinase C (PKC) had no internalization effect on PLC-PI. PKC inhibitors staurosporine (2.5 nM) and H-7 (10 microM) partially inhibited the TPA effect. Cytochalasin B (40 micrograms/ml) did not modify the TPA-induced PLC-PI down-modulation. The effect of TPA on PLC-PI seems quite specific since no internalization was induced by TPA on transmembrane phosphatidylcholine-preferring PLC expression. These results show that TPA can translocate the membrane-bound PLC-PI, probably by PKC activation.
authors.affiliation: Nicolau Institute of Virology, Bucharest, Romania.
authors.forename: S N
authors.initials: SN
authors.lastname: Constantinescu
authors.forename: L M
authors.initials: LM
authors.lastname: Popescu
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D003571:Cytochalasin B / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000096:biosynthesis / Q000378:metabolism*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D003571:Cytochalasin B; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate