title: Protein kinase C as a multi-targeted feedback inhibitor regulating the Ca2+ responses to chemotactic peptide stimulation in the murine macrophage cell line PU5-1.8.
abstract: The role of protein kinase C (PKC) in the signal transduction process when macrophage cells were stimulated by the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMLP) was investigated in the cell line PU5-1.8. Addition of fMLP to PU5-1.8 cells induced a rapid generation of inositol trisphosphate and a translocation of PKC. Concomitantly there was an influx of Ca2+ followed by its expulsion. PKC was likely involved in Ca2+ extrusion as short-term pretreatment of cells with phorbol 12-myristate 13-acetate (PMA) enhanced the removal of preloaded 45Ca2+ but had no significant effect on fMLP-stimulated 45Ca2+ influx. Depletion of cellular PKC activity through down-regulation or exposure of cells to PKC inhibitors also blocked the fMLP-stimulated 45Ca2+ efflux. Further experiments using PMA revealed that PKC also decreased vesicular Ca2+ and stimulated the catabolism of inositol 1,4,5-trisphosphate. These results lend support to the notion that PKC serves as a negative feedback modulator in Ca2+ signalling and further suggest that it operates at several target sites.
authors.affiliation: Department of Biochemistry, Chinese University of Hong Kong, Shatin, NT.
authors.forename: S K
authors.initials: SK
authors.lastname: Kong
authors.forename: Y M
authors.initials: YM
authors.lastname: Choy
authors.forename: C Y
authors.initials: CY
authors.lastname: Lee
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005246:Feedback; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D009240:N-Formylmethionine Leucyl-Phenylalanine; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium