title: Examination of the role of the proteolytically-activated form of protein kinase C in the differentiation of human haemopoietic cells.
abstract: In neutrophils, the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induced the translocation of the Ca(++)- and phospholipid-dependent protein kinase, protein kinase C (PK-C) from the soluble to the particulate fraction. At the same time there was a corresponding increase in the amount of Ca(++)- and phospholipid-independent protein kinase activity recovered in the soluble fraction. This soluble Ca(++)- and phospholipid-independent protein kinase presumably reflects proteolytic activation of the particulate associated PK-C. Bone marrow and undifferentiated HL-60 cells also translocated PK-C to the particulate fraction in response to TPA but did not accumulate the soluble Ca(++)- and phospholipid-independent form of the enzyme. Similar results were obtained using HL-60 cells induced to differentiate with dimethyl sulphoxide (DMSO), recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) or 1 alpha,25-dihydroxyvitamin D3. There was also no significant change in either the number or time of expression of differentiation-specific cell surface antigens observed on HL-60 cells induced to differentiate with either DMSO, 1 alpha,25-dihydroxyvitamin D3 or TPA in the presence of cyclosporin A, an agent reported to inhibit the proteolytic breakdown of PK-C to the Ca(++)- and phospholipid-independent form. Likewise, cyclosporin A did not affect the rate of extent of differentiation of primary bone marrow cell cultures. These results suggest that the proteolytically activated and phospholipid-independent form of PK-C is probably not involved in haemopoietic cell differentiation.
authors.affiliation: School of Biological Sciences, Flinders University of South Australia, Adelaide.
authors.forename: S J
authors.initials: SJ
authors.lastname: Hardy
authors.forename: D N
authors.initials: DN
authors.lastname: Haylock
authors.forename: A F
authors.initials: AF
authors.lastname: Lopez
authors.forename: A W
authors.initials: AW
authors.lastname: Murray
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects / Q000502:physiology; D001854:Bone Marrow Cells; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000493:pharmacokinetics / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010447:Peptide Hydrolases / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016572:Cyclosporine; D011493:Protein Kinase C; D010447:Peptide Hydrolases; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D004121:Dimethyl Sulfoxide