title: Potentiation of Gi-mediated phospholipase C activation by retinoic acid in HL-60 cells. Possible role of G gamma 2.
abstract: Differentiated HL-60 cells acquire responsiveness to fMet-Leu-Phe (fMLP), which activates phospholipase C and O2- generation in a pertussis toxin-sensitive manner. Addition of retinoic acid (RA) for the last 24 h during dimethyl sulfoxide (Me2SO)-induced differentiation enhanced fMLP-dependent signals and interaction between fMLP receptor and G(i). RA modifies both the function and subunit composition of G(i)2, the predominant G(i) of HL-60 membranes, as shown by comparing purified G(i)2 from membranes of Me2SO-treated cells (D-G(i)2) to G(i)2 from membranes of cells treated with both Me2SO and RA (DR-G(i)2). As compared to D-G(i)2, DR-G(i)2 induced more fMLP binding when added to membranes of pertussis toxin-treated HL-60 cells and, in the presence of GTP gamma S, stimulated beta gamma-sensitive phospholipase C in extracts of HL-60 cells to a much greater extent at a lower concentrations. Immunoblasts revealed that RA induced expression of the gamma 2 subunit, which was otherwise undetectable in G(i)2 purified from HL-60 cells or in HL-60 membranes. Possibly by inducing expression of gamma 2, RA alters two functions of the G(i) beta gamma subunit, modulation of fMLP receptor-G(i)2 coupling and activation of the effector, Phospholipase C.
authors.affiliation: Department of Pharmacology, University of California, San Francisco 94143.
authors.forename: T
authors.initials: T
authors.lastname: Iiri
authors.forename: Y
authors.initials: Y
authors.lastname: Homma
authors.forename: Y
authors.initials: Y
authors.lastname: Ohoka
authors.forename: J D
authors.initials: JD
authors.lastname: Robishaw
authors.forename: T
authors.initials: T
authors.lastname: Katada
authors.forename: H R
authors.initials: HR
authors.lastname: Bourne
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002846:Chromatography, Affinity; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D015870:Gene Expression; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D046911:Macromolecular Substances; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D046911:Macromolecular Substances; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D014212:Tretinoin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006160:Guanosine Triphosphate; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D004121:Dimethyl Sulfoxide