title: Fc gamma RII activation induces cell surface ceramide production which participates in the assembly of the receptor signaling complex.
abstract: We studied an involvement of various cellular ceramide pools in signaling of immunoreceptor Fc gamma II (Fc gamma RII). The cell surface ceramide level was assessed by a technique based on binding of ceramide probes to intact cells. Total cellular ceramide was estimated by radioactive measurements. The activity of sphingomyelinases was measured by NBD-ceramide release while immunoprecipitation and immunoblotting were applied to analyze protein tyrosine phosphorylation. A complex pattern of protein phosphorylation was found to accompany Fc gamma RII activation and the phosphorylation was either diminished by imipramine or increased by B13, modulators of acid sphingomyelinase and acid ceramidase activity. The effects of the drugs on the phosphorylation of Fc gamma RII and NTAL were prominent and correlated with a reduction of the cell surface ceramide production by imipramine and an augmentation of the ceramide generation by B13. The ceramide generation followed activation of acid sphingomyelinase and preceded that of neutral sphingomyelinase. The level of cell surface ceramide was additionally elevated by exogenous bacterial sphingomyelinase, but only at later stages of the receptor activation. The total mass of ceramide was diminished in the course of receptor activation pointing to an engagement of enzymes metabolizing ceramide. The data indicate that Fc gamma RII activates enzymes of the sphingomyelin cycle which affect various sphingomyelin/ceramide pools in a cell.
authors.affiliation: The Nencki Institute of Experimental Biology, Department of Cell Biology, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Korzeniowski
authors.forename: Abo Bakr Abdel
authors.initials: AB
authors.lastname: Shakor
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Makowska
authors.forename: Anna
authors.initials: A
authors.lastname: Drzewiecka
authors.forename: Alicja
authors.initials: A
authors.lastname: Bielawska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kwiatkowska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Sobota
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002518:Ceramides / Q000096:biosynthesis*; D004789:Enzyme Activation; D006801:Humans; D016253:Microscopy, Immunoelectron; D019000:Phosphotyrosine / Q000378:metabolism; D011433:Propranolol / Q000031:analogs & derivatives; D011485:Protein Binding; D017452:Receptors, IgG / Q000378:metabolism* / Q000648:ultrastructure; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism
chemical_list: D002518:Ceramides; D017452:Receptors, IgG; D019000:Phosphotyrosine; C026477:N-(S-methyl)mercaptoethylpropranolol; D011433:Propranolol; D013108:Sphingomyelin Phosphodiesterase