Protein kinase C-alpha participates in FcgammaR-mediated phagocytosis in macrophages.
Phagocytosis of IgG-opsonized particles by macrophages requires the activation of protein kinase C (PKC), a family of protein serine/threonine kinases. In the present study, we have investigated the role of the PKC-alpha isoenzyme in FcgammaR-mediated phagocytosis using clones of the mouse macrophage cell line RAW 264. 7 overexpressing a dominant-negative (DN) mutant of PKC-alpha. Overexpression of DN PKC-alpha had no effect on the attachment of IgG-opsonized sheep red blood cells, but inhibited their internalization. Further analysis of the signaling events induced by IgG-opsonized sheep red blood cells revealed that whereas tyrosine phosphorylation of Syk was normal, phosphorylation of ERK 1/2 (p42/44) was impaired in DN PKC-alpha-overexpressing macrophages. These observations suggest a role for PKC-alpha in the regulation of FcgammaR-induced phagocytosis and signal transduction.
Breton
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INRS-Institut Armand-Frappier, Laval, Québec, H7V 1B7, Canada.
Descoteaux
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D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D002478:Cells, Cultured; D004792:Enzyme Precursors / Q000378:metabolism; D004912:Erythrocytes / Q000502:physiology; D007074:Immunoglobulin G / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000096:biosynthesis / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000096:biosynthesis / Q000502:physiology*; D051571:Protein Kinase C-alpha; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017452:Receptors, IgG / Q000502:physiology*; D012756:Sheep; D000072377:Syk Kinase; D014443:Tyrosine / Q000378:metabolism
D015703:Antigens, CD; D004792:Enzyme Precursors; C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D017452:Receptors, IgG; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases