Role of Src kinases and Syk in Fcgamma receptor-mediated phagocytosis and phagosome-lysosome fusion.
Phagocytosis is increased by Fcgamma receptors (FcgammaRs), and studies with syk(-/-) macrophages demonstrated that Syk kinase is required for FcgammaR phagocytosis. Similar studies with macrophages lacking the Src family kinases Hck, Fgr, and Lyn showed that these kinases are not required for phagocytosis but that they enhance the rate of particle engulfment. In this report we show that both wild-type and hck(-/-)fgr(-/-) macrophages expressed Fyn, Src, and Yes and that these kinases were activated on ingestion of immunoglobulin G (IgG)-coated particles and redistributed, together with Syk, to actin-rich phagocytic cups and the phagosomal membrane. At doses blocking IgG-dependent phagocytosis, the tyrosine kinase inhibitors PP1 and piceatannol inhibited both Src family kinase and Syk activities, as well as their redistribution to actin-rich phagocytic cups. Hck, Fgr, and Lyn were dispensable for lysosome-phagosome fusion (PLF) induced by IgG-coated particles. However, PP1 or piceatannol hampered unopsonized yeast-induced PLF despite the fact that they did not block yeast internalization.
Majeed
M
M
Department of Pathology, Section of General Pathology, University of Verona, Verona, Italy. meyma@ihm.liu.se
Caveggion
E
E
Lowell
C A
CA
Berton
G
G
D000199:Actins / Q000032:analysis; D000818:Animals; D001704:Biopolymers; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007074:Immunoglobulin G / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D008247:Lysosomes / Q000502:physiology*; D008561:Membrane Fusion / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008863:Microspheres; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis; D010588:Phagosomes / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051076:Proto-Oncogene Proteins c-fyn; D051572:Proto-Oncogene Proteins c-hck; D051575:Proto-Oncogene Proteins c-yes; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D017452:Receptors, IgG / Q000502:physiology*; D012441:Saccharomyces cerevisiae; D013267:Stilbenes / Q000494:pharmacology; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; D000199:Actins; D001704:Biopolymers; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D007074:Immunoglobulin G; D047908:Intracellular Signaling Peptides and Proteins; D009895:Opsonin Proteins; D011518:Proto-Oncogene Proteins; D011720:Pyrazoles; D011743:Pyrimidines; D017452:Receptors, IgG; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; C496632:Hck protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D051572:Proto-Oncogene Proteins c-hck; D051575:Proto-Oncogene Proteins c-yes; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C496639:Yes1 protein, mouse; C060902:lyn protein-tyrosine kinase; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases