PMID- 11698501 OWN - NLM STAT- MEDLINE DCOM- 20011207 LR - 20161124 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 70 IP - 5 DP - 2001 Nov TI - Role of Src kinases and Syk in Fcgamma receptor-mediated phagocytosis and phagosome-lysosome fusion. PG - 801-11 AB - 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. FAU - Majeed, M AU - Majeed M AD - Department of Pathology, Section of General Pathology, University of Verona, Verona, Italy. meyma@ihm.liu.se FAU - Caveggion, E AU - Caveggion E FAU - Lowell, C A AU - Lowell CA FAU - Berton, G AU - Berton G LA - eng GR - DK50267/DK/NIDDK NIH HHS/United States GR - HL54476/HL/NHLBI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine) RN - 0 (Actins) RN - 0 (Biopolymers) RN - 0 (Enzyme Inhibitors) RN - 0 (Enzyme Precursors) RN - 0 (Immunoglobulin G) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Opsonin Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Pyrazoles) RN - 0 (Pyrimidines) RN - 0 (Receptors, IgG) RN - 0 (Stilbenes) RN - 6KS3LS0D4F (3,3',4,5'-tetrahydroxystilbene) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.2 (Fyn protein, mouse) RN - EC 2.7.10.2 (Hck protein, mouse) RN - EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn) RN - EC 2.7.10.2 (Proto-Oncogene Proteins c-hck) RN - EC 2.7.10.2 (Proto-Oncogene Proteins c-yes) RN - EC 2.7.10.2 (Syk Kinase) RN - EC 2.7.10.2 (Syk protein, mouse) RN - EC 2.7.10.2 (Yes1 protein, mouse) RN - EC 2.7.10.2 (lyn protein-tyrosine kinase) RN - EC 2.7.10.2 (proto-oncogene proteins c-fgr) RN - EC 2.7.10.2 (src-Family Kinases) SB - IM MH - Actins/analysis MH - Animals MH - Biopolymers MH - Enzyme Inhibitors/pharmacology MH - Enzyme Precursors/antagonists & inhibitors/deficiency/genetics/*physiology MH - Immunoglobulin G/immunology MH - Intracellular Signaling Peptides and Proteins MH - Lysosomes/*physiology MH - Membrane Fusion/drug effects MH - Mice MH - Mice, Knockout MH - Microscopy, Confocal MH - Microscopy, Fluorescence MH - Microspheres MH - Opsonin Proteins/immunology MH - *Phagocytosis MH - Phagosomes/*physiology MH - Protein-Tyrosine Kinases/antagonists & inhibitors/deficiency/genetics/*physiology MH - Proto-Oncogene Proteins/antagonists & inhibitors/deficiency/genetics/physiology MH - Proto-Oncogene Proteins c-fyn MH - Proto-Oncogene Proteins c-hck MH - Proto-Oncogene Proteins c-yes MH - Pyrazoles/pharmacology MH - Pyrimidines/pharmacology MH - Receptors, IgG/*physiology MH - Saccharomyces cerevisiae MH - Stilbenes/pharmacology MH - Syk Kinase MH - src-Family Kinases/antagonists & inhibitors/deficiency/genetics/*physiology EDAT- 2001/11/08 10:00 MHDA- 2002/01/05 10:01 CRDT- 2001/11/08 10:00 PHST- 2001/11/08 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/11/08 10:00 [entrez] PST - ppublish SO - J Leukoc Biol. 2001 Nov;70(5):801-11.