Role of Src kinases and Syk in Fcγ receptor-mediated phagocytosis and phagosome-lysosome fusion
Abstract
Phagocytosis is increased by Fcγ receptors (FcγRs), and studies with syk−/− macrophages demonstrated that Syk kinase is required for FcγR 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.
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Activation of Src/Syk kinases together with PI-3 kinase proteins induces downstream transcriptional activation of pro-inflammatory cytokines.
“The activation of Src/Syk kinases together with PI-3 kinase proteins further induces downstream transcriptional activation of pro-inflammatory cytokines [18].”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [18]
Inhibition of SYK blocks phagosome maturation.
“and inhibition of SYK blocks phagosome maturation (13).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [13]
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“The activation of Src/Syk kinases together with PI-3 kinase proteins further induces downstream transcriptional activation of pro-inflammatory cytokines [18].”
BackgroundMERTK interactions with SH2-domain proteins in the retinal pigment epithelium
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- Authors
- Majeed, M., Caveggion, E., Lowell, C. A., & Berton, G.
- Affiliations
- University of Verona (IT)
- University of California, San Francisco (US)
- Corresponding author
- Majeed, Meytham
- ORCID
- Lowell, Clifford A
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-11-01
- Volume
- 70
- Issue
- 5
- Pages
- 801-811
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W4312243655
- Cited by
- 97
- References
- 49
- Citations by year
- 2026: 8 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 8 · 2015: 4 · 2014: 3 · 2013: 3 · 2012: 4
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- Src family kinases, Syk, Fc gamma receptor, phagocytosis, phagosome-lysosome fusion, macrophages, Hck, Fgr, Lyn kinase, Fyn, Yes, tyrosine kinase inhibitors, protein phosphatase 1, piceatannol, opsonization
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