Involvement of phosphatidylinositol 3-kinase in Fc gamma receptor signaling.
Open accessAbstract
Wortmannin, a potent and selective inhibitor of phosphatidylinositol (PI) 3-kinase (Okada, T., Sakuma, L., Fukui, Y., Hazeki, O., and Ui, M. (1994) J. Biol. Chem. 269, 3563-3567), prevented Fc receptor for IgG (Fc gamma R)-dependent phagocytosis of the human monocytic cell line U937 or guinea pig neutrophils. Cross-linking of Fc gamma R on the surface of U937 cells increased PI 3-kinase activity that was immunoprecipitated with antibody against phosphotyrosine or antibody against the 85-kDa regulatory subunit of PI 3-kinase. Specific cross-linking of Fc gamma R subclass Fc gamma RI or Fc gamma RII, using monoclonal antibodies against each receptor subclass and the F(ab')2 fragment of goat antibody against mouse IgG, increased anti-phosphotyrosine-precipitable PI 3-kinase activity. Treatment of cells with anti-Fc gamma RIII antibody plus the same F(ab')2 did not affect the activity, reflecting the lack of Fc gamma RIII in U937 cells. Fcy gamma R stimulation triggered prominent tyrosine phosphorylation of several proteins, among which the 115-kDa peptide showed strong association with PI 3-kinase. Thus, Fc gamma R appears to be coupled functionally, via a tyrosine kinase, to PI 3-kinase, which may regulate the phagocytotic activity of the cells.
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PI3K appears essential for phagocytosis because inhibitors such as wortmannin impair particle engulfment.
“This kinase appears to be essential for phagocytosis since inhibitors such as wortmannin impair particle engulfment (Ninomiya et al. 1994; Araki et al. 1996; Cox et al. 1999).”
From Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis (2000) · cites this paper as Ninomiya et al. 1994
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“This kinase appears to be essential for phagocytosis since inhibitors such as wortmannin impair particle engulfment (Ninomiya et al., 1994; Araki et al., 1996; Cox et al., 1999).”
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- Authors
- Ninomiya, N., Hazeki, K., Fukui, Y., Seya, T., Okada, T., Hazeki, O., & Ui, M.
- Affiliations
- RIKEN (JP)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1994-09
- Volume
- 269
- Issue
- 36
- Pages
- 22732-22737
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1589063951
- Cited by
- 210
- References
- 1
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 5 · 2018: 1 · 2017: 7 · 2016: 7 · 2015: 4 · 2014: 1 · 2013: 5 · 2012: 2
- FWCI
- 13.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- phosphatidylinositol 3-kinase, Fcγ receptor signaling, wortmannin, phagocytosis, U937 cells, neutrophils, receptor cross-linking, tyrosine phosphorylation, FcγRI, FcγRII
- MeSH terms
- Wortmannin, Androstadienes, Animals, Cell Line, Guinea Pigs, Humans, Neutrophils, Phagocytosis, Phospholipase D, Phosphopeptides, Phosphorylation, Protein-Tyrosine Kinases, Tumor Cells, Cultured, Tyrosine, Signal Transduction, Receptors, IgG, Phosphotransferases (Alcohol Group Acceptor), Phosphotyrosine, Phosphatidylinositol 3-Kinases, Macromolecular Substances, In Vitro Techniques
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