Cited by 54Phagocytosis and Immune RegulationCellular transport and secretionProtein Kinase Regulation and GTPase Signaling

Expression of the Protein Kinase C Substrate Pleckstrin in Macrophages: Association with Phagosomal Membranes

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Brumell, John H, Howard, Jeffrey C, Craig, Karen, Grinstein, Sergio, Schreiber, Alan D, Tyers, Mike·1999·The Journal of Immunology

Abstract

Despite evidence suggesting that protein kinase C (PKC) isoforms are important in phagocytosis by Fcγ receptors, the mechanisms by which the substrates of these kinases act are largely unknown. We have investigated the role of one PKC substrate, pleckstrin, in cells of the monocyte/macrophage lineage. Pleckstrin expression in mouse macrophages was induced severalfold in response to bacterial LPS and IFN-γ. In unstimulated cells, the protein was largely confined to the cytosol. Upon ingestion of IgG-opsonized zymosan particles (OPZ), however, pleckstrin accumulated on the phagosomal membrane. This association was transient, being maximal after 15 min and declining thereafter. Similar kinetics of association was also seen for both filamentous actin and the δ isoform of PKC. Ingestion of OPZ was found to induce phosphorylation of pleckstrin. To examine whether phosphorylation was required for phagosomal association, pleckstrin was expressed in CHO-IIA cells that stably express the FcγRIIA receptor and are competent for phagocytosis of OPZ. In these cells, both wild-type pleckstrin and mutants in which the phosphoacceptor sites had been mutated to either alanine (nonphosphorylatable) or glutamine (pseudophosphorylated) were found to accumulate on OPZ phagosomes. Thus, association of pleckstrin with phagosomes is independent of its phosphorylation. Our findings suggest that pleckstrin may serve as an intracellular adaptor/targeting protein in response to particulate stimuli. By targeting interacting ligands to the phagosomal compartment, pleckstrin may serve to regulate phagocytosis and/or early steps during maturation of the phagosome.

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Crossref · 10.4049/jimmunol.163.6.3388

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  • Both PKCα and PKCδ copurify with isolated phagosomal membranes, and some inhibitors of PKC activity have been reported to interfere with phagocytosis.

    “both PKCα and PKCδ copurify with isolated phagosomal membranes (Allen and Aderem 1995; Brumell et al. 1999) and some inhibitors of PKC activity have been reported to interfere with phagocytosis (Zheleznyak and Brown 1992; Karimi et al. 1999).”

    From Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis (2000) · cites this paper as Brumell et al. 1999

    The passage on phagosomal membranes reports that PKCδ accumulates on purified phagosomal membranes. It says conventional PKC isoforms have been found on phagosomes, but does not identify PKCα or establish its copurification. The inhibitor clause is attributed to other citations, not Brumell et al. (1999). (LLM, conf=0.87)

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Authors
Brumell, J. H., Howard, J. C., Craig, K., Grinstein, S., Schreiber, A. D., & Tyers, M.
Affiliations
  • Mount Sinai Hospital (CA)
  • Hospital for Sick Children (CA)
  • University of Pennsylvania (US)
Corresponding author
  • Craig, Karen
  • Tyers, Mike
Venue
The Journal of Immunology
Published
1999-09
Volume
163
Issue
6
Pages
3388-3395
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W1514153354
Cited by
54
References
54
Citations by year
2025: 1 · 2024: 2 · 2023: 1 · 2022: 6 · 2021: 2 · 2020: 1 · 2018: 1 · 2015: 1 · 2013: 1
FWCI
1.70
Type
journal article
Language
en
Open access
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • Medical Research Council Canada
  • National Institutes of Health (AI-22193)
  • Natural Sciences and Engineering Research Council of Canada
  • Medical Research Council
  • National Institute of Allergy and Infectious Diseases (AI-22193)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
pleckstrin, protein kinase C, macrophages, phagosome, phagocytosis, FCGR2A, zymosan, LPS, interferon-gamma, actin, phagosome maturation, adaptor proteins
MeSH terms
Animals, Blood Platelets, Blood Proteins, Cell Line, Cricetinae, Immunoglobulin G, Interferon-gamma, Intracellular Membranes, Lipopolysaccharides, Macrophage Activation, Macrophages, Mice, Inbred BALB C, Mice, Inbred C57BL, Monocytes, Opsonin Proteins, Phagocytosis, Phagosomes, Phosphoproteins, Phosphorylation, Protein Kinase C, Substrate Specificity, Zymosan, CHO Cells, Cell Lineage, Mice

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