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*
Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada;
Division of Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada;
Hematology and Oncology Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; and
§
Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada
Despite evidence suggesting that protein kinase C (PKC) isoforms
are important in phagocytosis by Fc
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-. 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 
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 FcRIIA 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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