Tyrosine phosphorylation is required for Fc receptor-mediated phagocytosis in mouse macrophages.

Abstract

SummaryAlthough Fc receptor-mediated phagocytosis is accompanied by a variety of transmembrane signaling events, not all signaling events are required for particle ingestion. For example, Fc receptor-mediated phagocytosis in mouse inflammatory macrophages (Di Virgilio, F., B. C. Meyer, S. Greenberg, and S. C. Silverstein. 1988. J. Cell Biol. 106:657; Greenberg, S., J. E1 Khoury, F. Di Virgilio, and S. C. Silverstein. 1991.J. Cell Biol. 113:757) and neutrophils (Della Bianca, V., M. Grzeskowiak, and F. Rossi. 1990. J. Immunol. 144:1411 occurs in the absence of cytosolic calcium transients. We sought to identify transmembrane signaling events that are essential for phagocytosis. Here we show that tyrosine phosphorylation is an early event after Fc receptor ligation in mouse inflammatory macrophages, and that the formation of tyrosine phosphoproteins coincides temporally with the appearance of F-actin beneath phagocytic cups. The distribution of tyrosine phosphoproteins that accumulated beneath phagocytic cups was punctate and corresponded to areas of high ligand density on the surface of the antibody-coated red blood cells, which provided the phagocytic stimulus. A tyrosine kinase inhibitor, genistein, but not several inhibitors of protein kinase C, blocked the appearance of tyrosine phosphoproteins as assessed by immunofluorescence, the focal accumulation of F-actin beneath immunoglobulin G-opsonized particles, and the ingestion of these particles as well. We suggest that tyrosine phosphorylation is a critical signaling event that underlies Fc receptor-mediated phagocytosis in mouse macrophages, and is necessary for the engulfment per se.

The Protein Tyrosine Phosphatase SHP-1 Regulates Phagolysosome Biogenesis

“…We report that SHP-1 is recruited early to phagosomes and that it is required for the acquisition of lysosomal features and acidification. Previous studies established that particle internalization is accompanied by the tyrosine phosphorylation of numerous proteins, through the action of Syk and Src family kinases (40)(41)(42)(43)(44). Investigation by Strzelecka-Kiliszek et al (21) showed that binding of IgG-coated particles to the surface of macrophages induces rapid and transient tyrosine phosphorylation of several proteins.…”

A Comparison of Mediators Released or Generated by IFN-γ-Treated Human Mast Cells Following Aggregation of FcγRI or FcεRI

“…The ␥-chain cytoplasmic domain contains immunoreceptor tyrosine-based activation motifs (ITAMs) and the ␥-chain cytoplasmic domain is both necessary and sufficient for Fc␥RI␣-induced functions (33,34). Biochemical studies have shown that both cross-linking of Fc⑀RI␣-␥-chain complex and the Fc␥RI␣-␥-chain complex result in activation of Src family kinases and the tyrosine kinase p72 Syk (4,(35)(36)(37)(38). Biological responses triggered by FcR with ITAMs seem to depend on the cell type more than on the receptor (4).…”

Localization of p21-activated kinase 1 (PAK1) to pseudopodia, membrane ruffles, and phagocytic cups in activated human neutrophils

“…Phagocytosis is controlled by signaling pathways triggered by the activation of cell surface Fc and complement C3b receptors that specifically bind opsonized particulate stimuli, and which involve the action of the Rho family GTPases [8,9]. Induced actin polymerization and subsequent pseudopod extension result in the formation of phagocytic cups, which then close to engulf the particle being ingested [3,[10][11][12]. The signaling molecules that direct the de novo polymerization of actin, and the ultimate organization of the polymerized actin into lamellipodia during chemotaxis and phagocytosis, remain to be clarified.…”