J. Cell Biol.
© The Rockefeller University Press
0021-9525/97/12/1209/09 $2.00
Volume 139, Number 5, December 1, 1997 1209-1217

Role for a Glycan Phosphoinositol Anchor in Fc Receptor Synergy

Jennifer M. Green,^* Alan D. Schreiber, and Eric J. Brown^*

^* Division of Infectious Diseases, Washington University, School of Medicine, St. Louis, Missouri 63110; and  Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

While many cell types express receptors for the Fc domain of IgG (FcR), only primate polymorphonuclear neutrophils (PMN) express an FcR linked to the membrane via a glycan phosphoinositol (GPI) anchor. Previous studies have demonstrated that this GPI-linked FcR (FcRIIIB) cooperates with the transmembrane FcR (FcRIIA) to mediate many of the functional effects of immune complex binding. To determine the role of the GPI anchor in Fc receptor synergy, we have developed a model system in Jurkat T cells, which lack endogenously expressed Fc receptors. Jurkat T cells were stably transfected with cDNA encoding FcRIIA and/or FcRIIIB. Cocrosslinking the two receptors produced a synergistic rise in intracytoplasmic calcium ([Ca²⁺]_i) to levels not reached by stimulation of either FcRIIA or FcRIIIB alone. Synergy was achieved by prolonged entry of extracellular Ca²⁺. Cocrosslinking FcRIIA with CD59 or CD48, two other GPI-linked proteins on Jurkat T cells also led to a synergistic [Ca²⁺]_i rise, as did crosslinking CD59 with FcRIIA on PMN, suggesting that interactions between the extracellular domains of the two Fc receptors are not required for synergy. Replacement of the GPI anchor of FcRIIIB with a transmembrane anchor abolished synergy. In addition, tyrosine to phenylalanine substitutions in the immunoreceptor tyrosine-based activation motif (ITAM) of the FcRIIA cytoplasmic tail abolished synergy. While the ITAM of FcRIIA was required for the increase in [Ca²⁺]_i, tyrosine phosphorylation of crosslinked FcRIIA was diminished when cocrosslinked with FcRIIIB. These data demonstrate that FcRIIA association with GPI-linked proteins facilitates FcR signal transduction and suggest that this may be a physiologically significant role for the unusual GPI-anchored FcR of human PMN.

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