© The Rockefeller University Press,
0021-9525/1997//1209 $5.00
The Journal of Cell Biology, Volume 139, Number 5,
, 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 (Fc
R), only primate polymorphonuclear neutrophils (PMN) express an Fc
R linked to the membrane via a glycan phosphoinositol (GPI) anchor. Previous studies have demonstrated that this GPI-linked Fc
R (Fc
RIIIB) cooperates with the transmembrane Fc
R (Fc
RIIA) 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 Fc
RIIA and/or Fc
RIIIB. Cocrosslinking the two receptors produced a synergistic rise in intracytoplasmic calcium ([Ca2+]i) to levels not reached by stimulation of either Fc
RIIA or Fc
RIIIB alone. Synergy was achieved by prolonged entry of extracellular Ca2+. Cocrosslinking Fc
RIIA 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 Fc
RIIA 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 Fc
RIIIB with a transmembrane anchor abolished synergy. In addition, tyrosine to phenylalanine substitutions in the immunoreceptor tyrosine-based activation motif (ITAM) of the Fc
RIIA cytoplasmic tail abolished synergy. While the ITAM of Fc
RIIA was required for the increase in [Ca2+]i, tyrosine phosphorylation of crosslinked Fc
RIIA was diminished when cocrosslinked with Fc
RIIIB. These data demonstrate that Fc
RIIA association with GPI-linked proteins facilitates Fc
R signal transduction and suggest that this may be a physiologically significant role for the unusual GPI-anchored Fc
R of human PMN.
Abbreviations used in this paper: [Ca2+]i, intracytoplasmic Ca2+ concentration; GPI, glycan phosphoinositol; ITAM, immunoreceptor tyrosine-based activation motif; PLC, phospholipase C; PMN, polymorphonuclear neutrophils.
Address all correspondence to Dr. Eric J. Brown, Division of Infectious Diseases, Washington University School of Medicine, 660 S. Euclid Ave., Box 8051, St. Louis, MO 63110. Tel.: (314)362-2125. Fax: (314) 362-9230. E-mail: ebrown{at}id.wustl.edu

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