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Identification of signaling motifs within human Fc gamma RIIa and Fc gamma
RIIb isoforms
IE Van den Herik-Oudijk, PJ Capel, T van der Bruggen and JG Van de Winkel
Department of Immunology, University Hospital Utrecht, The Netherlands.
To assess the functional capacity of the heterogeneous Fc gamma RII (CD32)
family and to identify critical regions for functioning, we generated a
panel of B-cell transfectants. The Fc gamma R-negative B- cell line IIA1.6
was transfected with wild-type or mutant human Fc gamma RIIa and IIb
molecules. Solely Fc gamma RIIa-expressing IIA1.6 cells were capable of
phagocytosing opsonized Staphylococcus aureus bacteria, and cross-linking
of Fc gamma RIIa triggered a rapid induction of tyrosine phosphorylation
after 20 seconds. Analysis of Fc gamma RIIa mutants identified the
immunoreceptor tyrosine-based activation motif (ITAM; previously described
as ARH-1 motif) within the IIa cytoplasmic tail to be critical for B-cell
activation. In contrast, Fc gamma RIIb isoforms triggered tyrosine
phosphorylation on cross- linking with much slower kinetics (> 3
minutes) than Fc gamma RIIa. Furthermore, solely Fc gamma RIIb molecules
proved capable of downregulating [Ca2+]i and interleukin-2 production on
co-cross-linking with sIgG in IIA1.6. The Fc gamma RIIb-mediated functions
were absent in Fc gamma RIIb mutants in which the tyrosine or leucine
within the YSLL motif in a conserved 13-aa region (now known as
immunoreceptor tyrosine-based inhibitor motif [ITIM]) were changed into
phenylalanines. In conclusion, these data show the presence of functionally
critical motifs within Fc gamma RII cytoplasmic tails. Fc gamma RIIa
contains an ITAM involved in B-cell activatory functions, whereas the
downregulatory activity of Fc gamma RIIb isoforms is linked to an ITIM.
Volume 85,
Issue 8,
pp. 2202-2211,
04/15/1995
Copyright © 1995 by The American Society of Hematology

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