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Insertion of cytoplasmic tyrosine sequences into the nonphagocytic receptor
Fc gamma RIIB establishes phagocytic function
ZK Indik, XQ Pan, MM Huang, SE McKenzie, AI Levinson and AD Schreiber
University of Pennsylvania School of Medicine, Departments of Medicine and
Microbiology, Philadelphia.
Receptors for the Fc domain of IgG on cells of hematopoietic lineage
perform important functions, including stimulation of the ingestion of
IgG-coated cells. In examining the function of Fc gamma receptor isoforms
by transfection into COS-1 cells, we have observed that Fc gamma RIIA
induces the binding and phagocytosis of IgG-sensitized RBCs (EA) and that
transfected COS-1 cells can serve as a model for examining the molecular
structures involved in mediating a phagocytic signal. We now report that
COS-1 cell transfectants expressing the isoforms Fc gamma RIIB1 and Fc
gamma RIIB2 and a Fc gamma RIIA mutant without a cytoplasmic tail
efficiently bind EA but do not mediate their phagocytosis. Furthermore,
wild-type Fc gamma RIIA, but not Fc gamma RIIB1 or Fc gamma RBII2, was
phosphorylated on tyrosine upon receptor activation. Tyrphostin 23, which
alters tyrosine kinase activity, inhibited the phagocytosis of EA and
reduced the phosphorylation of Fc gamma RIIA on tyrosine. Fc gamma RIIB1
and Fc gamma RIIB2 contain one copy of the cytoplasmic sequence YXXL/I
implicated in signal transduction, whereas Fc gamma RIIA contains two
copies. We therefore inserted YXXL/I sequences at different sites in Fc
gamma RIIB2. Low levels of phagocytosis were observed in a Fc gamma RIIB2
mutant bearing the Fc gamma RIIA sequence YMTL and higher levels of
phagocytosis were observed in a second Fc gamma RIIB2 mutant that contained
both the upstream YMTL and an additional downstream tyrosine-containing
motif. Activation of this mutant receptor also induced receptor tyrosine
phosphorylation. Thus, these studies indicate that both the number and
placement of YXXL sequences in the cytoplasmic domain of the Fc gamma RII
receptor family affect both receptor tyrosine phosphorylation and
phagocytic competence.
Volume 83,
Issue 8,
pp. 2072-2080,
04/15/1994
Copyright © 1994 by The American Society of Hematology
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