W. Davis et al., 2 DISTINCT REGIONS OF FC-GAMMA-RI INITIATE SEPARATE SIGNALING PATHWAYS INVOLVED IN ENDOCYTOSIS AND PHAGOCYTOSIS, EMBO journal, 14(3), 1995, pp. 432-441
Cross-linking of the high affinity receptor for IgG, Fc gamma RI, can
result in both endocytosis of immune complexes and phagocytosis of ops
onized particles in myeloid cells, although the cytoplasmic domain of
the receptor lacks the tyrosine activation motif which has been implic
ated in signal transduction triggered by cross-linking of other Fc rec
eptors. To identify the structural determinants of Fc gamma RI-mediate
d ligand internalization, we have expressed Fc gamma RI or truncated v
ersions of Fc gamma RI in COS cells, either alone or in the presence o
f the Fc epsilon RI gamma subunit (which contains a classical tyrosine
activation motif and associates with Fc gamma RI in myeloid cells), a
nd assessed their ability to mediate endocytosis and phagocytosis. We
have found that Fc gamma RI alone (in the absence of the gamma subunit
) is capable of mediating endocytosis in COS cells and that the proces
s occurs via a novel, tyrosine kinase-independent signalling pathway.
Activation of this pathway following cross-linking appears to require
only the receptor extracellular domain. In contrast, Fc gamma RI phago
cytic function in COS cells is dependent on an interaction between the
receptor transmembrane domain and the gamma subunit and is mediated b
y recruitment of tyrosine kinase activity. Our data therefore indicate
that distinct domains of the receptor regulate ligand internalization
following receptor cross-linking by either immune complexes (endocyto
sis) or opsonized particles (phagocytosis) and that these functions ar
e mediated by different intracellular signalling pathways.