O. Malbec et al., FC-EPSILON RECEPTOR-I ASSOCIATED LYN-DEPENDENT PHOSPHORYLATION OF FC-GAMMA RECEPTOR IIB DURING NEGATIVE REGULATION OF MAST-CELL ACTIVATION, The Journal of immunology, 160(4), 1998, pp. 1647-1658
Fc gamma RIIB are low-affinity receptors for IgG whose intracytoplasmi
c domain contains an immunoreceptor tyrosine-based inhibition motif (I
TIM). Fc gamma RIIB inhibit cell activation triggered by receptors tha
t signal via immunoreceptor tyrosine-based activation motifs, This inh
ibition requires ITIM tyrosyl phosphorylation and is correlated with t
he binding of SH2 domain-containing phosphatases that may mediate the
inhibitory signal. In the present work, we investigated the mechanism
of Fc gamma RIIB phosphorylation and its consequences in mast cells. W
e demonstrate that the phosphorylation of Fc gamma RIIB requires coagg
regation with Fc epsilon RI and that, once phosphorylated, Fc gamma RI
IB selectively recruit the inositol polyphosphate 5 phosphatase SHIP,
in vivo. In vitro, however, the phosphorylated Fc gamma RIIB ITIM bind
s not only SHIP, but also the two protein tyrosine phosphatases, SHP-1
and SHP-2, We show that the coaggregation of Fc gamma RIIB with Fc ep
silon RI does not prevent Fc epsilon RI-mediated activation of lyn and
syk, Both kinases can phosphorylate Fc gamma RIIB in vitro. However,
when coaggregated with Fc epsilon RI, Fc gamma RIIB was in vice phosph
orylated in syk-deficient mast cells, but not in lyn-deficient mast ce
lls. When Fc epsilon RI are coaggregated with Fc gamma RIIB by immune
complexes, Fc epsilon RI-associated lyn may thus phosphorylate Fc gamm
a RIIB. By this mechanism, Fc epsilon RI initiate ITIM-dependent inhib
ition of intracellular propagation of their own signals.