TYROSINE-CONTAINING SEQUENCE MOTIFS OF THE HUMAN-IMMUNOGLOBULIN-G RECEPTORS FCRIIB1 AND FCRIIB2 ESSENTIAL FOR ENDOCYTOSIS AND REGULATION OFCALCIUM FLUX IN B-CELLS
P. Budde et al., TYROSINE-CONTAINING SEQUENCE MOTIFS OF THE HUMAN-IMMUNOGLOBULIN-G RECEPTORS FCRIIB1 AND FCRIIB2 ESSENTIAL FOR ENDOCYTOSIS AND REGULATION OFCALCIUM FLUX IN B-CELLS, The Journal of biological chemistry, 269(48), 1994, pp. 30636-30644
Human B cells express two closely related immunoglobulin G receptors,
FcRIIb1 and FcRIIb2, which differ by a 19 amino acid insertion in the
cytoplasmic tail of FcRIIb1. The cytoplasmic tails of both isoforms co
ntain a conserved sequence motif (AENTITYSLL) essential for mediating
endocytosis via FcRIIb2. Truncation of this motif abolished endocytosi
s, while replacement of tyrosine (Tyr-(273)) in FcRIIba by phenylalani
ne had no effect on the amount and kinetics of ligand uptake. Co-cross
linking of FcRIIb1 or FcRIIb2 with the antigen receptor on B cells led
to an abortive calcium signal. Neither isoform interfered with the ea
rly intracellular calcium mobilization, but both prevented the opening
of a plasma membrane calcium channel essential for a sustained elevat
ed intracellular calcium level. Modulation of calcium channel activity
is mediated by the same sequence motif essential for endocytosis but
requires the pres- ence of Tyr(292) in FcRIIb1 and Tyr(273) in, FcRIIb
2. Co-crosslinking of FcRIIb1 with surface IgG is associated with tyro
sine phosphorylation of Tyr(292), whereas Tyr(272) in FcRIIb2 was not
phosphorylated. Thus, FcRIIb phosphorylation is probably not directly
involved in the modulation of the calcium signal but may be essential
for further diversification of signals transduced via the coexpressed
isoforms FcRIIb1 and FcRIIb2.