Tyrosine-containing sequence motifs of the human immunoglobulin G receptors FcRIIb1 and FcRIIb2 essential for endocytosis and regulation of calcium flux in B cells.
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 contain a conserved sequence motif (AENTITYSLL) essential for mediating endocytosis via FcRIIb2. Truncation of this motif abolished endocytosis, while replacement of tyrosine (Tyr273) in FcRIIb2 by phenylalanine 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 early intracellular calcium mobilization, but both prevented the opening of a plasma membrane calcium channel essential for a sustained elevated intracellular calcium level. Modulation of calcium channel activity is mediated by the same sequence motif essential for endocytosis but requires the presence of Tyr292 in FcRIIb1 and Tyr273 in FcRIIb2. Co-cross-linking of FcRIIb1 with surface IgG is associated with tyrosine phosphorylation of Tyr292, whereas Tyr272 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.
Budde
P
P
Universität Bielefeld, Fakultät für Chemie, Germany.
Bewarder
N
N
Weinrich
V
V
Schulzeck
O
O
Frey
J
J
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003432:Cross-Linking Reagents; D004705:Endocytosis; D006706:Homeostasis; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D019000:Phosphotyrosine; D016133:Polymerase Chain Reaction; D017452:Receptors, IgG / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D003432:Cross-Linking Reagents; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D017452:Receptors, IgG; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D002118:Calcium