Fc gamma receptor-mediated phagocytosis requires tyrosine kinase activity and is ligand independent.
Receptors for the invariant chain of immunoglobulins (FcR) define the cellular response to specific antigens. Fc gamma R recognize IgG and so elicit a variety of effector functions including phagocytosis. We are interested in the structural determinants for Fc gamma R-mediated phagocytosis, specifically Fc gamma RI(p135) and Fc gamma RIIa isoforms. The low-affinity receptor, Fc gamma RIIa, is found on macrophages and its cytoplasmic domain contains a tyrosine activation motif which has previously been shown to regulate endocytosis. In contrast, Fc gamma RI has no known signaling motifs, though a functional interaction has recently been demonstrated with the gamma chain of the high-affinity receptor for IgE, Fc epsilon RI. This accessory molecule has a cytoplasmic tyrosine activation motif implicated in signal transduction. Here we demonstrate that although Fc gamma RI transiently expressed on COS-7 cells is able to rosette opsonized SRBC, it cannot phagocytose them. If the cytoplasmic domain of either gamma chain or Fc gamma RIIa replaces that of Fc gamma RI in a chimeric receptor, efficient phagocytosis occurs. This particle ingestion is sensitive to the tyrosine kinase inhibitor genistein. Chimeric receptors where the extracellular domain of either Fc gamma RI or Fc gamma RIIa is replaced with that of CD2, a T cell antigen, indicate that Fc gamma R-mediated phagocytosis is ligand independent. We conclude that phagocytosis is dependent upon close particle apposition, tyrosine kinase activity, and that the process is ligand independent.
Hutchinson
M J
MJ
Division of Biochemistry and Molecular Biology, University of Glasgow.
Harrison
P T
PT
Floto
R A
RA
Allen
J M
JM
D000818:Animals; D001483:Base Sequence; D018801:CD2 Antigens / Q000502:physiology; D002478:Cells, Cultured; D008969:Molecular Sequence Data; D010587:Phagocytosis; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D017452:Receptors, IgG / Q000032:analysis / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012756:Sheep
D018801:CD2 Antigens; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases