The cytoplasmic tail of FcgammaRIIIAalpha is involved in signaling by the low affinity receptor for immunoglobulin G.
The low affinity receptor for IgG, FcgammaRIIIA, is a multimeric receptor composed of the ligand binding subunit FcgammaRIIIAalpha (CD16) in association with the signal-transducing subunits zeta or gamma. Previous studies suggested that the cytoplasmic tail of FcgammaRIIIAalpha was not required for FcgammaRIIIAalpha-zeta association or signaling by FcgammaRIIIA. However, in these studies, the truncated FcgammaRIIIAalpha chains still expressed the four most membrane-proximal amino acids of the cytoplasmic tail (amino acids 230-233). By successive truncations from the C terminus of FcgammaRIIIAalpha, we have studied the role played by the membrane-proximal amino acids of the cytoplasmic tail of FcgammaRIIIAalpha in (i) FcgammaRIIIA expression, (ii) FcgammaRIIIAalpha-zeta association, and (iii) signal transduction. We provide evidence that this region is not required for FcgammaRIIIA expression or FcgammaRIIIAalpha-zeta association. However, signaling by FcgammaRIIIA is strictly dependent on the membrane-proximal amino acids in the cytoplasmic tail of FcgammaRIIIAalpha. Thus, total deletion of the cytoplasmic tail of FcgammaRIIIAalpha results in a severely impaired tyrosine phosphorylation of phospholipase C-gamma1, zap, and syk and rise in intracellular free Ca2+ following receptor ligation with specific anti-CD16 monoclonal antibody or Ig-anti-Ig complexes, suggesting that FcgammaRIIIAalpha-zeta association per se is not sufficient to establish the signal function of FcgammaRIIIA. In conclusion, the present findings demonstrate that the most membrane-proximal amino acids of the FcgammaRIIIAalpha cytoplasmic tail play a critical role in ligand-induced signal transduction by the FcgammaRIIIAalpha-zeta complex.
Hou
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Institute of Medical Microbiology and Immunology, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Dietrich
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J
Geisler
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NO
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017433:Protein Structure, Secondary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism*; D015398:Signal Transduction; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
D017452:Receptors, IgG; D011505:Protein-Tyrosine Kinases