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Determinants of the Phagocytic Signal Mediated by the Type IIIA Fcγ Receptor, FcγRIIIA: Sequence Requirements and Interaction with Protein-Tyrosine Kinases

Jong-Gu Park and Alan D. Schreiber
Proceedings of the National Academy of Sciences of the United States of America
Vol. 92, No. 16 (Aug. 1, 1995), pp. 7381-7385
Stable URL: http://www.jstor.org/stable/2368248
Page Count: 5
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Determinants of the Phagocytic Signal Mediated by the Type IIIA Fcγ Receptor, FcγRIIIA: Sequence Requirements and Interaction with Protein-Tyrosine Kinases
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Abstract

The Fcγ receptor-associated γ and ζ subunits contain a conserved cytoplasmic motif, termed the immunoglobulin gene tyrosine activation motif, which contains a pair of YXXL sequences. The tyrosine residues within these YXXL sequences have been shown to be required for transduction of a phagocytic signal. We have previously reported that the γ subunit of the type IIIA Fcγ receptor (FcγRIIIA) is ≈6 times more efficient in mediating phagocytosis than the ζ subunit of FcγRIIIA. By exchanging regions of the cytoplasmic domains of the homologous γ and ζ chains, we observed that the cytoplasmic area of the γ chain bearing a pair of the conserved YXXL sequences is important in phagocytic signaling. Further specificity of phagocytic signaling is largely determined by the two internal XX amino acids in the YXXL sequences. In contrast, the flanking amino acids of the YXXL sequences including the seven intervening amino acids between the two YXXL sequences do not significantly affect the phagocytic signal. Furthermore, the protein-tyrosine kinase Syk, but not the related kinase ZAP-70, stimulated FcγRIIIA-mediated phagocytosis. ZAP-70, however, increased phagocytosis when coexpressed with the Src family kinase Fyn. These data demonstrate the importance of the two specific amino acids within the γ subunit YXXL cytoplasmic sequences in phagocytic signaling and explain the difference in phagocytic efficiency of the γ and ζ chains. These results indicate the importance of Syk in FcγRIIIA-mediated phagocytosis and demonstrate that ZAP-70 and Syk differ in their requirement for a Src-related kinase in signal transduction.

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