Abstract
The Fc receptor common gamma-chain (FcRgamma) is a widely expressed adaptor bearing an immunoreceptor tyrosine-based activation motif (ITAM) that transduces activation signals from various immunoreceptors. We show here that basophils lacking FcRgamma developed normally and proliferated efficiently in response to interleukin 3 (IL-3) but were very impaired in IL-3-induced production of IL-4 and in supporting T helper type 2 differentiation. Through its transmembrane portion, FcRgamma associated constitutively with the common beta-chain of the IL-3 receptor and signaled by recruiting the kinase Syk. Retrovirus-mediated complementation demonstrated the essential function of the ITAM of FcRgamma in IL-3 signal transduction. Our results identify a previously unknown mechanism whereby FcRgamma functions to 'route' selective cytokine-triggered signals into the ITAM-mediated IL-4 production pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basophils / cytology
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Basophils / immunology
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Basophils / metabolism*
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Blotting, Western
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Cell Differentiation / immunology
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Cell Proliferation
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Flow Cytometry
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Immunoprecipitation
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Interleukin-3 / immunology
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Interleukin-3 / metabolism*
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Interleukin-4 / biosynthesis*
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Interleukin-4 / immunology
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Intracellular Signaling Peptides and Proteins / immunology
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Intracellular Signaling Peptides and Proteins / metabolism
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Mice
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Mice, Transgenic
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Protein-Tyrosine Kinases / immunology
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Protein-Tyrosine Kinases / metabolism
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Receptors, IgG / genetics
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Receptors, IgG / immunology
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Receptors, IgG / metabolism*
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Receptors, Interleukin-3 / immunology
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Receptors, Interleukin-3 / metabolism
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Signal Transduction / immunology*
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Syk Kinase
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Th2 Cells / cytology
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Th2 Cells / immunology
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Transcriptional Activation / immunology
Substances
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Interleukin-3
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Intracellular Signaling Peptides and Proteins
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Receptors, IgG
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Receptors, Interleukin-3
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Interleukin-4
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Protein-Tyrosine Kinases
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Syk Kinase
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Syk protein, mouse