Fc receptor gamma-chain, a constitutive component of the IL-3 receptor, is required for IL-3-induced IL-4 production in basophils.
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.
Hida
Shigeaki
S
Department of Immunology and Infectious Diseases, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan.
Yamasaki
Sho
S
Sakamoto
Yuzuru
Y
Takamoto
Masaya
M
Obata
Kazushige
K
Takai
Toshiyuki
T
Karasuyama
Hajime
H
Sugane
Kazuo
K
Saito
Takashi
T
Taki
Shinsuke
S
D000818:Animals; D001491:Basophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D005434:Flow Cytometry; D047468:Immunoprecipitation; D007377:Interleukin-3 / Q000276:immunology / Q000378:metabolism*; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016185:Receptors, Interleukin-3 / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology; D015533:Transcriptional Activation / Q000276:immunology
D007377:Interleukin-3; D047908:Intracellular Signaling Peptides and Proteins; D017452:Receptors, IgG; D016185:Receptors, Interleukin-3; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse