Hida Shigeaki, Yamasaki Sho, Sakamoto Yuzuru, Takamoto Masaya, Obata Kazushige, Takai Toshiyuki, Karasuyama Hajime, Sugane Kazuo, Saito Takashi, Taki Shinsuke
Department of Immunology and Infectious Diseases, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan.
Nat Immunol. 2009 Feb;10(2):214-22. doi: 10.1038/ni.1686. Epub 2008 Dec 21.
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.
Fc受体共同γ链（FcRγ）是一种广泛表达的衔接蛋白，带有基于免疫受体酪氨酸的激活基序（ITAM），可转导来自各种免疫受体的激活信号。我们在此表明，缺乏FcRγ的嗜碱性粒细胞发育正常，对白细胞介素3（IL-3）有高效增殖反应，但在IL-3诱导的IL-4产生以及支持2型辅助性T细胞分化方面严重受损。通过其跨膜部分，FcRγ与IL-3受体的共同β链组成性结合，并通过募集激酶Syk发出信号。逆转录病毒介导的互补作用证明了FcRγ的ITAM在IL-3信号转导中的重要功能。我们的结果确定了一种以前未知的机制，通过该机制FcRγ发挥作用，将选择性细胞因子触发的信号“导向”ITAM介导的IL-4产生途径。
