The expanding roles of ITAM adapters FcRgamma and DAP12 in myeloid cells.
The expanding roles of ITAM adapters FcRgamma and DAP12 in myeloid cells.
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DOI：
10.1111/j.1600-065x.2009.00841.x
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发表时间：
2009-11
影响因子：
8.7
通讯作者：
Lowell CA
中科院分区：
文献类型：
--
作者：
Hamerman JA;Ni M;Killebrew JR;Chu CL;Lowell CA
衔接蛋白DAP 12和FcRγ与多种先天免疫细胞中的广谱受体缔合，以在其同源受体接合时介导细胞内信号传导途径。这些衔接子蛋白通过衔接子和受体的跨膜区内的带电残基与其受体偶联。DAP 12和FcRγ含有特异性蛋白质结构域（称为ITAM结构域），其作为激酶的底物和对接位点，允许扩增细胞内信号传导反应。最近的研究已经拓宽了利用这些衔接子进行信号传导的受体的库，不仅包括新的Ig超家族成员，而且包括细胞因子受体、整合素和其他粘附分子。更令人惊讶的是，有大量证据表明，这些多功能信号适配器也介导抑制活性，下调来自TLR和其他异源受体的信号。本文综述了近年来发现的利用DAP 12和/或FcRγ接头调节先天性免疫反应的受体。
The adapter proteins DAP12 and FcRγ associate with a wide spectrum of receptors in a variety of innate immune cells to mediate intracellular signaling pathways when their cognate receptor is engaged. These adapter proteins are coupled to their receptors through charged residues within the transmembrane regions of the adapter and receptor. DAP12 and FcRγ contain specific protein domains (referred to as ITAM domains) that serve as the substrates and docking sites for kinases allowing amplification of intracellular signaling reactions. Recent research has broadened the repertoire of receptors that utilize these adapters for signaling to include not only novel Ig-superfamily members but also cytokine receptors, integrins and other adhesion molecules. Even more amazing, there is abundant evidence that these multifunctional signaling adapters also mediate inhibitory activity, downmodulating signaling from TLRs and other heterologous receptors. In this review, we discuss the newly described receptors that utilize DAP12 and/or FcRγ adapters to modulate innate immune responses.