Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
Immunol Rev. 2009 Nov;232(1):42-58. doi: 10.1111/j.1600-065X.2009.00841.x.
The adapter proteins DAP12 and FcRgamma 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 FcRgamma contain specific protein domains (referred to as immunoreceptor tyrosine-based activation motifs) 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 immunoglobulin superfamily members but also cytokine receptors, integrins, and other adhesion molecules. There is abundant evidence that these multifunctional signaling adapters also mediate inhibitory activity, downmodulating signaling from Toll-like receptors and other heterologous receptors. In this review, we discuss the newly described receptors that utilize DAP12 and/or FcRgamma adapters to modulate innate immune responses.
衔接蛋白 DAP12 和 FcRγ 与各种先天免疫细胞中广泛的受体结合，当它们的同源受体被激活时，介导细胞内信号通路。这些衔接蛋白通过衔接蛋白和受体跨膜区的带电残基与受体偶联。DAP12 和 FcRγ 含有特定的蛋白结构域（称为免疫受体酪氨酸激活基序），作为激酶的底物和停泊点，从而放大细胞内信号反应。最近的研究拓宽了利用这些衔接蛋白进行信号转导的受体谱，不仅包括新型免疫球蛋白超家族成员，还包括细胞因子受体、整合素和其他黏附分子。有充分的证据表明，这些多功能信号衔接蛋白还介导抑制活性，下调 Toll 样受体和其他异源受体的信号转导。在这篇综述中，我们讨论了新描述的利用 DAP12 和/或 FcRγ 衔接蛋白来调节先天免疫反应的受体。
