TRAM is involved in IL-18 signaling and functions as a sorting adaptor for MyD88.
TRAM is involved in IL-18 signaling and functions as a sorting adaptor for MyD88.
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DOI：
10.1371/journal.pone.0038423
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kondo N
中科院分区：
文献类型：
--
作者：
Ohnishi H;Tochio H;Kato Z;Kawamoto N;Kimura T;Kubota K;Yamamoto T;Funasaka T;Nakano H;Wong RW;Shirakawa M;Kondo N
MyD 88是一种含有Toll/白细胞介素-1受体同源（TIR）结构域的衔接蛋白，介导从Toll样受体（TLR）或IL-1/IL-18受体到下游激酶的信号。在MyD 88依赖性TLR 4信号传导中，MyD 88的功能被另一个含有TIR结构域的衔接子Mal/TIRAP增强，其将MyD 88带到质膜并促进其与TLR 4的胞质区域的相互作用。因此，Mal被认为是MyD 88的“分选适配器”。在这项研究中，MyD 88-TIR和另一种膜分选衔接子TRAM/TICAM-2之间的直接相互作用在体外得到了证实。包括RNA干扰实验和TRAM缺陷小鼠在内的基于细胞的测定揭示了细胞中MyD 88和TRAM之间的相互作用在介导IL-18信号转导中是重要的。活细胞成像进一步证明了MyD 88和TRAM在HEK 293细胞中的膜区域中的共定位积累。这些发现表明TRAM在IL-18信号转导中充当MyD 88的分选衔接子，从而促进信号转导。TRAM的结合位点位于MyD 88的TIR结构域中，并且实际上与Mal的结合位点重叠。MyD 88是与大多数TLR成员和IL-1/IL-18受体一起工作的多功能信号转导衔接子，其可以在不同的背景下以保守的方式与两种不同的分选衔接子TRAM和Mal相互作用。
MyD88, a Toll/interleukin-1 receptor homology (TIR) domain-containing adaptor protein, mediates signals from the Toll-like receptors (TLR) or IL-1/IL-18 receptors to downstream kinases. In MyD88-dependent TLR4 signaling, the function of MyD88 is enhanced by another TIR domain-containing adaptor, Mal/TIRAP, which brings MyD88 to the plasma membrane and promotes its interaction with the cytosolic region of TLR4. Hence, Mal is recognized as the “sorting adaptor” for MyD88. In this study, a direct interaction between MyD88-TIR and another membrane-sorting adaptor, TRAM/TICAM-2, was demonstrated in vitro. Cell-based assays including RNA interference experiments and TRAM deficient mice revealed that the interplay between MyD88 and TRAM in cells is important in mediating IL-18 signal transduction. Live cell imaging further demonstrated the co-localized accumulation of MyD88 and TRAM in the membrane regions in HEK293 cells. These findings suggest that TRAM serves as the sorting adaptor for MyD88 in IL-18 signaling, which then facilitates the signal transduction. The binding sites for TRAM are located in the TIR domain of MyD88 and actually overlap with the binding sites for Mal. MyD88, the multifunctional signaling adaptor that works together with most of the TLR members and with the IL-1/IL-18 receptors, can interact with two distinct sorting adaptors, TRAM and Mal, in a conserved manner in a distinct context.
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DOI：
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发表时间：
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影响因子：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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影响因子：
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