Drosophila peptidoglycan recognition protein LC (PGRP-LC) acts as a signal-transducing innate immune receptor
Drosophila peptidoglycan recognition protein LC (PGRP-LC) acts as a signal-transducing innate immune receptor
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DOI：
10.1073/pnas.0404952102
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发表时间：
2005-01-25
影响因子：
11.1
通讯作者：
Anderson, KV
中科院分区：
文献类型：
--
作者：
Choe, KM;Lee, H;Anderson, KV
果蝇肽聚糖识别蛋白LC（PGRP-LC）是一种对细菌感染应答所需的跨膜蛋白，在细胞质信号级联的顶端起作用，该信号级联需要死亡结构域蛋白Imd和licB激酶来激活NF-κ B家族成员Relish。尚不清楚肽聚糖与PGRP-LC的胞外结构域的结合如何激活胞内信号传导，因为其胞质结构域与表征的蛋白质没有同源性。在这里，我们证明，PGRP-LC结合Imd和它的胞质结构域是其活性的关键，这表明PGRP-LC作为一个信号转导受体。PGRP-LC胞质结构域也是形成二聚体所必需的，结果表明，受体活化可能需要二聚化。PGRP-LC胞质结构域可以介导不同PGRP-LC同种型之间的异二聚体的形成，从而潜在地扩大可以被受体识别的配体的多样性。
Drosophila peptidoglycan recognition protein LC (PGRP-LC), a transmembrane protein required for the response to bacterial infection, acts at the top of a cytoplasmic signaling cascade that requires the death-domain protein Imd and an licB kinase to activate Relish, an NF-kappaB family member. It is not clear how binding of peptidoglycan to the extracellular domain of PGRP-LC activates intracellular signaling because its cytoplasmic domain has no homology to characterized proteins. Here, we demonstrate that PGRP-LC binds Imd and that its cytoplasmic domain is critical for its activity, suggesting that PGRP-LC acts as a signal-transducing receptor. The PGRP-LC cytoplasmic domain is also essential for the formation of dimers, and results suggest that dimerization may be required for receptor activation. The PGRP-LC cytoplasmic domain can mediate formation of heterodimers between different PGRP-LC isoforms, thereby potentially expanding the diversity of ligands that can be recognized by the receptor.