Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
J Immunol. 2012 Jan 15;188(2):527-30. doi: 10.4049/jimmunol.1102713. Epub 2011 Dec 14.
Compartmentalization of nucleic acid sensing TLR9 has been implicated as a mechanism to prevent recognition of self nucleic acid structures. Furthermore, recognition of CpG DNA in different endosomal compartments leads to the production of the proinflammatory cytokine TNF-α, or type I IFN. We previously characterized a tyrosine-based motif at aa 888-891 in the cytoplasmic tail of TLR9 important for appropriate intracellular localization. In this article, we show that this motif is selectively required for the production of TNF, but not IFN. In response to CpG DNA stimulation, the proteolytically processed 80-kDa fragment is tyrosine phosphorylated. Although Y888 is not itself phosphorylated, the structure of this motif is necessary for both TLR9 phosphorylation and TNF-α production in response to CpG DNA. We conclude that bifurcation in TLR9 signaling is regulated by a critical tyrosine motif in the cytoplasmic tail.
核酸感应 TLR9 的分隔已被认为是防止自身核酸结构识别的一种机制。此外，在不同的内体隔间中识别 CpG DNA 会导致促炎细胞因子 TNF-α或 I 型 IFN 的产生。我们之前描述了 TLR9 细胞质尾部 aa888-891 处的一个基于酪氨酸的基序，该基序对于适当的细胞内定位很重要。在本文中，我们表明该基序选择性地需要产生 TNF，但不需要 IFN。在 CpG DNA 刺激下，经过蛋白水解处理的 80 kDa 片段发生酪氨酸磷酸化。尽管 Y888 本身未磷酸化，但该基序的结构对于 TLR9 磷酸化和 CpG DNA 反应中 TNF-α 的产生都是必需的。我们得出结论，TLR9 信号的分叉由细胞质尾部的一个关键酪氨酸基序调节。
