Proteolytic cleavage in an endolysosomal compartment is required for activation of Toll-like receptor 9

@article{Park2008ProteolyticCI,
  title={Proteolytic cleavage in an endolysosomal compartment is required for activation of Toll-like receptor 9},
  author={Boyoun Park and Melanie M Brinkmann and Eric Spooner and Clarissa C. Lee and You-Me Kim and Hidde L. Ploegh},
  journal={Nature Immunology},
  year={2008},
  volume={9},
  pages={1407-1414}
}
Toll-like receptors (TLRs) activate the innate immune system in response to pathogens. Here we show that TLR9 proteolytic cleavage is a prerequisite for TLR9 signaling. Inhibition of lysosomal proteolysis rendered TLR9 inactive. The carboxy-terminal fragment of TLR9 thus generated included a portion of the TLR9 ectodomain, as well as the transmembrane and cytoplasmic domains. This cleavage fragment bound to the TLR9 ligand CpG DNA and, when expressed in Tlr9−/− dendritic cells, restored CpG DNA… CONTINUE READING
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