Rab5-mediated recruitment of class III PI3K to TLR9 Engulfed CpG DNA binds to endosomal C-ter TLR9 Engulfed CpG DNA binds to endosomal N-ter TLR9 dimer Engulfed CpG DNA binds to endosomal full-length TLR9 PathwayStep6768 PathwayStep6766 PathwayStep6767 PathwayStep6763 PathwayStep6765 MyD88 dependent cascade initiated on endosome Toll Like Receptor 9 (TLR9) Cascade Authored: Luo, F, 2005-11-10 11:23:18 CpG DNA is an unusual Pathogen-Associated Molecular Pattern (PAMP). Cytosine methylation exists in mammalian but not bacterial cells, and most (but not all) CpG in the mammalian genome is methylated. Therefore, unmethylated CpG DNA may signal the presence of microbial infection. Evidence of CpG recognition by TLR9 was demonstrated both in human and mouse, and this type of signaling requires its internalization into late endosomal/lysosomal compartments. TLR9 has been reported to be able to discern different types of CpG motifs, and therefore that it presumably recognizes CpG DNA directly. It appears that over evolutionary periods, TLR9 molecules expressed by different species have diverged. This has led to differences in the precise sequence motif (CpG dinucleotide plus flanking regions) that optimally stimulate the innate immune system of different animals. Edited: Shamovsky, V, 2010-11-15 ISBN0781735149 Pubmed11130078 Pubmed11470918 Pubmed11564765 Pubmed14751759 Pubmed7700380 Pubmed9799232 Reactome Database ID Release 43168138 Reactome, http://www.reactome.org ReactomeREACT_9047 Reviewed: Gale M, Jr, 2006-10-31 16:45:01 Reviewed: Gillespie, ME, 2010-10-29