TLR4 somehow manages to activate both MyD88- and TRIF-dependent signaling. According to Medzhitov and colleagues, TLR4 engages MyD88 and TRIF sequentially at the cell surface and in endosomes, respectively, thereby providing access to distinct pools of signaling proteins.
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Watts, C. Location, location, location: identifying the neighborhoods of LPS signaling. Nat Immunol 9, 343–345 (2008). https://doi.org/10.1038/ni0408-343
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DOI: https://doi.org/10.1038/ni0408-343
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