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. 2014 Aug 12;7:57. doi: 10.1186/s13045-014-0057-5

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Copyright © 2014 Isaza-Correa et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Signaling pathway of toll-like receptors (TLRs). After recognition of the ligand by the extracellular domain of TLRs, adaptor proteins are recruited to the TIR domain and initiate intracellular signaling. Four types of adaptor proteins have been identified in mammals: MyD88, TRIF, TRAM, and TIRAP. The recruitment of IRAK and TRAF6 to the adaptor proteins leads to nuclear translocation of NF-kB. TRAF6 can also activate MAPK kinases (MKK) leading to the activation of transcription factor AP-1. This pathway is common to all the TLRs, except for TLR3 which uses TANK-binding kinase 1 (TBK1) and results in the activation of IRF3.