Reactome | MyD88 cascade initiated on plasma membrane

MyD88 cascade initiated on plasma membrane

Stable Identifier

R-HSA-975871

Type

Pathway

Species

Homo sapiens

Related Species

Escherichia coli

ReviewStatus

5/5

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MyD88 cascade initiated on plasma membrane

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Mammalian myeloid differentiation factor 88 (MyD88) is Toll/interleukin (IL)-1 (TIR)-domain containing adapter protein which plays crucial role in TLR signaling. All TLRs, with only one exception of TLR3, can initiate downstream signaling trough MyD88. In the MyD88 - dependent pathway, once the adaptor is bound to TLR it leads to recruitment of IL1 receptor associated kinase family IRAK which is followed by activation of tumour necrosis factor receptor-associated factor 6 (TRAF6) . TRAF6 is an ubiquitin E3 ligase which in turn induces TGF-beta activating kinase 1 (TAK1) auto phosphorylation. Once activated TAK1 can ultimately mediate the induction of the transcription factor NF-kB or the mitogen-activated protein kinases (MAPK), such as JNK, p38 and ERK. This results in the translocation of the activated NF-kB and MAPKs to the nucleus and the initiation of appropriate gene transcription leading to the production of many proinflammatory cytokines and antimicrobial peptides.

Literature References

PubMed ID	Title	Journal	Year
16239509	Human airway epithelial cells sense Pseudomonas aeruginosa infection via recognition of flagellin by Toll-like receptor 5 Louboutin, JP, Weiner, DJ, Wilson, JM, Zhang, Z, Goldberg, JB	Infect Immun	2005
15728506	Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88 Merck, E, Chaffois, C, Trinchieri, G, Vlach, J, Saulnier, V, Hasan, U, Lebecque, S, Briere, F, Bates, EE, Tancredi, S, Guiet, C, Gaillard, C	J Immunol	2005