CD284 (Toll-Like Receptor 4 (TLR-4)) / MYD88 / NFKB signaling pathway

CD284 (Toll-Like Receptor 4 (TLR-4)) is an exception as it is the only Toll-Like Receptors (TLRs) that utilizes both MyD88-dependent and TRIF-Dependent Pathway
Chen et al. 2019m J. Biomed. Sci. 26: 90

The agonists Lipopolysaccharides (LPS) and RSV F protein lead to dimerization. The two adapter molecules, TIR domain containing adaptor protein (TIRAP) and Myeloid Differentiation Primary Response 88 (MYD88) are activated.

All TLR subtypes except Toll-like receptor 3 (TLR-3) (which contains another adapter protein called adapter-inducing interferon-β, TIR domain containing adaptor molecule 1 (TICAM1) , containing TIR domains) show MyD88-dependent signaling
Chen et al. 2019m J. Biomed. Sci. 26: 90

TLR-4 signaling is an essential causative pathway in the epithelial barrier defects observed in the Nr1i2 −/− mice
Venkatesh et al. 2014 Immunity 41: 296-310

The CD284 (Toll-Like Receptor 4 (TLR-4)) as a homodimer initiates an intracellular signaling cascade through adaptor proteins, primarily, Myeloid Differentiation Primary Response 88 (MYD88). After activation of the intermediate stage, the serine / threonine kinases IRAK1 and IRAK4 (not shown)(brain://K18yp1Fu9lCQj6W-cUNQPQ/Irak4), the IkB kinase (IKK) complex is activated, which initiates the activation and translocation of the NFKB. This leads to Activator protein 1 / Transcription Factor AP-1 (AP-1)-dependent transcription of the pro-inflammatory genes for IL-1 beta and IL-18.

The interaction with CD284 (Toll-Like Receptor 4 (TLR-4)) complexed with the transmembrane protein lymphocyte antigen 96 evokes the activation of myeloid differentiation primary response gene 88 (MyD88)-dependent pathway, leading to the induction of pro-inflammatory cytokines through NFKB
Abreu 2010 Nature Rev. Immunology 10: 131

MyD88 and TIR domain containing adaptor molecule 1 (TICAM1) regulate NFKB activation and nuclear translocation. However, TIR domain containing adaptor molecule 1 (TICAM1) uniquely activates the transcription factor Interferon (IFN) Regulatory Factor 3 (IRF3), leading to the expression of Interferons Type I (IFN Type I)
Kagan et al. 2008 Nat. Immunol. 9: 361-368

Receptor-associated Myeloid Differentiation Primary Response 88 (MYD88) recruits Interleukin-1 receptor-associated kinase 4 (IRAK4) and Interleukin-1 receptor-associated kinase-1 (IRAK1), which then associate with TNF receptor-associated Factor 6 (TRAF6). TRAF6 then activates transforming growth factor-β-Activated Kinase 1 (TAK1), which subsequently activates IkB kinase (IKK), JNK (c-Jun N-terminal kinase), and p38 MAP kinases, ultimately leading to early-phase NF kappa B (NFKB) / NFKB Family and Activator protein 1 / Transcription Factor AP-1 (AP-1) activation and the transcription of effectors of the innate immune response .
In addition, the MyD88/IRAK/TRAF6 complex mediates the activation of transcription factors interferon (IFN) regulatory factor 5 (IRF5) and interferon (IFN) regulatory factor 7 (IRF7) for cytokine and Interferon alfa (IFN-alfa) production, respectively.
Ubiquitin-conjugating enzyme 13 (UBC13) and a UBC-like protein UEV1A, both of which facilitate lysine 63 ubiquitination of TNF receptor-associated Factor 6 (TRAF6) .
ECSIT (evolutionary conserved signaling intermediate in Toll pathways) regulates the activity of Transforming growth factor-β-Activated Kinase 1 (TAK1) .
Chen 2005 Nat. Cell. Biol. 7: 758-65
West et al. 2006 Annu Rev Cell Dev Biol. 22: 409-37

see also:
CD284 (Toll-Like Receptor 4 (TLR-4))
Interferons Type I (IFN Type I) & NFKB Signal transduction / NFKB Signal transduction pathway
Myeloid Differentiation Primary Response 88 (MYD88)
MyD88 (Myeloid differentiation primary response 88) signaling
NFKB / TLR4 signal transduction pathway
TRPM7
Toll-like receptor - MyD88 - Signal transduction / Signal transduction pathway
Toll-like receptor signaling pathways