PMID: 14609719
MD-2, a small protein that lacks a transmembrane domain, is identified to associate with the extracellular domain of TLR4.PMID: 14609719
CD14 concentrates LPS and presents it to TLR4-MD-2.
TLR4, MD-2 and CD11b/CD18 are recruited to the rafts, thereby triggering multiple signaling cascades (i.e., activation of NF-κB and MAPK).PMID: 14609719
The TIR domain of MyD88 associates with the TIR domain of TLR and IL-1 receptor.PMID: 14609719
IRAKs are subsequently phosphorylated and are dissociated from the receptor complex.
IRAKs associate receptor complex transiently.(Fig3)PMID: 14609719, 9625770, 8599092
IRAKs are subsequently phosphorylated and are dissociated from the receptor complex and interact with another adaptor molecule, TRAF6. PMID: 14609719
TRAF6 activates MAPK kinases.indirectPMID: 14609719
TRAF6 activates MAPK kinases,which can lead to AP-1 activation through MAPK. PMID: 14609719
TRAF6 activates the inhibitors of κB (IκB) kinase (IKK) complex.PMID: 14609719
The IKK complex is composed of 2 catalytic subunits IKKα and IKKβ and one regulatory subunit IKKγ and induces phosphorylation of IκB.PMID: 14609719
The phosphorylation of the IκBs results in their polyubiquitination, which in turn leads to their 26S proteasome-mediated degradation.PMID: 14609719
The phosphorylation of the IκBs results in their polyubiquitination, which in turn leads to their 26S proteasome-mediated degradation.PMID: 14609719
NF-κB translocates into the nucleus.indirectPMID: 14609719
NF-κappaB translocate into the nucleus and activate the transcription of many κB-dependent genes, including TNF-α and IκBα.indirectPMID: 14609719
NF-κappaB translocate into the nucleus and activate the transcription of many κB-dependent genes, including TNF-α and IκBα.PMID: 14609719
TIRAP/Mal binds directly to TLR4.
PMID: 14609719,12447441
TIRAP-deficient mice have similar LPS-responsive phenotypes to MyD88-deficient mice with regard to the MyD88-independent pathway.indirectPMID: 14609719
Activation of TLR4 by LPS also induces the phosphorylation and nuclear translocation of IRF3.PMID: 14609719
Activation of TLR4 by LPS also induces the phosphorylation and nuclear translocation of IRF3.indirectPMID: 14609719
Activation of TLR4 by LPS induces the phosphorylation and nuclear translocation of IRF3, which causes up-regulation of a set of genes, including IFN-β.PMID: 14609719
Phosphorylated IRAK-1 first binds TRAF6, resulting in the activation of NF-κB. The phosphorylated IRAK-1 is then degraded in an ubiquitination-dependent pathway.PMID: 14609719
Phosphorylated IRAK-1 first binds TRAF6, resulting in the activation of NF-κB. The phosphorylated IRAK-1 is then degraded in an ubiquitination-dependent pathway.PMID: 14609719
LBP transfers LPS to membrane CD14, and the intercalated LPS is released in lipid membrane; subsequently,the intercalated LPS binds to a complex of receptors composed of chemokine receptor 4, growth differentiation factor 5, and heat shock proteins 70 and 90 in lipid rafts.PMID: 14609719, 12791997
Nod1 specifically detects a diaminopimelate-containing N-acetylglucosamine-N-acetylmuramic acid tripeptide motif of peptidoglycan found in Gram-negative bacteria.PMID: 14609719,11894097
Nod1 activates NF-κB through its association with the receptor-interacting protein 2 (Rip2), a CARD-containing serine/threonine kinase that directly interacts with IKKγ, the regulatory subunit of the IKK complex.PMID: 14609719
Dimers of MyD88 bind IRAK-1and IRAK-4 bringing the respective domains in close association,resulting in the phosphorylation of IRAK-1 by IRAK-4, which may induce the kinase activity of IRAK-1 leading to its autophosphorylation.PMID: 14609719
Dimers of MyD88 bind IRAK-1and IRAK-4 bringing the respective domains in close association,resulting in the phosphorylation of IRAK-1 by IRAK-4, which may induce the kinase activity of IRAK-1 leading to its autophosphorylation.PMID: 14609719
Dimers of MyD88 bind IRAK-1and IRAK-4 bringing the respective domains in close association,resulting in the phosphorylation of IRAK-1 by IRAK-4, which may induce the kinase activity of IRAK-1 leading to its autophosphorylation.PMID: 1469719
The IKK complex is composed of 2 catalytic subunits IKKa and IKKb and one regulatory subunit IKKg and induces phosphorylation of IkappaB.
PMID: 1469719,11894097
Nod1 activates NF-kB through its association with the receptor-interacting protein 2 (Rip2), a CARD-containing serine/threonine kinase that directly interacts with IKKg, the regulatory subunit of the IKK complex. Studies using Rip2-deficient cells have demonstrated that Rip2 is essential for the activation of NF-kB by Nod1 and Nod2.PMID: 1469719,11894097
Nod1 activates NF-kB through its association with the receptor-interacting protein 2 (Rip2), a CARD-containing serine/threonine kinase that directly interacts with IKKg, the regulatory subunit of the IKK complex. Studies using Rip2-deficient cells have demonstrated that Rip2 is essential for the activation of NF-kB by Nod1 and Nod2.