PMID: 16785490, 12810098 The TIR domain of the TLR interacts with a set of TIR domain-containing adaptor proteins. PMID: 16785490, 11743586 Drosophila MyD88 (dMyD88) was found to associate directly with the cytoplasmic portion of the Toll receptor and required Tube and Pelle to activate the expression of the antifungal peptide Drosomycin.

PMID: 16785490 In this study, A46R was shown to directly associate with MyD88 and inhibit MyD88 dependent signaling by both IL-1R and TLRs, presumably by interacting via its TIR domain.

PMID: 16785490 In fact, a vaccinia virus immune evasion strategy using a TIR domain-containing viral protein, A46R, targets MyD88, Tirap/Mal, Trif/Ticam, and TRAM and interferes with the downstream activation of MAP kinases and NF-kappaB.

PMID: 16785490 Interestingly, the A46R protein was also able to be immunoprecipitated with TLR4 itself suggesting that the TIR domain of TLR4 might also be a target.

PMID: 16785490, 11743586 Drosophila MyD88 (dMyD88) was found to associate directly with the cytoplasmic portion of the Toll receptor and required Tube and Pelle to activate the expression of the antifungal peptide Drosomycin.

PMID: 16785490, 10589682, 7527496 It is apparent that Tube does bind directly to Pelle both in vivo and in vitro. PMID: 1785490 Pelle is known to autophosphorylate, and this occurrence prevents association with Toll and Tube.

PMID: 16785490 They went on to further show that the DD of Tube is sufficient to mediate the association of full-length dMyD88 and Pelle. PMID: 1785490 Pelle is known to autophosphorylate, and this occurrence prevents association with Toll and Tube.

PMID: 16785490, 11743586 Drosophila MyD88 (dMyD88) was found to associate directly with the cytoplasmic portion of the Toll receptor and required Tube and Pelle to activate the expression of the antifungal peptide Drosomycin.

PMID: 16785490, 9806920 Autophosphorylation takes place at the Pelle DD and has been proposed to occur subsequent to Pelle dimerization.

PMID: 16785490, 9806920 Autophosphorylation takes place at the Pelle DD and has been proposed to occur subsequent to Pelle dimerization.

PMID: 16785490 TLR2 and 4 are known to be able to associate with multiple adaptors, including MyD88 and Tirap/Mal.

PMID: 16785490, 12538665 The universal adaptor protein, MyD88, serves to recruit a family of kinases known as the IL-1R-associated kinases (IRAKs) (2), eventually culminating in the activation of NF-kappaB and the production of proinflammatory cytokines. PMID: 16785490, 12538665 To mediate TLR/IL-1R signaling, IRAK-4 associates with the intermediate domain (ID) of the adaptor MyD88 presumably via its own DD. PMID: 16785490 IRAK-1, on the other hand, associates with the DD of MyD88 effectively poised for phosphorylation by IRAK-4. IRAK-1, on the other hand, associates with the DD of MyD88 effectively poised for phosphorylation by IRAK-4. PMID: 16785490, 12538665 A splice variant of MyD88 (MyD88s), missing the intermediate domain, has been shown to shut down IL-1/LPS-induced NF-kappaB activation by interfering with IRAK-4 association.

PMID: 16785490 TLR2 and 4 are known to be able to associate with multiple adaptors, including MyD88 and Tirap/Mal.

PMID: 16785490 TLR2 and 4 are known to be able to associate with multiple adaptors, including MyD88 and Tirap/Mal.

PMID: 16785490, 12437972 In addition to the importance of maintaining the structural integrity of the bb and dd loops, it has also been proposed that dimerization of the TLR2 TIR domain is vital for downstream signaling to occur.

PMID: 16785490, 12437972 In addition to the importance of maintaining the structural integrity of the bb and dd loops, it has also been proposed that dimerization of the TLR2 TIR domain is vital for downstream signaling to occur.

PMID: 16785490 IRAK-4 is a unique member of the IRAK family in that it is the only member to have true kinase activity (i.e., phosphorylates substrates other than itself) and it is also the most homologous to Pelle. PMID: 16785490 IRAK-1, on the other hand, associates with the DD of MyD88 effectively poised for phosphorylation by IRAK-4. IRAK-1, on the other hand, associates with the DD of MyD88 effectively poised for phosphorylation by IRAK-4. PMID: 16785490 This phosphorylation most likely takes place on the activation loop of IRAK-1 (within the kinase domain) on residues T387 and S376. PMID: 16785490, 9261174 Also, in the presence of MyD88s, IRAK-1 is not phosphorylated or subsequently ubiquitinated as in the normal signaling cascade.

PMID: 16785490, 11960013, 11937546, 11287640 Once this phosphorylation event occurs, IRAK-1 kinase activity increases and it heavily autophosphorylates residues in its amino terminus. PMID: 16785490, 9261174 Also, in the presence of MyD88s, IRAK-1 is not phosphorylated or subsequently ubiquitinated as in the normal signaling cascade.

PMID: 16785490, 12538665 The universal adaptor protein, MyD88, serves to recruit a family of kinases known as the IL-1R-associated kinases (IRAKs) (2), eventually culminating in the activation of NF-kappaB and the production of proinflammatory cytokines. PMID: 16785490 In fact, a vaccinia virus immune evasion strategy using a TIR domain-containing viral protein, A46R, targets MyD88, Tirap/Mal, Trif/Ticam, and TRAM and interferes with the downstream activation of MAP kinases and NF-kappaB. PMID: 16785490, 12538665 A splice variant of MyD88 (MyD88s), missing the intermediate domain, has been shown to shut down IL-1/LPS-induced NF-kappaB activation by interfering with IRAK-4 association.

PMID: 16785490, 12538665 The universal adaptor protein, MyD88, serves to recruit a family of kinases known as the IL-1R-associated kinases (IRAKs) (2), eventually culminating in the activation of NF-kappaB and the production of proinflammatory cytokines.

PMID: 16785490 TLR2 and 4 are known to be able to associate with multiple adaptors, including MyD88 and Tirap/Mal.