_enti_e7
_enti_e8
_enti_e1
_enti_e9
_enti_e10
_enti_e2
_enti_e4
_enti_e3
_enti_e55
_enti_e53
_enti_e59
_enti_e54
_enti_e50
_enti_e52
_enti_e51
_enti_e56
_enti_e61
_enti_e58
_enti_e57
_enti_e60
_enti_e62
g2_fact_g2
g1_fact_g14
g2_fact_g12
g2_fact_g13
g1_fact_g1
p1_propro_p1
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.
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c33 cso30:c:InputInhibitor connector
c3 cso30:c:OutputProcess connector
p2_propro_p2
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.
c4 cso30:c:InputProcess connector
c5 cso30:c:InputProcess connector
c7 cso30:c:InputProcess connector
c56 cso30:c:InputInhibitor connector
c6 cso30:c:OutputProcess connector
p3_propro_p3
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.
c8 cso30:c:InputProcess connector
c9 cso30:c:InputProcess connector
c10 cso30:c:OutputProcess connector
p4_propro_p4
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.
c11 cso30:c:InputProcess connector
c12 cso30:c:InputProcess connector
c13 cso30:c:OutputProcess connector
p5_propro_p5
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.
c14 cso30:c:InputProcess connector
c58 cso30:c:InputInhibitor connector
c15 cso30:c:OutputProcess connector
p6_propro_p6
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.
c16 cso30:c:InputProcess connector
c59 cso30:c:InputInhibitor connector
c17 cso30:c:OutputProcess connector
p7_propro_p7
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.
c18 cso30:c:InputProcess connector
c20 cso30:c:InputAssociation connector
c35 cso30:c:InputInhibitor connector
c57 cso30:c:InputInhibitor connector
c19 cso30:c:OutputProcess connector
p8_propro_p8
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.
c22 cso30:c:InputAssociation connector
c26 cso30:c:InputAssociation connector
c21 cso30:c:OutputProcess connector
p9_propro_p9
PMID: 16785490
TLR2 and 4 are known to be able to associate with multiple adaptors, including MyD88 and Tirap/Mal.
c23 cso30:c:InputProcess connector
c24 cso30:c:InputProcess connector
c25 cso30:c:OutputProcess connector
p10_propro_p10
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.
c27 cso30:c:InputProcess connector
c28 cso30:c:InputProcess connector
c29 cso30:c:OutputProcess connector
p11_propro_p11
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.
c30 cso30:c:InputProcess connector
c32 cso30:c:InputAssociation connector
c34 cso30:c:InputInhibitor connector
c31 cso30:c:OutputProcess connector
p12_propro_p12
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.
c36 cso30:c:InputProcess connector
c37 cso30:c:InputProcess connector
c38 cso30:c:OutputProcess connector
p13_propro_p13
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.
c42 cso30:c:InputAssociation connector
c40 cso30:c:OutputProcess connector
p14_propro_p14
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.
c44 cso30:c:InputProcess connector
c41 cso30:c:InputProcess connector
c54 cso30:c:InputInhibitor connector
c45 cso30:c:OutputProcess connector
p15_propro_p15
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.
c46 cso30:c:InputProcess connector
c49 cso30:c:InputProcess connector
c55 cso30:c:InputInhibitor connector
c51 cso30:c:OutputProcess connector
p16_propro_p16
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.
c48 cso30:c:InputProcess connector
c47 cso30:c:InputProcess connector
c50 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 16785490, 9806920
Autophosphorylation takes place at the Pelle DD and has been proposed to occur subsequent to Pelle dimerization.
c39 cso30:c:InputProcess connector
c43 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 16785490, 9806920
Autophosphorylation takes place at the Pelle DD and has been proposed to occur subsequent to Pelle dimerization.
c52 cso30:c:InputProcess connector
c53 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 16785490
TLR2 and 4 are known to be able to associate with multiple adaptors, including MyD88 and Tirap/Mal.
c60 cso30:c:InputProcess connector
c61 cso30:c:InputProcess connector
c62 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 16785490
TLR2 and 4 are known to be able to associate with multiple adaptors, including MyD88 and Tirap/Mal.
c63 cso30:c:InputProcess connector
c64 cso30:c:InputProcess connector
c65 cso30:c:OutputProcess connector
p21_propro_p21
PMID: 16785490
TLR2 and 4 are known to be able to associate with multiple adaptors, including MyD88 and Tirap/Mal.
c66 cso30:c:InputProcess connector
c67 cso30:c:InputProcess connector
c68 cso30:c:OutputProcess connector
TLR4_enti_MO000019394
TLR4
TLR2_enti_MO000019397
TLR2
TLR1_enti_MO000019396
TLR1
Ligand: TLR_enti_e6
Ligand: TLR
Ligand: TLR: MyD88_enti_e12
Ligand: TLR: MyD88
Ligand: TLR: MyD88: IRAK-1: IRAK-4_enti_e5
Ligand: TLR: MyD88: IRAK-1: IRAK-4
Ligand: TLR: MyD88: IRAK-1{p}: IRAK-4_enti_e14
Ligand: TLR: MyD88: IRAK-1{p}: IRAK-4
PGN: TLR2: TLR1_enti_e17
PGN: TLR2: TLR1
TLR2: TLR1_enti_e18
TLR2: TLR1
cytokine_enti_e23
cytokine
NF-kappaB_enti_MO000000058
NF-kappaB
MyD88_enti_MO000016573
MyD88
IRAK-1_enti_MO000000213
IRAK-1
IRAK-4_enti_MO000039077
IRAK-4
PGN_enti_MO000042032
PGN
cytokines_enti_MO000019387
cytokines
MAL_enti_MO000068831
MAL
TRAM_enti_MO000041132
TRAM
pelle(d)_enti_MO000016642
pelle(d)
NF-kappaB{activated}_enti_e11
NF-kappaB{activated}
PGN: TLR2: TLR1: MAL_enti_e13
PGN: TLR2: TLR1: MAL
Ligand: TLR: MyD88: IRAK-1{p}: IRAK-4_enti_e15
Ligand: TLR: MyD88: IRAK-1{p}: IRAK-4
A46R_enti_e16
A46R
A46R: MyD88_enti_e19
A46R: MyD88
MAPKs_enti_MO000000077
MAPKs
MAPKs{activated}_enti_e20
MAPKs{activated}
A46R: TLR4_enti_e21
A46R: TLR4
drocomycin_enti_e22
drocomycin
Tube: pelle(d)_enti_e25
Tube: pelle(d)
Tube_enti_e24
Tube
MyD88s_enti_e26
MyD88s
ligand: Toll receptor: MyD88(d)_enti_e27
ligand: Toll receptor: MyD88(d)
ligand: Toll receptor_enti_e28
ligand: Toll receptor
Myd88(d)_enti_MO000091902
Myd88(d)
ligand: Toll receptor: MyD88(d): Tube: pelle(d)_enti_e29
ligand: Toll receptor: MyD88(d): Tube: pelle(d)
pelle: pelle(d)_enti_e30
pelle: pelle(d)
pelle: pelle(d){p}_enti_e31
pelle: pelle(d){p}
PGN: TLR2: TLR1: MAL: MyD88_enti_e32
PGN: TLR2: TLR1: MAL: MyD88
LPS: TLR4_enti_e33
LPS: TLR4
LPS: TLR4: MAL_enti_e34
LPS: TLR4: MAL
LPS: TLR4: MAL: MyD88_enti_e35
LPS: TLR4: MAL: MyD88