_enti_e7
_enti_e8
_enti_e9
_enti_e1
_enti_e10
_enti_e3
_enti_e2
_enti_e4
_enti_e55
_enti_e20
_enti_e59
_enti_e53
_enti_e19
_enti_e18
_enti_e51
_enti_e54
_enti_e50
_enti_e52
_enti_e56
_enti_e57
_enti_e58
_enti_e61
_enti_e60
_enti_e62
g1_fact_g1
g1_fact_g14
g2_fact_g12
g2_fact_g13
g1_fact_g2
p1_propro_p1
PMID: 17667936,12763684
There are also a number of ligands such as lipoteichoic acid and mycobacterial lipoarabinomannan that appear to be recognized by TLR2 independent of TLR1 or TLR6
c4 cso30:c:InputProcess connector
c5 cso30:c:InputProcess connector
c6 cso30:c:OutputProcess connector
c15 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 17667936,11095740,15795223,16720699
TLR2 is known to form heterodimers with TLR1 or TLR6 while TLR4 homodimerizes in a similar fashion to dToll
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 17667936,12077222
While the TLR2/TLR6 heterodimer detects diacylated lipoproteins from bacteria, the TLR2/TLR1 heterodimer senses triacylated lipoproteins.
PMID: 17667936,15690042
CD14 has also been shown to be required for signalling induced by TLR2 ligands,and it has been found recently that the scavenger receptor CD36 is involved in recognition of diacylated lipopeptides by TLR2/6 heterodimers.
c7 cso30:c:InputProcess connector
c8 cso30:c:InputProcess connector
c43 cso30:c:InputAssociation connector
c9 cso30:c:OutputProcess connector
p3_propro_p4
PMID: 17667936,12077222
While the TLR2/TLR6 heterodimer detects diacylated lipoproteins from bacteria, the TLR2/TLR1 heterodimer senses triacylated lipoproteins.
c10 cso30:c:InputProcess connector
c11 cso30:c:InputProcess connector
c12 cso30:c:OutputProcess connector
p5_propro_p5
c13 cso30:c:InputProcess connector
c14 cso30:c:InputProcess connector
p6_propro_p6
PMID: 17667936
TLR3 detects the double-stranded RNA (dsRNA) from viruses.
c16 cso30:c:InputProcess connector
c17 cso30:c:InputProcess connector
c18 cso30:c:OutputProcess connector
p7_propro_p7
PMID: 17667936
TLR5 senses flagellin, a highly conserved component of bacterial flagella.
c19 cso30:c:InputProcess connector
c20 cso30:c:InputProcess connector
c21 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 17667936
Both TLR7 and TLR8 recognize the single-stranded RNA (ssRNA) from viruses, while TLR9 is responsible for detecting bacterial and viral CpG DNA motifs.
c22 cso30:c:InputProcess connector
c23 cso30:c:InputProcess connector
c24 cso30:c:OutputProcess connector
p8_propro_p9
PMID: 17667936
Both TLR7 and TLR8 recognize the single-stranded RNA (ssRNA) from viruses, while TLR9 is responsible for detecting bacterial and viral CpG DNA motifs.
c25 cso30:c:InputProcess connector
c26 cso30:c:InputProcess connector
c27 cso30:c:OutputProcess connector
p8_propro_p10
PMID: 17667936
Both TLR7 and TLR8 recognize the single-stranded RNA (ssRNA) from viruses, while TLR9 is responsible for detecting bacterial and viral CpG DNA motifs.
c28 cso30:c:InputProcess connector
c29 cso30:c:InputProcess connector
c30 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 17667936,15010525,15895089
It seems that an LPS response requires the sequential interaction and transfer of LPS to LPS-binding protein, the glycosylphosphatidylinositol-anchored protein CD14 and MD-2, and the simultaneous engagement of LPS and TLR4 by MD-2
c31 cso30:c:InputProcess connector
c32 cso30:c:InputProcess connector
c33 cso30:c:OutputProcess connector
p11_propro_p12
PMID: 17667936,15010525,15895089
It seems that an LPS response requires the sequential interaction and transfer of LPS to LPS-binding protein, the glycosylphosphatidylinositol-anchored protein CD14 and MD-2, and the simultaneous engagement of LPS and TLR4 by MD-2
c34 cso30:c:InputProcess connector
c35 cso30:c:InputProcess connector
c36 cso30:c:OutputProcess connector
p11_propro_p13
PMID: 17667936,15010525,15895089
It seems that an LPS response requires the sequential interaction and transfer of LPS to LPS-binding protein, the glycosylphosphatidylinositol-anchored protein CD14 and MD-2, and the simultaneous engagement of LPS and TLR4 by MD-2
c37 cso30:c:InputProcess connector
c38 cso30:c:InputProcess connector
c39 cso30:c:OutputProcess connector
p11_propro_p14
PMID: 17667936,15010525,15895089
It seems that an LPS response requires the sequential interaction and transfer of LPS to LPS-binding protein, the glycosylphosphatidylinositol-anchored protein CD14 and MD-2, and the simultaneous engagement of LPS and TLR4 by MD-2
c40 cso30:c:InputProcess connector
c41 cso30:c:InputProcess connector
c42 cso30:c:OutputProcess connector
p15_propro_p15
PMID: 17667936
MyD88 is recruited to the cytoplasmic portion of the TLR and interacts with IRAK4 and IRAK1 via homophilic DD interactions.
PMID: 17667936
Mal recruits MyD88, which binds IRAK4 and -1.
c44 cso30:c:InputProcess connector
c45 cso30:c:InputProcess connector
c46 cso30:c:OutputProcess connector
p16_propro_p16
PMID: 17667936
MyD88 is recruited to the cytoplasmic portion of the TLR and interacts with IRAK4 and IRAK1 via homophilic DD interactions.
c47 cso30:c:InputProcess connector
c48 cso30:c:InputProcess connector
c49 cso30:c:InputProcess connector
c50 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 17667936,11518704,9430229,12538665,12885415,11960013
17362201
Activated IRAK4 phosphorylates and activates IRAK1 which subsequently interacts with TNFR-associated factor-6 (TRAF6),causing the oligomerization and activation of TRAF6.
c51 cso30:c:InputProcess connector
c52 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 17667936,11518704,9430229,12538665,12885415,11960013
17362201
Activated IRAK4 phosphorylates and activates IRAK1 which subsequently interacts with TNFR-associated factor-6 (TRAF6),causing the oligomerization and activation of TRAF6.
c53 cso30:c:InputProcess connector
c54 cso30:c:InputProcess connector
c55 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 17667936,11518704,9430229,12538665,12885415,11960013
17362201
Activated IRAK4 phosphorylates and activates IRAK1 which subsequently interacts with TNFR-associated factor-6 (TRAF6),causing the oligomerization and activation of TRAF6.
c56 cso30:c:InputProcess connector
c57 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 17667936,16056267,11057907
TRAF6 is a ubiquitin E3 ligase and functions with the ubiquitin-conjugating enzyme Ubc13 and the Ubc-like protein Uev1a to catalyze the synthesis of Lys63-linked polyubiquitin chains on target proteins including TRAF6 itself.
c58 cso30:c:InputProcess connector
c59 cso30:c:InputAssociation connector
c60 cso30:c:InputAssociation connector
c61 cso30:c:OutputProcess connector
p21_propro_p21
PMID: 17667936,16056267,11057907,10882101
Ubiquitinated TRAF6 then recruits TAB2 and activates the TAB2-associated TAK1 kinase
c62 cso30:c:InputProcess connector
c63 cso30:c:InputProcess connector
c64 cso30:c:OutputProcess connector
p22_propro_p22
PMID: 17667936,16056267,11057907,10882101
Ubiquitinated TRAF6 then recruits TAB2 and activates the TAB2-associated TAK1 kinase
c65 cso30:c:InputProcess connector
c66 cso30:c:OutputProcess connector
p23_propro_p23
PMID: 17667936
Activated TAK1 then activates the IKK complex which phosphorylates IkappaB resulting in its ubiquitination and subsequent proteosome-mediated degradation.
c67 cso30:c:InputAssociation connector
c68 cso30:c:InputProcess connector
c69 cso30:c:OutputProcess connector
p24_propro_p24
c70 cso30:c:InputAssociation connector
c71 cso30:c:InputProcess connector
c72 cso30:c:OutputProcess connector
p25_propro_p25
c73 cso30:c:InputProcess connector
c74 cso30:c:OutputProcess connector
p26_propro_p26
PMID: 17667936
Activated TAK1 then activates the IKK complex which phosphorylates IkappaB resulting in its ubiquitination and subsequent proteosome-mediated degradation.
PMID: 17667936,15371334,11460167
This leaves NF-kappaB free to translocate to the nucleus and initiate gene transcription
c75 cso30:c:InputProcess connector
c76 cso30:c:OutputProcess connector
c77 cso30:c:OutputProcess connector
p27_propro_p27
PMID: 17667936,15371334,11460167
This leaves NF-kappaB free to translocate to the nucleus and initiate gene transcription
c78 cso30:c:InputProcess connector
c79 cso30:c:OutputProcess connector
p28_propro_p28
PMID: 17667936,15371334,11460167
This leaves NF-kappaB free to translocate to the nucleus and initiate gene transcription
c80 cso30:c:InputAssociation connector
c81 cso30:c:OutputProcess connector
p29_propro_p29
PMID: : 17667936,11460167
TAK1 is also responsible for the activation of MKK6 which phosphorylates and activates the kinases JNK and P38 and thereby mediates AP-1 activation
c82 cso30:c:InputAssociation connector
c83 cso30:c:InputProcess connector
c84 cso30:c:OutputProcess connector
p30_propro_p30
PMID: : 17667936,11460167
TAK1 is also responsible for the activation of MKK6 which phosphorylates and activates the kinases JNK and P38 and thereby mediates AP-1 activation
c85 cso30:c:InputAssociation connector
c86 cso30:c:InputProcess connector
c87 cso30:c:OutputProcess connector
p30_propro_p31
PMID: : 17667936,11460167
TAK1 is also responsible for the activation of MKK6 which phosphorylates and activates the kinases JNK and P38 and thereby mediates AP-1 activation
c88 cso30:c:InputAssociation connector
c89 cso30:c:InputProcess connector
c90 cso30:c:OutputProcess connector
p32_propro_p32
PMID: : 17667936,11460167
TAK1 is also responsible for the activation of MKK6 which phosphorylates and activates the kinases JNK and P38 and thereby mediates AP-1 activation
c91 cso30:c:InputAssociation connector
c92 cso30:c:InputProcess connector
c93 cso30:c:OutputProcess connector
p32_propro_p33
PMID: : 17667936,11460167
TAK1 is also responsible for the activation of MKK6 which phosphorylates and activates the kinases JNK and P38 and thereby mediates AP-1 activation
c94 cso30:c:InputAssociation connector
c95 cso30:c:InputProcess connector
c96 cso30:c:OutputProcess connector
p34_propro_p34
PMID: 17667936,15361868,15492225,15767370
Upon ligand binding to TLR 7, 8 or 9, IRF7 is recruited to a complex containing MyD88, TRAF6, IRAK4 and IRAK1.
c97 cso30:c:InputProcess connector
c98 cso30:c:InputProcess connector
c99 cso30:c:OutputProcess connector
p34_propro_p35
PMID: 17667936,15361868,15492225,15767370
Upon ligand binding to TLR 7, 8 or 9, IRF7 is recruited to a complex containing MyD88, TRAF6, IRAK4 and IRAK1.
c104 cso30:c:InputProcess connector
c108 cso30:c:InputProcess connector
c109 cso30:c:OutputProcess connector
p36_propro_p36
PMID: 17667936
Phosphorylation of IRF7 by IRAK1 in this complex was found to be essential for its transcriptional activation.
c110 cso30:c:InputProcess connector
c111 cso30:c:OutputProcess connector
p37_propro_p37
PMID: 17667936
This results in the activation of IRF7 which translocates to the nucleus to produce IFN-alpha and IFN-inducible genes.
c105 cso30:c:InputProcess connector
c106 cso30:c:OutputProcess connector
c107 cso30:c:OutputProcess connector
c112 cso30:c:OutputProcess connector
p38_propro_p38
PMID: 17667936
Figure 1
c100 cso30:c:InputProcess connector
c101 cso30:c:OutputProcess connector
p39_propro_p39
PMID: 17667936
Figure 1
c102 cso30:c:InputProcess connector
c103 cso30:c:OutputProcess connector
p40_propro_p40
PMID: 17667936
This results in the activation of IRF7 which translocates to the nucleus to produce IFN-alpha and IFN-inducible genes.
c113 cso30:c:InputAssociation connector
c114 cso30:c:OutputProcess connector
p40_propro_p41
PMID: 17667936
This results in the activation of IRF7 which translocates to the nucleus to produce IFN-alpha and IFN-inducible genes.
c115 cso30:c:InputAssociation connector
c116 cso30:c:OutputProcess connector
p42_propro_p42
PMID: 17667936
TRAF6 can also activate IRF5.
c117 cso30:c:InputAssociation connector
c118 cso30:c:InputProcess connector
c119 cso30:c:OutputProcess connector
p43_propro_p43
PMID: 17667936,15665823
It was shown that IRF5 interacts with, and is activated by MyD88 and TRAF6 causing the nuclear translocation of IRF5 and the expression of inflammatory cytokines.
c120 cso30:c:InputProcess connector
c121 cso30:c:OutputProcess connector
p44_propro_p44
c122 cso30:c:InputAssociation connector
c123 cso30:c:OutputProcess connector
p45_propro_p45
PMID: 17667936,17018642
Upon TLR activation, IRF1 is activated by MyD88, causing it to translocate to the nucleus where it induces a specific gene subset including IFN-beta, inducible NO synthase and IL-12p35
c124 cso30:c:InputAssociation connector
c125 cso30:c:InputProcess connector
c126 cso30:c:OutputProcess connector
p46_propro_p46
c127 cso30:c:InputProcess connector
c128 cso30:c:OutputProcess connector
p47_propro_p47
PMID: 17667936,17018642
Upon TLR activation, IRF1 is activated by MyD88, causing it to translocate to the nucleus where it induces a specific gene subset including IFN-beta, inducible NO synthase and IL-12p35
c129 cso30:c:InputAssociation connector
c130 cso30:c:OutputProcess connector
p47_propro_p48
PMID: 17667936,17018642
Upon TLR activation, IRF1 is activated by MyD88, causing it to translocate to the nucleus where it induces a specific gene subset including IFN-beta, inducible NO synthase and IL-12p35
c131 cso30:c:InputAssociation connector
c132 cso30:c:OutputProcess connector
p47_propro_p49
PMID: 17667936,17018642
Upon TLR activation, IRF1 is activated by MyD88, causing it to translocate to the nucleus where it induces a specific gene subset including IFN-beta, inducible NO synthase and IL-12p35
c133 cso30:c:InputAssociation connector
c134 cso30:c:OutputProcess connector
p50_propro_p50
PMID: 17667936
It is initiated in the case of TLR4 by the TIR domain of Mal binding the TIR domain of TLR4, which has dimerized after ligand binding.
c136 cso30:c:InputProcess connector
c138 cso30:c:InputProcess connector
c137 cso30:c:OutputProcess connector
p51_propro_p51
PMID: 17667936
It is initiated in the case of TLR4 by the TIR domain of Mal binding the TIR domain of TLR4, which has dimerized after ligand binding.
c135 cso30:c:InputProcess connector
c169 cso30:c:OutputProcess connector
p52_propro_p52
PMID: 17667936
Figure 1
PMID: 17667936,14679297,14530355
TRIF mediates IRF3 activation via TRAF family member-associated NF-kappaB activator (TANK)-binding kinase 1 (TBK1), which associates with the N terminus of TRIF
c139 cso30:c:InputProcess connector
c140 cso30:c:InputProcess connector
c141 cso30:c:OutputProcess connector
p52_propro_p53
PMID: 17667936
Figure 1
PMID: 17667936,14679297,14530355
TRIF mediates IRF3 activation via TRAF family member-associated NF-kappaB activator (TANK)-binding kinase 1 (TBK1), which associates with the N terminus of TRIF
c142 cso30:c:InputProcess connector
c143 cso30:c:InputProcess connector
c144 cso30:c:OutputProcess connector
p54_propro_p54
c145 cso30:c:InputProcess connector
c146 cso30:c:InputProcess connector
c147 cso30:c:OutputProcess connector
p56_propro_p56
PMID: 17667936
Figure 1
c149 cso30:c:InputProcess connector
c156 cso30:c:InputAssociation connector
c150 cso30:c:OutputProcess connector
p57_propro_p57
PMID: 17667936
Figure 1
c151 cso30:c:InputProcess connector
c152 cso30:c:OutputProcess connector
p58_propro_p58
PMID: 17667936
Figure 1
c153 cso30:c:InputAssociation connector
c154 cso30:c:OutputProcess connector
p59_propro_p59
PMID: 17667936,16306937,16306936,15611223
Recently, both TRAF3 and NAK-associated protein 1 (NAP1) have been implicated in mediating the activation of TBK1 by TRIF by acting as a bridge between the two proteins
c148 cso30:c:InputProcess connector
c157 cso30:c:InputAssociation connector
c158 cso30:c:InputAssociation connector
c155 cso30:c:OutputProcess connector
p60_propro_p60
PMID: 17667936,15064760
TRIF also associates with receptor-interacting protein 1 (RIP1) via its C-terminal RIP homotypic interaction motif (RHIM), and in the absence of RIP1, TLR3-mediated NF-kappaB activation was abolished, suggesting that RIP1 mediates the TRIF-induced NF-kappaB activation
c159 cso30:c:InputProcess connector
c160 cso30:c:InputProcess connector
c161 cso30:c:OutputProcess connector
p61_propro_p61
PMID: 17667936
Alternatively RIP1 is activated by TRIF and this feeds into the MyD88 pathway by activating TRAF6.
c162 cso30:c:InputAssociation connector
c163 cso30:c:InputProcess connector
c164 cso30:c:OutputProcess connector
p61_propro_p62
PMID: 17667936
Figure 1
c165 cso30:c:InputAssociation connector
c166 cso30:c:InputProcess connector
c167 cso30:c:OutputProcess connector
p55_propro_p55
PMID: 17667936,14517278
It functions as a bridging adaptor for the MyD88-independent signalling pathway, serving to recruit TRIF to TLR4
c168 cso30:c:InputProcess connector
c170 cso30:c:InputProcess connector
c171 cso30:c:OutputProcess connector
p55_propro_p63
PMID: 17667936,14517278
It functions as a bridging adaptor for the MyD88-independent signalling pathway, serving to recruit TRIF to TLR4
c172 cso30:c:InputProcess connector
c173 cso30:c:InputProcess connector
c174 cso30:c:OutputProcess connector
p64_propro_p64
PMID: 17667936
Figure 1
c175 cso30:c:InputProcess connector
c176 cso30:c:InputProcess connector
c177 cso30:c:OutputProcess connector
p65_propro_p65
PMID: 17667936
Figure 1
c184 cso30:c:InputAssociation connector
c185 cso30:c:InputProcess connector
c186 cso30:c:OutputProcess connector
p61_propro_p66
PMID: 17667936
Alternatively RIP1 is activated by TRIF and this feeds into the MyD88 pathway by activating TRAF6.
c178 cso30:c:InputAssociation connector
c179 cso30:c:InputProcess connector
c180 cso30:c:OutputProcess connector
p61_propro_p67
PMID: 17667936
Figure 1
c181 cso30:c:InputAssociation connector
c182 cso30:c:InputProcess connector
c183 cso30:c:OutputProcess connector
p65_propro_p68
PMID: 17667936
Figure 1
c187 cso30:c:InputAssociation connector
c188 cso30:c:InputProcess connector
c189 cso30:c:OutputProcess connector
p65_propro_p69
PMID: 17667936
Figure 1
c190 cso30:c:InputAssociation connector
c191 cso30:c:InputProcess connector
c192 cso30:c:OutputProcess connector
p70_propro_p70
PMID: 17667936
It was found that TRAM was phosphorylated on serine-16 by PKCalt epsilon upon LPS stimulation
PMID: 17667936
Figure 2
c193 cso30:c:InputProcess connector
c195 cso30:c:InputAssociation connector
c194 cso30:c:OutputProcess connector
p71_propro_p71
PMID: 17667936
The TIR domain of TRIF was involved in the interaction with the TRAF-C domain of TRAF1, and inhibition most likely occurs through sequestration of the TIR domain.
c196 cso30:c:InputProcess connector
c197 cso30:c:InputProcess connector
c198 cso30:c:OutputProcess connector
p72_propro_p72
PMID: 17667936
SARM associates with TRIF and blocks TRIF-induced NF-kappaB activation.
c199 cso30:c:InputProcess connector
c200 cso30:c:InputProcess connector
c201 cso30:c:OutputProcess connector
p73_propro_p73
PMID: 17667936
SARM associates with TRIF and blocks TRIF-induced NF-kappaB activation.
c202 cso30:c:InputAssociation connector
c203 cso30:c:InputProcess connector
c205 cso30:c:InputInhibitor connector
c204 cso30:c:OutputProcess connector
p73_propro_p74
PMID: 17667936
SARM associates with TRIF and blocks TRIF-induced NF-kappaB activation.
PMID: 17667936
It was found that the membrane bound form of ST2, which contains a TIR domain, specifically inhibited NF-kappaB activation downstream of IL-1R, TLR2, TLR4 and TLR9 but not TLR3.
c206 cso30:c:InputAssociation connector
c207 cso30:c:InputProcess connector
c212 cso30:c:InputInhibitor connector
c226 cso30:c:InputInhibitor connector
c208 cso30:c:OutputProcess connector
p72_propro_p75
PMID: 17667936
SARM associates with TRIF and blocks TRIF-induced NF-kappaB activation.
c209 cso30:c:InputProcess connector
c210 cso30:c:InputProcess connector
c211 cso30:c:OutputProcess connector
p76_propro_p76
PMID: 17667936
Transforming growth factor-beta (TGF-beta) partly exerts its anti-inflammatory effects by causing direct ubiquitination of MyD88, thereby augmenting its degradation by the proteasome.
c213 cso30:c:InputAssociation connector
c214 cso30:c:InputProcess connector
c215 cso30:c:OutputProcess connector
p77_propro_p77
PMID: 17667936
Transforming growth factor-beta (TGF-beta) partly exerts its anti-inflammatory effects by causing direct ubiquitination of MyD88, thereby augmenting its degradation by the proteasome.
c216 cso30:c:InputProcess connector
c217 cso30:c:OutputProcess connector
p78_propro_p78
PMID: 17667936
It was found that the membrane bound form of ST2, which contains a TIR domain, specifically inhibited NF-kappaB activation downstream of IL-1R, TLR2, TLR4 and TLR9 but not TLR3.
c218 cso30:c:InputAssociation connector
c219 cso30:c:InputProcess connector
c221 cso30:c:InputInhibitor connector
c220 cso30:c:OutputProcess connector
p78_propro_p79
PMID: 17667936
It was found that the membrane bound form of ST2, which contains a TIR domain, specifically inhibited NF-kappaB activation downstream of IL-1R, TLR2, TLR4 and TLR9 but not TLR3.
c222 cso30:c:InputAssociation connector
c223 cso30:c:InputProcess connector
c225 cso30:c:InputInhibitor connector
c224 cso30:c:OutputProcess connector
p78_propro_p80
PMID: 17667936
It was found that the membrane bound form of ST2, which contains a TIR domain, specifically inhibited NF-kappaB activation downstream of IL-1R, TLR2, TLR4 and TLR9 but not TLR3.
c227 cso30:c:InputAssociation connector
c228 cso30:c:InputProcess connector
c230 cso30:c:InputInhibitor connector
c229 cso30:c:OutputProcess connector
p81_propro_p81
PMID: 17667936
Indeed, Mal could associate with TRAF6 in a co-immunoprecipitation assay.
c231 cso30:c:InputProcess connector
c232 cso30:c:InputProcess connector
c233 cso30:c:OutputProcess connector
p82_propro_p82
PMID: 17667936
It was also shown that Mal is phosphorylated by Bruton's tyrosine kinase (Btk) on tyrosine residues at positions 86 and 187, and this event is necessary for efficient TLR4 signalling.
c234 cso30:c:InputAssociation connector
c235 cso30:c:InputProcess connector
c236 cso30:c:OutputProcess connector
p83_propro_p83
PMID: 17667936
A prerequisite for Mal degradation is tyrosine phosphorylation of Mal by Btk as this may allow SOCS1 to associate with Mal through its SH2 domain.
c237 cso30:c:InputProcess connector
c238 cso30:c:InputProcess connector
c239 cso30:c:OutputProcess connector
p84_propro_p84
PMID: 17667936
Here it was shown that SOCS1 mediates polyubiquitination of Mal on two N-terminal lysine residues, thereby mediating Mal degradation via the 26S proteasome.
c240 cso30:c:InputProcess connector
c241 cso30:c:OutputProcess connector
p85_propro_p85
PMID: 17667936
Here it was shown that SOCS1 mediates polyubiquitination of Mal on two N-terminal lysine residues, thereby mediating Mal degradation via the 26S proteasome.
c242 cso30:c:InputProcess connector
c243 cso30:c:OutputProcess connector
c244 cso30:c:OutputProcess connector
p86_propro_p86
PMID: 17667936
It was also recently found that Mal is cleaved by caspase-1.
c245 cso30:c:InputAssociation connector
c246 cso30:c:InputProcess connector
c247 cso30:c:OutputProcess connector
p87_propro_p87
PMID: 17667936,17161867
In addition, Mal was shown to interact via its TIR domain with protein kinase C-delta (PKCdelta)
c248 cso30:c:InputProcess connector
c249 cso30:c:InputProcess connector
c250 cso30:c:OutputProcess connector
diacylated lipoproteins_enti_e5
diacylated lipoproteins
TLR2_enti_MO000019397
TLR2
TLR1_enti_MO000019396
TLR1
TLR2:TLR1_enti_e6
TLR2:TLR1
TLR2_enti_e11
TLR2
TLR2:TLR6_enti_e12
TLR2:TLR6
TLR2:TLR6:Diacylated lipoproteins_enti_e13
TLR2:TLR6:Diacylated lipoproteins
triacylated lipoproteins_enti_e14
triacylated lipoproteins
TLR2:TLR1:triacylated proteins_enti_e15
TLR2:TLR1:triacylated proteins
Lipoteichoic acid_enti_e16
Lipoteichoic acid
TLR2:Lipoteichoic acid_enti_e17
TLR2:Lipoteichoic acid
TLR3_enti_e21
TLR3
dsRNA_enti_e22
dsRNA
dsRNA:TLR3_enti_e23
dsRNA:TLR3
TLR4_enti_e24
TLR4
LPS_enti_e25
LPS
TLR5_enti_e26
TLR5
Flagellin_enti_e27
Flagellin
TLR5:Flagellin_enti_e28
TLR5:Flagellin
TLR7_enti_e29
TLR7
ssRNA_enti_e30
ssRNA
TLR7:ssRNA_enti_e31
TLR7:ssRNA
TLR8_enti_e32
TLR8
TLR8:ssRNA_enti_e33
TLR8:ssRNA
TLR9_enti_e34
TLR9
CpG DNA_enti_e35
CpG DNA
TLR9:CpG DNA_enti_e36
TLR9:CpG DNA
LBP_enti_e37
LBP
LPS:LBP_enti_e38
LPS:LBP
CD14_enti_e39
CD14
LPS:LBP:CD14_enti_e40
LPS:LBP:CD14
MD-2_enti_e41
MD-2
TLR4:MD-2_enti_e42
TLR4:MD-2
TLR4:MD-2:LPS:LBP:CD14_enti_e43
TLR4:MD-2:LPS:LBP:CD14
CD36_enti_e44
CD36
MyD88_enti_e45
MyD88
TLR4:MD-2:LPS:LBP:CD14:MyD88_enti_e46
TLR4:MD-2:LPS:LBP:CD14:MyD88
IRAK-4_enti_e47
IRAK-4
IRAK-1_enti_e48
IRAK-1
TLR4:MD-2:LPS:LBP:CD14:MyD88:IRAK-4:IRAK-1_enti_e49
TLR4:MD-2:LPS:LBP:CD14:MyD88:IRAK-4:IRAK-1
TLR4:MD-2:LPS:LBP:CD14:MyD88:IRAK-4:IRAK-1{p}_enti_e63
TLR4:MD-2:LPS:LBP:CD14:MyD88:IRAK-4:IRAK-1{p}
TRAF6_enti_MO000000212
TRAF6
TLR4:MD-2:LPS:LBP:CD14:MyD88:IRAK-4:IRAK-1{p}:TRAF6_enti_e64
TLR4:MD-2:LPS:LBP:CD14:MyD88:IRAK-4:IRAK-1{p}:TRAF6
TLR4:MD-2:LPS:LBP:CD14:MyD88:IRAK-4:IRAK-1{p}:TRAF6 oligomer_enti_e65
TLR4:MD-2:LPS:LBP:CD14:MyD88:IRAK-4:IRAK-1{p}:TRAF6 oligomer
Ubc13_enti_MO000022136
Ubc13
Uev1a_enti_e66
Uev1a
TLR4:MD-2:LPS:LBP:CD14:MyD88:IRAK-4:IRAK-1{p}:TRAF6 oligomer{ub}_enti_e67
TLR4:MD-2:LPS:LBP:CD14:MyD88:IRAK-4:IRAK-1{p}:TRAF6 oligomer{ub}
TLR4:MD-2:LPS:LBP:CD14:MyD88:IRAK-4:IRAK-1{p}:TRAF6 oligomer{ub}:TAB2:TAK1_enti_e68
TLR4:MD-2:LPS:LBP:CD14:MyD88:IRAK-4:IRAK-1{p}:TRAF6 oligomer{ub}:TAB2:TAK1
TAB2:TAK1_enti_e69
TAB2:TAK1
TLR4:MD-2:LPS:LBP:CD14:MyD88:IRAK-4:IRAK-1{p}:TRAF6 oligomer{ub}:TAB2:TAK1{active}_enti_e70
TLR4:MD-2:LPS:LBP:CD14:MyD88:IRAK-4:IRAK-1{p}:TRAF6 oligomer{ub}:TAB2:TAK1{active}
IKK_enti_MO000000248
IKK
IKK{active}_enti_e71
IKK{active}
NF-KappaB:IKappaB_enti_e72
NF-KappaB:IKappaB
NF-KappaB:IKappaB{p}_enti_e73
NF-KappaB:IKappaB{p}
NF-KappaB:IKappaB{p}{ub}_enti_e74
NF-KappaB:IKappaB{p}{ub}
Proteasome degradants_enti_e75
NF-KappaB{active}_enti_e76
NF-KappaB{active}
NF-KappaB{active}_enti_e77
NF-KappaB{active}
mRNA_enti_e78
mRNA
MKK6_enti_e79
MKK6
MKK6{active}_enti_e80
MKK6{active}
JNK_enti_e81
JNK
JNK{p}_enti_e82
JNK{p}
p38{p}_enti_e83
p38{p}
p38_enti_e84
p38
AP-1_enti_e85
AP-1
AP-1{active}_enti_e86
AP-1{active}
MyD88:TRAF6:IRAK-4:IRAk-1_enti_e87
MyD88:TRAF6:IRAK-4:IRAk-1
MyD88:TRAF6:IRAK-4:IRAK-1:TLR7:ssRNA_enti_e88
MyD88:TRAF6:IRAK-4:IRAK-1:TLR7:ssRNA
IRF-7_enti_e89
IRF-7
MyD88:TRAF6{ub}:IRAK-4:IRAK-1{p}:TLR7:ssRNA:IRF-7_enti_e90
MyD88:TRAF6{ub}:IRAK-4:IRAK-1{p}:TLR7:ssRNA:IRF-7
MyD88:TRAF6{ub}:IRAK-4:IRAK-1{p}:TLR7:ssRNA:IRF-7{p}_enti_e91
MyD88:TRAF6{ub}:IRAK-4:IRAK-1{p}:TLR7:ssRNA:IRF-7{p}
IRF-7{p}_enti_e92
IRF-7{p}
MyD88:TRAF6:IRAK-4:IRAK-1{p}:TLR7:ssRNA_enti_e93
MyD88:TRAF6:IRAK-4:IRAK-1{p}:TLR7:ssRNA
MyD88:TRAF6{ub}:IRAK-4:IRAK-1{p}:TLR7:ssRNA_enti_e94
MyD88:TRAF6{ub}:IRAK-4:IRAK-1{p}:TLR7:ssRNA
IFN-alpha_enti_e95
IFN-alpha
IFN inducible genes_enti_e96
IFN inducible genes
IRF5_enti_e97
IRF5
IRF5{active}_enti_e98
IRF5{active}
IRF5{active}_enti_e99
IRF5{active}
Inflammatory cytokines_enti_e100
Inflammatory cytokines
IRF1_enti_e101
IRF1
IRF1{active}_enti_e102
IRF1{active}
IRF1{active}_enti_e103
IRF1{active}
IFN-beta_enti_e104
IFN-beta
Inos_enti_e105
Inos
IL-12p35_enti_e106
IL-12p35
Mal_enti_e107
Mal
TLR4{dimer}:MD-2:LPS:LBP:CD14:Mal_enti_e108
TLR4{dimer}:MD-2:LPS:LBP:CD14:Mal
TLR4{dimer}:MD-2:LPS:LBP:CD14_enti_e109
TLR4{dimer}:MD-2:LPS:LBP:CD14
TRIF_enti_e110
TRIF
dsRNA:TLR3:TRIF_enti_e111
dsRNA:TLR3:TRIF
TBK1:IKK-i_enti_e112
TBK1:IKK-i
dsRNA:TLR3:TRIF:TBK1:IKK-i_enti_e113
dsRNA:TLR3:TRIF:TBK1:IKK-i
dsRNA:TLR3:TRIF:TRAF6_enti_e114
dsRNA:TLR3:TRIF:TRAF6
IRF-3_enti_e115
IRF-3
IRF-3{active}_enti_e116
IRF-3{active}
IRF-3{active}_enti_e117
IRF-3{active}
dsRNA:TLR3:TRIF:TBK1{active}:IKK-i_enti_e118
dsRNA:TLR3:TRIF:TBK1{active}:IKK-i
TRAF3_enti_e119
TRAF3
NAP1_enti_e120
NAP1
RIP1_enti_e121
RIP1
dsRNA:TLR3:TRIF:RIP1_enti_e122
dsRNA:TLR3:TRIF:RIP1
TRAF6{active}_enti_e123
TRAF6{active}
TRAM_enti_e124
TRAM
TLR4{dimer}:MD-2:LPS:LBP:CD14:TRAM_enti_e125
TLR4{dimer}:MD-2:LPS:LBP:CD14:TRAM
TLR4{dimer}:MD-2:LPS:LBP:CD14:TRAM:TRIF_enti_e126
TLR4{dimer}:MD-2:LPS:LBP:CD14:TRAM:TRIF
TLR4{dimer}:MD-2:LPS:LBP:CD14:TRAM:TRIF:RIP1_enti_e127
TLR4{dimer}:MD-2:LPS:LBP:CD14:TRAM:TRIF:RIP1
TAB2:TAK1{active}_enti_e128
TAB2:TAK1{active}
Mal{p}_enti_e129
Mal{p}
TRAF1_enti_e130
TRAF1
TRIF:TRAF1_enti_e131
TRIF:TRAF1
SARM_enti_e132
SARM
dsRNA:TLR3:TRIF:SARM_enti_e133
dsRNA:TLR3:TRIF:SARM
TLR4{dimer}:MD-2:LPS:LBP:CD14:TRAM:TRIF:SARM_enti_e134
TLR4{dimer}:MD-2:LPS:LBP:CD14:TRAM:TRIF:SARM
TGF-Beta_enti_e135
TGF-Beta
MyD88{ub}_enti_e136
MyD88{ub}
ST2_enti_e137
ST2
IL-1:IL-1R_enti_e138
IL-1:IL-1R
Mal:TRAF6_enti_e139
Mal:TRAF6
Btk_enti_e140
Btk
Mal{p}_enti_e141
Mal{p}
SOCS1_enti_e142
SOCS1
Mal{p}:SOCS1_enti_e143
Mal{p}:SOCS1
Mal{p}{ub}:SOCS1_enti_e144
Mal{p}{ub}:SOCS1
Caspase-1_enti_e145
Caspase-1
PKC-delta_enti_e146
PKC-delta
Mal:PKC-delta_enti_e147
Mal:PKC-delta