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PMID: 17303405
TLR1, TLR2 and TLR6 recognize various bacterial components, including peptidoglycan and lipoproteins.</csml:comment>
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PMID: 17303405
TLR1, TLR2 and TLR6 recognize various bacterial components, including peptidoglycan and lipoproteins.
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PMID: 17303405
TLR1, TLR2 and TLR6 recognize various bacterial components, including peptidoglycan and lipoproteins.
</csml:comment>
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PMID: 17303405
TLR1, TLR2 and TLR6 recognize various bacterial components, including peptidoglycan and lipoproteins.
</csml:comment>
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PMID: 17303405
TLR1, TLR2 and TLR6 recognize various bacterial components, including peptidoglycan and lipoproteins.
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PMID: 17303405
TLR1, TLR2 and TLR6 recognize various bacterial components, including peptidoglycan and lipoproteins.
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PMID: 17303405
TLR4 and TLR5 are responsible for the recognition of bacterial lipopolysaccharide (LPS) and flagellin, respectively.
</csml:comment>
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PMID: 17303405
TLR4 and TLR5 are responsible for the recognition of bacterial lipopolysaccharide (LPS) and flagellin, respectively.
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PMID: 17303405
TLR3 detects double-stranded (ds) RNA, while TLR7 and TLR9 recognize single-stranded (ss) RNA and unmethylated DNA with CpG motifs, respectively.
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PMID: 17303405
TLR3 detects double-stranded (ds) RNA, while TLR7 and TLR9 recognize single-stranded (ss) RNA and unmethylated DNA with CpG motifs, respectively.
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PMID: 17303405
TLR3 detects double-stranded (ds) RNA, while TLR7 and TLR9 recognize single-stranded (ss) RNA and unmethylated DNA with CpG motifs, respectively
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PMID: 17303405
MDA5 recognizes polyinosinic polycytidylic acid (poly I:C) while RIG-I detects dsRNAs that have been transcribed in vitro. </csml:comment>
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PMID: 17303405
MDA5 recognizes polyinosinic polycytidylic acid (poly I:C) while RIG-I detects dsRNAs that have been transcribed in vitro.
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PMID: 17303405, 16177806, 16125763, 16127453
RIG-I and MDA5 associate with an adaptor protein, interferon-beta promoter stimulator 1 (IPS1)which contains a CARD.</csml:comment>
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PMID: 17303405, 16177806, 16125763, 16127453
RIG-I and MDA5 associate with an adaptor protein, interferon-beta promoter stimulator 1 (IPS1)which contains a CARD.</csml:comment>
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indirect</csml:comment>
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<csml:comment type="text">


PMID: 17303405
Overexpression of IPS1 induced the activation of the interferon promoters as well as NF-&#954;B.

PMID: 17303405, 16585540
FADD interacts with Caspase-8/-10 and IPS1, and a FADD-dependent pathway is responsible for the activation of NF-&#954;B downstream of IPS1.
</csml:comment>
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</csml:comment>
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<csml:comment type="text">


PMID: 17303405, 16858409
The C-terminal TRAF domain of TRAF3 associates with a TRAF binding domain found in IPS-1.</csml:comment>
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PMID: 17303405
TRAF3 recruits and activates two IKK-related kinases, TBK1 (TANK-binding kinase 1) and IKK-i (inducible I&#954;B kinase, also known as IKK epsilon).</csml:comment>
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PMID: 17303405
TRAF3 recruits and activates two IKK-related kinases, TBK1 (TANK-binding kinase 1) and IKK-i (inducible I&#954;B kinase, also known as IKK epsilon).</csml:comment>
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PMID: 17303405
TRAF3 recruits and activates two IKK-related kinases, TBK1 (TANK-binding kinase 1) and IKK-i (inducible I&#954;B kinase, also known as IKK epsilon).</csml:comment>
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PMID: 17303405
TRAF3 recruits and activates two IKK-related kinases, TBK1 (TANK-binding kinase 1) and IKK-i (inducible I&#954;B kinase, also known as IKK epsilon).</csml:comment>
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<csml:comment type="text">


PMID: 17303405, 15800576
Phosphorylation of IRF-3/-7 by these kinases induces formation of homodimers, which then translocate into the nucleus and bind to the ISREs, resulting in the expression of type I interferons and a set of interferon-inducible genes.</csml:comment>
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PMID: 17303405, 15800576
Phosphorylation of IRF-3/-7 by these kinases induces formation of homodimers, which then translocate into the nucleus and bind to the ISREs, resulting in the expression of type I interferons and a set of interferon-inducible genes.</csml:comment>
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PMID: 17303405, 15800576
Phosphorylation of IRF-3/-7 by these kinases induces formation of homodimers, which then translocate into the nucleus and bind to the ISREs, resulting in the expression of type I interferons and a set of interferon-inducible genes.</csml:comment>
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PMID: 17303405, 15800576
Phosphorylation of IRF-3/-7 by these kinases induces formation of homodimers, which then translocate into the nucleus and bind to the ISREs, resulting in the expression of type I interferons and a set of interferon-inducible genes.</csml:comment>
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PMID: 17303405, 15800576
Phosphorylation of IRF-3/-7 by these kinases induces formation of homodimers, which then translocate into the nucleus and bind to the ISREs, resulting in the expression of type I interferons and a set of interferon-inducible genes.
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PMID: 17303405, 15800576
Phosphorylation of IRF-3/-7 by these kinases induces formation of homodimers, which then translocate into the nucleus and bind to the ISREs, resulting in the expression of type I interferons and a set of interferon-inducible genes.
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PMID: 17303405, 15800576
Phosphorylation of IRF-3/-7 by these kinases induces formation of homodimers, which then translocate into the nucleus and bind to the ISREs, resulting in the expression of type I interferons and a set of interferon-inducible genes.
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PMID: 17303405, 15800576
Phosphorylation of IRF-3/-7 by these kinases induces formation of homodimers, which then translocate into the nucleus and bind to the ISREs, resulting in the expression of type I interferons and a set of interferon-inducible genes.
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PMID: 17303405, 16585540
FADD interacts with Caspase-8/-10 and IPS1, and a FADD-dependent pathway is responsible for the activation of NF-&#954;B downstream of IPS1.</csml:comment>
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PMID: 17303405, 16585540
FADD interacts with Caspase-8/-10 and IPS1, and a FADD-dependent pathway is responsible for the activation of NF-&#954;B downstream of IPS1.
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PMID: 17303405, 16585540
FADD interacts with Caspase-8/-10 and IPS1, and a FADD-dependent pathway is responsible for the activation of NF-&#954;B downstream of IPS1.
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indirect</csml:comment>
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PMID: 17303405, 16585540
FADD interacts with Caspase-8/-10 and IPS1, and a FADD-dependent pathway is responsible for the activation of NF-&#954;B downstream of IPS1.
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PMID: 17303405
Upon stimulation with poly I:C, TLR3 triggers a signaling cascade via TRIF.</csml:comment>
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PMID: 17303405
Downstream of TRIF are the signaling molecules TRAF3, TRAF6 and receptor-interacting protein-1 (RIP1).
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PMID: 17303405
Downstream of TRIF are the signaling molecules TRAF3, TRAF6 and receptor-interacting protein-1 (RIP1).
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PMID: 17303405, 16306936, 16306937
Among these, TRAF6 and RIP1 activate NF-&#954;B, whereas TRAF3 is responsible for inducing type I interferons.</csml:comment>
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PMID: 17303405, 16306936, 16306937, 15361868, 15492225, 15767370, 16612387
Upon exposure to ssRNA and CpG-DNA, MyD88 forms a complex with IL-1R-associated kinase (IRAK)-4, IRAK-1, TRAF3, TRAF6, IKK-alpha and IRF-7, and this complex is recruited to the TLR</csml:comment>
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PMID: 17303405, 16306936, 16306937, 15361868, 15492225, 15767370, 16612387
Upon exposure to ssRNA and CpG-DNA, MyD88 forms a complex with IL-1R-associated kinase (IRAK)-4, IRAK-1, TRAF3, TRAF6, IKK-alpha and IRF-7, and this complex is recruited to the TLR</csml:comment>
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PMID: 17303405
In TLR2 and TLR4 signaling, another adaptor, TIRAP (TIR domain-containing adaptor protein), is required for the recruitment of MyD88 to TLRs.</csml:comment>
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PMID: 17303405
In TLR2 and TLR4 signaling, another adaptor, TIRAP (TIR domain-containing adaptor protein), is required for the recruitment of MyD88 to TLRs.</csml:comment>
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indirect</csml:comment>
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PMID: 17303405
MyD88 triggers sequential activation of IRAK-4, IRAK-1 and TRAF6.</csml:comment>
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indirect</csml:comment>
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PMID: 17303405
MyD88 triggers sequential activation of IRAK-4, IRAK-1 and TRAF6.</csml:comment>
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indirect</csml:comment>
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PMID: 17303405
MyD88 triggers sequential activation of IRAK-4, IRAK-1 and TRAF6.
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PMID: 17303405, 16056267
Together with an ubiquitination E2 enzyme complex consisting of UBC13 and UEV1A, TRAF6 catalyzes the formation of a K63-linked polyubiquitin chain on itself and on IKK-&#947;/NF-&#954;B essential modulator (NEMO).</csml:comment>
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PMID: 17303405, 16056267
Together with an ubiquitination E2 enzyme complex consisting of UBC13 and UEV1A, TRAF6 catalyzes the formation of a K63-linked polyubiquitin chain on itself and on IKK-&#947;/NF-&#954;B essential modulator (NEMO).</csml:comment>
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PMID: 17303405, 16056267
Together with an ubiquitination E2 enzyme complex consisting of UBC13 and UEV1A, TRAF6 catalyzes the formation of a K63-linked polyubiquitin chain on itself and on IKK-&#947;/NF-&#954;B essential modulator (NEMO).
</csml:comment>
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indirect</csml:comment>
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PMID: 17303405
TRAF6 also activates TGF-&#946;-activated kinase 1 (TAK1), which phosphorylates IKK-&#946; and MAP kinase kinase 6.</csml:comment>
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PMID: 17303405
TRAF6 also activates TGF-&#946;-activated kinase 1 (TAK1), which phosphorylates IKK-&#946; and MAP kinase kinase 6.
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PMID: 17303405
TRAF6 also activates TGF-&#946;-activated kinase 1 (TAK1), which phosphorylates IKK-&#946; and MAP kinase kinase 6.</csml:comment>
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PMID: 17303405, 15665823
It was shown that IRF-5 associates with MyD88, and regulates the expression of cytokine genes, but not interferon genes, in response to stimulation with TLR ligands.</csml:comment>
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indirect</csml:comment>
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PMID: 17303405
TRAF6- and UBC13-mediated ubiquitination activates the TAK1 complex, resulting in the activation of the IKK complex and nuclear translocation of NF-&#954;B that initiates the expression of proinflammatory cytokine genes.</csml:comment>
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indirect</csml:comment>
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PMID: 17303405
TAK1 also activates MAP kinases, leading to the activation of AP-1, which is also critical for the induction of cytokine genes.</csml:comment>
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indirect</csml:comment>
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PMID: 17303405, 16688168
On the other hand, activating transcription factor 3 (ATF3) is also rapidly induced in response to LPS, and has been identified as a negative regulator of LPS-induced cytokine gene expression.</csml:comment>
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PMID: 17303405
TLR4 also recruits other TIR containing adaptors, TRAM and TRIF.</csml:comment>
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<csml:comment type="text">

PMID: 17303405
TLR4 also recruits other TIR containing adaptors, TRAM and TRIF.</csml:comment>
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Phosphorylation
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of type I interferons</csml:comment>
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genes involved in inflammatory responses.</csml:comment>
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TRAF6 also activates
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