_enti_e7
_enti_e8
_enti_e9
_enti_e1
_enti_e10
_enti_e4
_enti_e3
_enti_e2
_enti_e55
_enti_e11
_enti_e59
_enti_e53
_enti_e5
_enti_e6
_enti_e51
_enti_e52
_enti_e56
_enti_e54
_enti_e50
_enti_e58
_enti_e61
_enti_e57
_enti_e60
_enti_e62
g1_fact_g1
g1_fact_g14
g2_fact_g12
g2_fact_g13
g1_fact_g2
p1_propro_p1
PMID: 18262679,16473828
A recent study demonstrated that CD14 enhances dsRNA-mediated TLR3 activation by directly binding to poly(I:C) and mediating cellular uptake of poly(I:C)
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 18262679, 16473828
A recent study demonstrated that CD14 enhances dsRNA-mediated TLR3 activation by directly binding to poly (I: C) and mediating cellular uptake of poly (I: C)
PMID: 182626279
The internalized poly(I:C) colocalizes with CD14 and TLR3.
c4 cso30:c:InputProcess connector
c5 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 18262679,15644310
Since the extracellular domain of CD14 consists of LRRs,poly(I:C) might be transferred from CD14 to TLR3.
PMID: 182626279,11607032,16225392
TLR3 recognizes both in vitro-transcribed dsRNA and poly(I:C), suggesting that the RNA duplex and not 5′-triphosphate is critical for TLR3 activation
c6 cso30:c:InputProcess connector
c7 cso30:c:InputProcess connector
c8 cso30:c:OutputProcess connector
c9 cso30:c:OutputProcess connector
p4_propro_p4
PMID: 182626279
Once TLR3 is dimerized by internalized dsRNA, it recruits the adaptor protein TICAM-1/TRIF
c10 cso30:c:InputProcess connector
c11 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 182626279
Once TLR3 is dimerized by internalized dsRNA, it recruits the adaptor protein TICAM-1/TRIF
PMID: 18262679,12855817
TLR3 mediates signals via the adaptor protein TICAM-1/TRIF
c12 cso30:c:InputProcess connector
c17 cso30:c:InputProcess connector
c15 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 18262679
After the transient association of TLR3 with TICAM-1 through the TIR domains, TICAM-1 dissociates from TLR3 to form a speckle-like structure containing RIP1, TRAF3 and NAP1 where TICAM-1-mediated signaling is initiated.
c18 cso30:c:InputProcess connector
c16 cso30:c:OutputProcess connector
c19 cso30:c:OutputProcess connector
p7_propro_p7
PMID: 18262679,15502848
In addition, phosphorylation of two specific tyrosine residues (Tyr759 and Tyr858) in the TIR domain of TLR3 is essential for dsRNA-induced signaling
c13 cso30:c:InputProcess connector
c14 cso30:c:OutputProcess connector
p8_propro_p8
PMID:18262679
After the transient association of TLR3 with TICAM-1 through the TIR domains, TICAM-1 dissociates from TLR3 to form a speckle-like structure containing RIP1, TRAF3 and NAP1 where TICAM-1-mediated signaling is initiated.
PMID: 18262679
RIP1 associates with TICAM-1 via the PHIM domain in the C-terminal region and acts as an NF-κB activator and apoptosis mediator in TICAM-1-mediated signaling.
PMID: 18262679,15814722,15064760,14739303
Receptor-interacting protein 1 (RIP1), a kinase containing a death domain, associates with TICAM-1 via the RIP homotypic interaction motif (RHIM) domain in the C-terminal region and acts as an NF-κB inducer and apoptosis mediator in TICAM-1-mediated signaling
c20 cso30:c:InputProcess connector
c21 cso30:c:InputProcess connector
c22 cso30:c:OutputProcess connector
p9_propro_p9
PMID:18262679
After the transient association of TLR3 with TICAM-1 through the TIR domains, TICAM-1 dissociates from TLR3 to form a speckle-like structure containing RIP1, TRAF3 and NAP1 where TICAM-1-mediated signaling is initiated.
PMID: 18262679,16306937,16306936
In addition, TRAF3 is involved in the TLR3-TICAM-1-mediated IRF-3 activation
PMID: 18262679,15611223
It is reported that NF-κB activating kinase (NAK)-associated protein 1 (NAP1) participates in the recruitment of IRF-3 kinases to the N-terminal region of TICAM-1
PMID: 18262679
TRAF3 and NAP1 participate in the recruitment and activation of the IRF-3 kinases TBK1 and IKKvar epsilon.
c23 cso30:c:InputProcess connector
c24 cso30:c:InputProcess connector
c25 cso30:c:InputProcess connector
c26 cso30:c:OutputProcess connector
p10_propro_p10
PMID: 18262679
TRAF6 directly binds to the N-terminal region of TICAM-1 through the TRAF domain
PMID: 18262679,14982987
Although TRAF6 is required for NF-κB activation in MEFs,poly(I:C)-induced NF-κB activation is not impaired in TRAF6-deficient macrophages
c27 cso30:c:InputProcess connector
c28 cso30:c:InputProcess connector
c29 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 18262679,14982987
Although TRAF6 is required for NF-κB activation in MEFs,poly(I:C)-induced NF-κB activation is not impaired in TRAF6-deficient macrophages
c30 cso30:c:InputAssociation connector
c31 cso30:c:InputProcess connector
c32 cso30:c:OutputProcess connector
p12_propro_p12
PMID: 18262679
RIP1 associates with TICAM-1 via the PHIM domain in the C-terminal region and acts as an NF-κB activator and apoptosis mediator in TICAM-1-mediated signaling.
PMID: 18262679,15814722,15064760,14739303
Receptor-interacting protein 1 (RIP1), a kinase containing a death domain, associates with TICAM-1 via the RIP homotypic interaction motif (RHIM) domain in the C-terminal region and acts as an NF-κB inducer and apoptosis mediator in TICAM-1-mediated signaling
PMID: 18262679
SARM and TICAM-1 have been shown to interact and SARM strongly suppresses NF-κB activation as well as IRF-3 activation by TICAM-1.
c33 cso30:c:InputAssociation connector
c34 cso30:c:InputProcess connector
c49 cso30:c:InputInhibitor connector
c35 cso30:c:OutputProcess connector
p13_propro_p13
PMID: 18262679
RIP1 associates with TICAM-1 via the PHIM domain in the C-terminal region and acts as an NF-κB activator and apoptosis mediator in TICAM-1-mediated signaling.
PMID: 18262679,15814722,15064760,14739303
Receptor-interacting protein 1 (RIP1), a kinase containing a death domain, associates with TICAM-1 via the RIP homotypic interaction motif (RHIM) domain in the C-terminal region and acts as an NF-κB inducer and apoptosis mediator in TICAM-1-mediated signaling
c36 cso30:c:InputAssociation connector
p14_propro_p14
PMID: 18262679
TRAF3 and NAP1 participate in the recruitment and activation of the IRF-3 kinases TBK1 and IKKvar epsilon.
PMID: 18262679,12702806,12692549
Once TICAM-1 is oligomerized, the serine-threonine kinases, TANK-binding kinase 1 (TBK-1; also called NAK or T2K) and IκB kinase-related kinase var epsilon (IKK-var epsilon; also called IKK-i), are activated and phosphorylate IRF-3
c37 cso30:c:InputProcess connector
c38 cso30:c:InputProcess connector
c39 cso30:c:InputProcess connector
c40 cso30:c:OutputProcess connector
p15_propro_p15
PMID: 18262679, 12702806, 12692549
Once TICAM-1 is oligomerized, the serine-threonine kinases, TANK-binding kinase 1 (TBK-1; also called NAK or T2K) and IκB kinase-related kinase var epsilon (IKK-var epsilon; also called IKK-i), are activated and phosphorylate IRF-3
PMID: 18262679
SARM and TICAM-1 have been shown to interact and SARM strongly suppresses NF-κB activation as well as IRF-3 activation by TICAM-1.
c41 cso30:c:InputAssociation connector
c42 cso30:c:InputProcess connector
c50 cso30:c:InputInhibitor connector
c43 cso30:c:OutputProcess connector
p16_propro_p16
PMID: 18262679,11070172
Phosphoprylated IRF-3 translocates into the nucleus and induces IFN-beta gene transcription
PMID: 18262679
Phosphorylated IRF-3 translocates into the nucleus and together with NF-KappaB and AP-1 induces IFN-beta gene transcription.
c44 cso30:c:InputProcess connector
c45 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 18262679
SARM and TICAM-1 have been shown to interact and SARM strongly suppresses NF-κB activation as well as IRF-3 activation by TICAM-1.
c46 cso30:c:InputProcess connector
c47 cso30:c:InputProcess connector
c48 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 18262679
Phosphorylated IRF-3 translocates into the nucleus and together with NF-κB and AP-1 induces IFN-beta gene transcription
c51 cso30:c:InputProcess connector
c52 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 18262679
Phosphorylated IRF-3 translocates into the nucleus and together with NF-kappaB and AP-1 induces IFN-beta gene transcription
c53 cso30:c:InputAssociation connector
c54 cso30:c:InputAssociation connector
c55 cso30:c:InputAssociation connector
c92 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 18262679
Phosphatidylinositol 3-kinase (PI3-K) is recruited to these residues, and is required for full phosphorylation and activation of IRF-3.
c56 cso30:c:InputProcess connector
c57 cso30:c:InputProcess connector
c58 cso30:c:OutputProcess connector
p21_propro_p21
PMID: 18262679,16858407
TLR3 also associates with c-Src tyrosine kinase on the endosome in response to dsRNA
c59 cso30:c:InputProcess connector
c60 cso30:c:InputProcess connector
c61 cso30:c:OutputProcess connector
p22_propro_p22
Phosphatidylinositol 3-kinase (PI3-K) is recruited to these residues, and is required for full phosphorylation and activation of IRF-3.
c62 cso30:c:InputAssociation connector
c63 cso30:c:InputProcess connector
c64 cso30:c:OutputProcess connector
p23_propro_p23
PMID: 18262679
The Src kinase inhibitor markedly inhibits dsRNA-elicited phosphorylation of Akt, a downstream target of PI3-K.
c66 cso30:c:InputProcess connector
c65 cso30:c:InputAssociation connector
c68 cso30:c:InputInhibitor connector
c67 cso30:c:OutputProcess connector
p24_propro_p24
PMID: 18262679,12855817
This activates the transcription factors interferon regulatory factor 3 (IRF-3), NF-KappaB, and AP-1 (a complex of activating transcription factor 2 (ATF2) and JUN), leading to the induction of type I IFN (especially IFN-beta), cytokine/chemokine production and dendritic cell (DC) maturation
c69 cso30:c:InputAssociation connector
c70 cso30:c:InputProcess connector
c71 cso30:c:OutputProcess connector
p25_propro_p25
PMID: 18262679
Phosphorylated IRF-3 translocates into the nucleus and together with NF-kappaB and AP-1 induces IFN-beta gene transcription
c72 cso30:c:InputProcess connector
c73 cso30:c:OutputProcess connector
p26_propro_p26
PMID: 18262679, 12855817
This activates the transcription factors interferon regulatory factor 3 (IRF-3), NF-KappaB, and AP-1 (a complex of activating transcription factor 2 (ATF2) and JUN), leading to the induction of type I IFN (especially IFN-beta), cytokine/chemokine production and dendritic cell (DC) maturation
c75 cso30:c:InputAssociation connector
c76 cso30:c:OutputProcess connector
p26_propro_p27
PMID: 18262679, 12855817
This activates the transcription factors interferon regulatory factor 3 (IRF-3), NF-KappaB, and AP-1 (a complex of activating transcription factor 2 (ATF2) and JUN), leading to the induction of type I IFN (especially IFN-beta), cytokine/chemokine production and dendritic cell (DC) maturation
c78 cso30:c:InputAssociation connector
c79 cso30:c:OutputProcess connector
p26_propro_p28
PMID: 18262679, 12855817
This activates the transcription factors interferon regulatory factor 3 (IRF-3), NF-KappaB, and AP-1 (a complex of activating transcription factor 2 (ATF2) and JUN), leading to the induction of type I IFN (especially IFN-beta), cytokine/chemokine production and dendritic cell (DC) maturation
c81 cso30:c:InputAssociation connector
c82 cso30:c:OutputProcess connector
p29_propro_p29
PMID: 18262679,17038590,17038589
RIG-I and MDA5 recognize 5′-triphosphate-containing ssRNA/dsRNA and poly(I:C), respectively and induce IFN-alpha/beta production
c83 cso30:c:InputProcess connector
c84 cso30:c:InputProcess connector
c85 cso30:c:OutputProcess connector
p29_propro_p30
PMID: 18262679,17038590,17038589
RIG-I and MDA5 recognize 5′-triphosphate-containing ssRNA/dsRNA and poly(I:C), respectively and induce IFN-alpha/beta production
c86 cso30:c:InputProcess connector
c87 cso30:c:InputProcess connector
c88 cso30:c:OutputProcess connector
p29_propro_p31
PMID: 18262679,17038590,17038589
RIG-I and MDA5 recognize 5′-triphosphate-containing ssRNA/dsRNA and poly(I:C), respectively and induce IFN-alpha/beta production
c89 cso30:c:InputProcess connector
c90 cso30:c:InputProcess connector
c91 cso30:c:OutputProcess connector
p32_propro_p32
PMID: 18262679, 17038590, 17038589
RIG-I and MDA5 recognize 5′-triphosphate-containing ssRNA/dsRNA and poly(I:C), respectively and induce IFN-alpha/beta production
c93 cso30:c:InputAssociation connector
c94 cso30:c:InputAssociation connector
c95 cso30:c:OutputProcess connector
p32_propro_p33
PMID: 18262679, 17038590, 17038589
RIG-I and MDA5 recognize 5′-triphosphate-containing ssRNA/dsRNA and poly(I:C), respectively and induce IFN-alpha/beta production
c96 cso30:c:InputAssociation connector
c97 cso30:c:InputAssociation connector
c98 cso30:c:OutputProcess connector
p32_propro_p34
PMID: 18262679, 17038590, 17038589
RIG-I and MDA5 recognize 5′-triphosphate-containing ssRNA/dsRNA and poly(I:C), respectively and induce IFN-alpha/beta production
c99 cso30:c:InputAssociation connector
c100 cso30:c:InputAssociation connector
c101 cso30:c:OutputProcess connector
p32_propro_p35
PMID: 18262679, 17038590, 17038589
RIG-I and MDA5 recognize 5′-triphosphate-containing ssRNA/dsRNA and poly(I:C), respectively and induce IFN-alpha/beta production
c102 cso30:c:InputAssociation connector
c103 cso30:c:InputAssociation connector
c104 cso30:c:OutputProcess connector
p32_propro_p36
PMID: 18262679, 17038590, 17038589
RIG-I and MDA5 recognize 5′-triphosphate-containing ssRNA/dsRNA and poly(I:C), respectively and induce IFN-alpha/beta production
c105 cso30:c:InputAssociation connector
c106 cso30:c:InputAssociation connector
c107 cso30:c:OutputProcess connector
p32_propro_p37
PMID: 18262679, 17038590, 17038589
RIG-I and MDA5 recognize 5′-triphosphate-containing ssRNA/dsRNA and poly(I:C), respectively and induce IFN-alpha/beta production
c108 cso30:c:InputAssociation connector
c110 cso30:c:InputAssociation connector
c109 cso30:c:OutputProcess connector
p38_propro_p38
PMID: 18262679, 12855817
This activates the transcription factors interferon regulatory factor 3 (IRF-3), NF-KappaB, and AP-1 (a complex of activating transcription factor 2 (ATF2) and JUN), leading to the induction of type I IFN (especially IFN-beta), cytokine/chemokine production and dendritic cell (DC) maturation
c112 cso30:c:InputAssociation connector
c111 cso30:c:OutputProcess connector
p38_propro_p39
PMID: 18262679, 12855817
This activates the transcription factors interferon regulatory factor 3 (IRF-3), NF-KappaB, and AP-1 (a complex of activating transcription factor 2 (ATF2) and JUN), leading to the induction of type I IFN (especially IFN-beta), cytokine/chemokine production and dendritic cell (DC) maturation
c74 cso30:c:InputAssociation connector
c113 cso30:c:OutputProcess connector
p38_propro_p40
PMID: 18262679, 12855817
This activates the transcription factors interferon regulatory factor 3 (IRF-3), NF-KappaB, and AP-1 (a complex of activating transcription factor 2 (ATF2) and JUN), leading to the induction of type I IFN (especially IFN-beta), cytokine/chemokine production and dendritic cell (DC) maturation
c115 cso30:c:InputAssociation connector
c114 cso30:c:OutputProcess connector
TLR3_enti_MO000019398
TLR3
dsRNA,Poly (I:C)_enti_MO000022224
dsRNA,Poly (I:C)
CD14_enti_MO000018132
CD14
dsRNA:CD14_enti_e12
dsRNA:CD14
dsRNA:CD14_enti_e13
dsRNA:CD14
DDX58_enti_MO000066987
DDX58
IFIH1_enti_MO000103999
IFIH1
dsRNA_enti_e15
dsRNA
dsRNA:TLR3_enti_MO000041446
dsRNA:TLR3
dsRNA:TLR3(2)_enti_e14
dsRNA:TLR3(2)
TRIF_enti_MO000041125
TRIF
dsRNA:TLR3(2):TRIF_enti_MO000041437
dsRNA:TLR3(2):TRIF
dsRNA:TLR3(2){p}_enti_e16
dsRNA:TLR3(2){p}
RIP1_enti_MO000000065
RIP1
TRIF:RIP1_enti_e17
TRIF:RIP1
TRAF3_enti_MO000016963
TRAF3
Nap1_enti_e18
Nap1
TRIF:TRAF3:Nap1_enti_e19
TRIF:TRAF3:Nap1
TRAF6_enti_MO000000212
TRAF6
TRIF:TRAF6_enti_e20
TRIF:TRAF6
NF-kappaB_enti_MO000000058
NF-kappaB
NF-kappaB{active}_enti_e21
NF-kappaB{active}
TBK1_enti_MO000019331
TBK1
IKK-i_enti_MO000016608
IKK-i
TRIF:TRAF3:Nap1:TBK1:IKK-i_enti_e22
TRIF:TRAF3:Nap1:TBK1:IKK-i
IRF-3_enti_MO000007694
IRF-3
IRF-3{p}_enti_MO000041456
IRF-3{p}
IRF-3{p}_enti_e23
IRF-3{p}
SARM_enti_e24
SARM
TRIF:SARM_enti_e25
TRIF:SARM
NF-kappaB{active}_enti_e26
NF-kappaB{active}
AP-1{active}_enti_MO000000276
AP-1{active}
PI3K_enti_MO000000030
PI3K
dsRNA:TLR3(2){p}:PI3K_enti_e27
dsRNA:TLR3(2){p}:PI3K
Src_enti_MO000000085
Src
dsRNA:TLR3(2){p}:PI3K:Src_enti_e28
dsRNA:TLR3(2){p}:PI3K:Src
AKT_enti_MO000000048
AKT
AKT{p}_enti_e29
AKT{p}
Src kinase inhibitor_enti_e30
Src kinase inhibitor
AP-1_enti_e31
AP-1
AP-1{active}_enti_e32
AP-1{active}
Cytokine/Chemokine_enti_e33
Cytokine/Chemokine
Cytokine/Chemokine_enti_e34
Cytokine/Chemokine
ssRNA_enti_e35
ssRNA
Poly(I:C)_enti_e36
Poly(I:C)
DDX58:dsRNA_enti_e37
DDX58:dsRNA
DDX58:ssRNA_enti_e38
DDX58:ssRNA
IFIH1:Poly(I:C)_enti_e39
IFIH1:Poly(I:C)
IFN-beta_enti_G010228
IFN-beta
IFN-alpha_enti_e40
IFN-alpha
IFNbeta_enti_MO000016660
IFNbeta
IFNalpha_enti_e41
IFNalpha