_enti_e7
_enti_e8
_enti_e1
_enti_e9
_enti_e10
_enti_e3
_enti_e2
_enti_e4
_enti_e55
_enti_e59
_enti_e53
_enti_e54
_enti_e52
_enti_e51
_enti_e50
_enti_e56
_enti_e61
_enti_e57
_enti_e58
_enti_e62
_enti_e60
g2_fact_g2
g1_fact_g1
g1_fact_g14
g2_fact_g12
g2_fact_g13
p1_propro_p1
PMID: 12213596
Once produced, these secreted proteins act in a paracrine fashion to induce gene expression in target cells in the adjacent microenvironment, through engagement of cell surface IFN receptors and the JAK-STAT signaling pathway.
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 12213596, 11585785, 11544356
STAT1/2 heterodimers, in conjunction with interferon-stimulated gene factor 3gamma (ISGF3gamma/IRF-9) bind to ISRE found in numerous IFN-induced genes, such as 2′5′ oligoadenylate synthase and the dsRNA activated kinase (PKR), resulting in the induction of proteins which impair viral gene expression and replication [2 and 3].
c4 cso30:c:InputProcess connector
c5 cso30:c:InputProcess connector
c6 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 12213596, 11585785, 11544356
STAT1/2 heterodimers, in conjunction with interferon-stimulated gene factor 3gamma (ISGF3gamma/IRF-9) bind to ISRE found in numerous IFN-induced genes, such as 2′5′ oligoadenylate synthase and the dsRNA activated kinase (PKR), resulting in the induction of proteins which impair viral gene expression and replication [2 and 3].
c7 cso30:c:InputProcess connector
c8 cso30:c:OutputProcess connector
p4_propro_p4
PMID: 12213596, 11585785, 11544356
STAT1/2 heterodimers, in conjunction with interferon-stimulated gene factor 3gamma (ISGF3gamma/IRF-9) bind to ISRE found in numerous IFN-induced genes, such as 2′5′ oligoadenylate synthase and the dsRNA activated kinase (PKR), resulting in the induction of proteins which impair viral gene expression and replication [2 and 3].
c11 cso30:c:InputProcess connector
c12 cso30:c:InputProcess connector
c13 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 12213596, 11585785, 11544356
STAT1/2 heterodimers, in conjunction with interferon-stimulated gene factor 3gamma (ISGF3gamma/IRF-9) bind to ISRE found in numerous IFN-induced genes, such as 2′5′ oligoadenylate synthase and the dsRNA activated kinase (PKR), resulting in the induction of proteins which impair viral gene expression and replication [2 and 3].
c9 cso30:c:InputProcess connector
c10 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 12213596, 11585785, 11544356
STAT1/2 heterodimers, in conjunction with interferon-stimulated gene factor 3gamma (ISGF3gamma/IRF-9) bind to ISRE found in numerous IFN-induced genes, such as 2′5′ oligoadenylate synthase and the dsRNA activated kinase (PKR), resulting in the induction of proteins which impair viral gene expression and replication [2 and 3].
PMID: 12213596, 11585785
The intracellular target of dsRNA is PKR, a Ser/Thr kinase that is induced by IFNs and activated catalytically through the binding of dsRNA.
c14 cso30:c:InputAssociation connector
c16 cso30:c:OutputProcess connector
p7_propro_p7
PMID: 12213596, 11585785, 11544356
STAT1/2 heterodimers, in conjunction with interferon-stimulated gene factor 3gamma (ISGF3gamma/IRF-9) bind to ISRE found in numerous IFN-induced genes, such as 2′5′ oligoadenylate synthase and the dsRNA activated kinase (PKR), resulting in the induction of proteins which impair viral gene expression and replication [2 and 3].
c15 cso30:c:InputAssociation connector
c17 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 12213596, 11191641
TLR4 is essential for the recognition of LPS, the major component of the outer membrane of Gram-negative bacteria.
c18 cso30:c:InputProcess connector
c19 cso30:c:InputProcess connector
c20 cso30:c:OutputProcess connector
p9_propro_p9
PMID: 12213596, 11062499
The innate immune response to RSV is mediated by the interaction of fusion protein of RSV with TLR4 and CD-14.
c21 cso30:c:InputProcess connector
c22 cso30:c:InputProcess connector
c23 cso30:c:InputProcess connector
c25 cso30:c:OutputProcess connector
p10_propro_p10
PMID: 12213596, 11554921
TLR2 in conjunction with TLR6, and possibly other TLRs, is essential for the recognition of lipoproteins and peptidoglycan molecules found on pathogens such as Gram-negative bacteria, Gram-positive bacteria, mycobacteria, spirochetes, and zymozan from fungi.
c24 cso30:c:InputProcess connector
c46 cso30:c:InputProcess connector
c26 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 12213596, 11554921
TLR2 in conjunction with TLR6, and possibly other TLRs, is essential for the recognition of lipoproteins and peptidoglycan molecules found on pathogens such as Gram-negative bacteria, Gram-positive bacteria, mycobacteria, spirochetes, and zymozan from fungi.
c27 cso30:c:InputProcess connector
c47 cso30:c:InputProcess connector
c28 cso30:c:OutputProcess connector
p12_propro_p12
PMID: 12213596, 11554921
TLR2 in conjunction with TLR6, and possibly other TLRs, is essential for the recognition of lipoproteins and peptidoglycan molecules found on pathogens such as Gram-negative bacteria, Gram-positive bacteria, mycobacteria, spirochetes, and zymozan from fungi.
c29 cso30:c:InputProcess connector
c48 cso30:c:InputProcess connector
c30 cso30:c:OutputProcess connector
p13_propro_p13
PMID: 12213596, 11607032
TLR3 is associated with the binding and activation of dsRNA signaling.
c31 cso30:c:InputProcess connector
c33 cso30:c:InputProcess connector
c32 cso30:c:OutputProcess connector
p14_propro_p14
PMID: 12213596, 11554921
TLR5 is responsible for the recognition of flagellin, a monomeric constituent of bacterial flagella.
c34 cso30:c:InputProcess connector
c35 cso30:c:InputProcess connector
c36 cso30:c:OutputProcess connector
p15_propro_p15
PMID: 12213596, 11554921, 11470918
TLR9 is essential for the recognition of bacterial CpG DNA, a motif found in non-methylated bacterial DNA.
c37 cso30:c:InputProcess connector
c38 cso30:c:InputProcess connector
c39 cso30:c:OutputProcess connector
p16_propro_p16
PMID: 12213596
Activated TLRs associate with a cytoplasmic adapter molecule, MyD88, through the homophilic interaction between their TIR domains.
c40 cso30:c:InputProcess connector
c41 cso30:c:InputProcess connector
c42 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 12213596
Activated TLRs associate with a cytoplasmic adapter molecule, MyD88, through the homophilic interaction between their TIR domains.
c43 cso30:c:InputProcess connector
c44 cso30:c:InputProcess connector
c45 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 12213596
MyD88 interacts with the Ser/Thr kinase IRAK which subsequently activates the TRAF6 adapter.
c49 cso30:c:InputProcess connector
c50 cso30:c:InputProcess connector
c51 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 12213596
MyD88 interacts with the Ser/Thr kinase IRAK which subsequently activates the TRAF6 adapter.
c52 cso30:c:InputProcess connector
c54 cso30:c:InputProcess connector
c53 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 12213596
MyD88 interacts with the Ser/Thr kinase IRAK which subsequently activates the TRAF6 adapter.
c55 cso30:c:InputProcess connector
c56 cso30:c:OutputProcess connector
p21_propro_p21
PMID: 12213596
TRAF6 in turn activates the stress-related MAPK pathways JNK and p38, as well as the IKK complex leading to AP-1 and NF-kappaB activation respectively, and the induction of cytokines such as TNF-alpha and IL-6.
PMID: 11213596
The rate limiting step in this process is the activation of the IKK complex, which is composed of two catalytic subunitsIKKalpha and IKKbeta and one regulatory subunit IKKgamma.
c63 cso30:c:InputProcess connector
c65 cso30:c:InputAssociation connector
c64 cso30:c:OutputProcess connector
p24_propro_p24
PMID: 12213596
Virus infection results in the activation of multiple signaling cascades resulting in the phosphorylation of ATF-2, C-Jun, IRF-3, and NF-kapppaB.
PMID: 12213596
Following virus replication, the generation of dsRNA activates the stress-induced MAPK pathway p38/JNK resulting in the AP-1 activation.
PMID: 12213596
The heterodimers ATF-2/c-Jun are expressed as nuclear proteins that are activated by phosphorylation of their activation domains by p38/JNK.
c235 cso30:c:InputAssociation connector
c275 cso30:c:InputProcess connector
c273 cso30:c:OutputProcess connector
p26_propro_p26
PMID: 1213596
The NF-kappaB factors are retained in the cytoplasm of non-stimulated cells in association with inhibitory subunitsinhibitors kappa B (IκBs); dsRNA- and virus-induced phosphorylation at conserved N-terminal residues (Ser 32 and 36) of IkappaB-alpha is accomplished by the IκB kinase (IKK) complex.
PMID: 12213596, 10837071
Phosphorylation triggers a signal that induces ubiquitin-dependent, proteasome-mediated degradation of IkappaB-alpha, and subsequent nuclear translocation of the NF-kappaB dimers.
PMID: 12213596, 10626894, 10848580
Another putative target of PKR is the IKKbeta subunit of the IKK complex that physically associates with PKR [20] and is believed to mediate the NF-kappaB activation in a manner that is independent of PKR kinase activity.
PMID: 12213596, 11607032
Activation of TLR-3 induces the activation of both MAPK and NF-kappaB pathways, independently of the adapter protein MyD88.
PMID: 12213596
These experiments imply that MEKK1 can induce IRF-3 and ATF2/c-Jun through the JNK pathway and NF-kappaB through the IKK pathway, resulting in the integration of multiple signal transduction pathways leading to the proper assembly of the IFN-beta enhanceosome.
c72 cso30:c:InputAssociation connector
c73 cso30:c:InputProcess connector
c74 cso30:c:OutputProcess connector
p27_propro_p27
PMID: 12213596, 10837071
Phosphorylation triggers a signal that induces ubiquitin-dependent, proteasome-mediated degradation of IkappaB-alpha, and subsequent nuclear translocation of the NF-kappaB dimers.
PMID: 12213596, 10626894, 10848580
Another putative target of PKR is the IKKbeta subunit of the IKK complex that physically associates with PKR [20] and is believed to mediate the NF-kappaB activation in a manner that is independent of PKR kinase activity.
PMID: 12213596, 11607032
Activation of TLR-3 induces the activation of both MAPK and NF-kappaB pathways, independently of the adapter protein MyD88.
PMID: 12213596
These experiments imply that MEKK1 can induce IRF-3 and ATF2/c-Jun through the JNK pathway and NF-kappaB through the IKK pathway, resulting in the integration of multiple signal transduction pathways leading to the proper assembly of the IFN-beta enhanceosome.
c85 cso30:c:InputProcess connector
c76 cso30:c:OutputProcess connector
c83 cso30:c:OutputProcess connector
p28_propro_p28
PMID: 12213596, 10837071
Phosphorylation triggers a signal that induces ubiquitin-dependent, proteasome-mediated degradation of IkappaB-alpha, and subsequent nuclear translocation of the NF-kappaB dimers.
c78 cso30:c:InputProcess connector
c79 cso30:c:OutputProcess connector
p29_propro_p29
PMID: 12213596
TRAF6 in turn activates the stress-related MAPK pathways JNK and p38, as well as the IKK complex leading to AP-1 and NF-kappaB activation respectively, and the induction of cytokines such as TNF-alpha and IL-6.
c80 cso30:c:InputAssociation connector
c77 cso30:c:OutputProcess connector
p30_propro_p30
PMID: 12213596
TRAF6 in turn activates the stress-related MAPK pathways JNK and p38, as well as the IKK complex leading to AP-1 and NF-kappaB activation respectively, and the induction of cytokines such as TNF-alpha and IL-6.
c81 cso30:c:InputAssociation connector
c82 cso30:c:OutputProcess connector
p31_propro_p31
PMID: 12213596, 10837071
Phosphorylation triggers a signal that induces ubiquitin-dependent, proteasome-mediated degradation of IkappaB-alpha, and subsequent nuclear translocation of the NF-kappaB dimers.
PMID: 12213596, 10626894, 10848580
Another putative target of PKR is the IKKbeta subunit of the IKK complex that physically associates with PKR [20] and is believed to mediate the NF-kappaB activation in a manner that is independent of PKR kinase activity.
PMID: 12213596, 11607032
Activation of TLR-3 induces the activation of both MAPK and NF-kappaB pathways, independently of the adapter protein MyD88.
PMID: 12213596
These experiments imply that MEKK1 can induce IRF-3 and ATF2/c-Jun through the JNK pathway and NF-kappaB through the IKK pathway, resulting in the integration of multiple signal transduction pathways leading to the proper assembly of the IFN-beta enhanceosome.
c75 cso30:c:InputProcess connector
c84 cso30:c:OutputProcess connector
p32_propro_p32
PMID: 12213596
Following virus replication, the generation of dsRNA activates the stress-induced MAPK pathway p38/JNK resulting in the AP-1 activation.
PMID: 12213596
The heterodimers ATF-2/c-Jun are expressed as nuclear proteins that are activated by phosphorylation of their activation domains by p38/JNK.
c86 cso30:c:InputProcess connector
c89 cso30:c:InputAssociation connector
c88 cso30:c:InputAssociation connector
c87 cso30:c:OutputProcess connector
p33_propro_p33
PMID: 12213596
TRAF6 in turn activates the stress-related MAPK pathways JNK and p38, as well as the IKK complex leading to AP-1 and NF-kappaB activation respectively, and the induction of cytokines such as TNF-alpha and IL-6.
c90 cso30:c:InputAssociation connector
c92 cso30:c:OutputProcess connector
p34_propro_p34
PMID: 12213596
TRAF6 in turn activates the stress-related MAPK pathways JNK and p38, as well as the IKK complex leading to AP-1 and NF-kappaB activation respectively, and the induction of cytokines such as TNF-alpha and IL-6.
c91 cso30:c:InputAssociation connector
c93 cso30:c:OutputProcess connector
p35_propro_p35
PMID: 12213596
The dsRNA mimetic poly(I:C) has the capacity to induce a subset of ISGs and cytokines that function to impede viral replication.
c94 cso30:c:InputProcess connector
c95 cso30:c:InputProcess connector
c96 cso30:c:OutputProcess connector
p36_propro_p36
PMID: 12213596
The dsRNA mimetic poly(I:C) has the capacity to induce a subset of ISGs and cytokines that function to impede viral replication.
c98 cso30:c:InputAssociation connector
c245 cso30:c:OutputProcess connector
p37_propro_p37
PMID: 12213596
The dsRNA mimetic poly(I:C) has the capacity to induce a subset of ISGs and cytokines that function to impede viral replication.
c100 cso30:c:InputAssociation connector
c99 cso30:c:OutputProcess connector
p38_propro_p38
PMID: 12213596, 11401490
Indeed, PACT, a dsRNA-binding protein originally identified as an activator of PKR, was shown to enhance IRF-3 activation.
c101 cso30:c:InputProcess connector
c160 cso30:c:InputAssociation connector
c102 cso30:c:OutputProcess connector
p39_propro_p39
PMID: 12213596
Viral nucleocapsid (N) and dsRNA activate VAK, a virus activated kinase, leading to C-terminal phosphorylation of IRF-3.
PMID: 12213596
Virus-mediated activation of IRF-3 through VAK is dependent on viral entry and transcription, since replication deficient virus failed to induce IRF-3 activity.
PMID: 12213596, 11907205
Indeed, a recent study has shown that the N nucleocapsid (N) protein of MeV induced IRF-3 activation via the induction of VAK.
c104 cso30:c:InputProcess connector
c103 cso30:c:InputAssociation connector
c105 cso30:c:OutputProcess connector
p40_propro_p40
PMID: 12213596
IRF-3 C-terminal phosphorylation results in homodimerization, accumulation in the nucleus through CBP association, activation of genes through DNA binding and degradation by the proteasome pathway.
c106 cso30:c:InputProcess connector
c107 cso30:c:OutputProcess connector
p41_propro_p41
PMID: 12213596, 9566918, 9463386, 10082512
In addition, IRF-3 C-terminal phosphorylation is required for association with the histone acetyltransferase nuclear proteins CBP and p300 [10, 13 and 23] causing IRF-3, which normally shuttles into and out of the nucleus, to become predominantly nuclear.
PMID: 12213596, 11035028
Indeed, as opposed to the observation made by Kim’s group, stress-inducers and DNA damaging agents failed to induce nuclear accumulation through CBP association or transcriptional activation of RANTES promoter.
c108 cso30:c:InputProcess connector
c110 cso30:c:InputProcess connector
c109 cso30:c:OutputProcess connector
p42_propro_p42
PMID: 12213596, 9566918, 9463386, 10082512
In addition, IRF-3 C-terminal phosphorylation is required for association with the histone acetyltransferase nuclear proteins CBP and p300 [10, 13 and 23] causing IRF-3, which normally shuttles into and out of the nucleus, to become predominantly nuclear.
PMID: 12213596, 11035028
Indeed, as opposed to the observation made by Kim’s group, stress-inducers and DNA damaging agents failed to induce nuclear accumulation through CBP association or transcriptional activation of RANTES promoter.
c111 cso30:c:InputProcess connector
c112 cso30:c:OutputProcess connector
p44_propro_p44
PMID: 12213596, 9566918, 9660935, 9463386
The activated form of IRF-3, bound to CBP, induces transcription through distinct positive regulatory domains in the type 1 IFN promoters, and through select ISRE sites.
c113 cso30:c:InputProcess connector
c114 cso30:c:InputProcess connector
c115 cso30:c:OutputProcess connector
p43_propro_p43
PMID: 12213596
Genes targeted by IRF-3 include not only the classical IRF-responsive genes IFNalpha1 and beta but also new candidates such as genes encoding for the chemokine RANTES and the cytokine IL-15.
c119 cso30:c:InputAssociation connector
c116 cso30:c:OutputProcess connector
p45_propro_p45
PMID: 12213596
Genes targeted by IRF-3 include not only the classical IRF-responsive genes IFNalpha1 and beta but also new candidates such as genes encoding for the chemokine RANTES and the cytokine IL-15.
PMID: 12213596, 10678979, 11896392
Treatment of murine macrophages with LPS also induces the production of IFNbeta, suggesting the activation of some IRF members by LPS [4 and 5] and also implying a role for ISGs in response to bacterial infection.
c120 cso30:c:InputAssociation connector
c117 cso30:c:OutputProcess connector
p46_propro_p46
PMID: 12213596
Genes targeted by IRF-3 include not only the classical IRF-responsive genes IFNalpha1 and beta but also new candidates such as genes encoding for the chemokine RANTES and the cytokine IL-15.
PMID: 12213596, 11035028
Indeed, as opposed to the observation made by Kim’s group, stress-inducers and DNA damaging agents failed to induce nuclear accumulation through CBP association or transcriptional activation of RANTES promoter.
c121 cso30:c:InputAssociation connector
c118 cso30:c:OutputProcess connector
p47_propro_p47
PMID: 12213596
Genes targeted by IRF-3 include not only the classical IRF-responsive genes IFNalpha1 and beta but also new candidates such as genes encoding for the chemokine RANTES and the cytokine IL-15.
c123 cso30:c:InputAssociation connector
c122 cso30:c:OutputProcess connector
p48_propro_p48
PMID: 12213596
Recently, the IFN-stimulated gene ISG56 was shown to be a direct target of IRF-3.
c125 cso30:c:InputAssociation connector
c124 cso30:c:OutputProcess connector
p49_propro_p49
PMID: 12213596, 11118224
Interestingly, ISG56 acts as an inhibitor of cell proliferation by downregulating protein synthesis through interaction with the p48 subunit of eIF-3.
c126 cso30:c:InputProcess connector
c127 cso30:c:InputProcess connector
c128 cso30:c:OutputProcess connector
p50_propro_p50
PMID: 12213596, 11118224
Interestingly, ISG56 acts as an inhibitor of cell proliferation by downregulating protein synthesis through interaction with the p48 subunit of eIF-3.
c129 cso30:c:InputInhibitor connector
p51_propro_p51
PMID: 12213596, 11118224
Thus, the translation inhibitory function of ISG56 may provide, at least in part, a mechanistic explanation for the ability of IRF-3 5D to mediate apoptosis.
c130 cso30:c:InputAssociation connector
p52_propro_p52
PMID: 12213596, 11118224
Thus, the translation inhibitory function of ISG56 may provide, at least in part, a mechanistic explanation for the ability of IRF-3 5D to mediate apoptosis.
c132 cso30:c:InputAssociation connector
c131 cso30:c:OutputProcess connector
p53_propro_p53
PMID: 12213596
Virus-mediated activation of IRF-3 through VAK is dependent on viral entry and transcription, since replication deficient virus failed to induce IRF-3 activity.
c133 cso30:c:InputProcess connector
c135 cso30:c:InputAssociation connector
c134 cso30:c:OutputProcess connector
p54_propro_p54
PMID: 12213596
Following virus replication, the generation of dsRNA activates the stress-induced MAPK pathway p38/JNK resulting in the AP-1 activation.
PMID: 12213596, 10626894, 10611240, 11846975
Virus infection or dsRNA treatment leads to the activation of the stress-activated members of the MAP kinase (MAP K) superfamily, namely the c-Jun amino terminal kinases (JNKs) and p38 proteins which are downstream of well defined stress-activated kinase cascades comprised of MKK4,7 and MKK3,6 respectively.
c136 cso30:c:InputProcess connector
c144 cso30:c:InputAssociation connector
c137 cso30:c:OutputProcess connector
p55_propro_p55
PMID: 12213596
Following virus replication, the generation of dsRNA activates the stress-induced MAPK pathway p38/JNK resulting in the AP-1 activation.
PMID: 12213596, 10626894, 10611240, 11846975
Virus infection or dsRNA treatment leads to the activation of the stress-activated members of the MAP kinase (MAP K) superfamily, namely the c-Jun amino terminal kinases (JNKs) and p38 proteins which are downstream of well defined stress-activated kinase cascades comprised of MKK4,7 and MKK3,6 respectively.
PMID: 12213596
Components of bacterial cell wall, such as LPS, activate TLR4 signaling, leading to cytokine production through the activation of JNK/p38 and IKK complex.
c138 cso30:c:InputProcess connector
c267 cso30:c:InputAssociation connector
c139 cso30:c:OutputProcess connector
p56_propro_p56
PMID: 12213596
Following virus replication, the generation of dsRNA activates the stress-induced MAPK pathway p38/JNK resulting in the AP-1 activation.
PMID: 12213596, 10626894, 10611240, 11846975
Virus infection or dsRNA treatment leads to the activation of the stress-activated members of the MAP kinase (MAP K) superfamily, namely the c-Jun amino terminal kinases (JNKs) and p38 proteins which are downstream of well defined stress-activated kinase cascades comprised of MKK4,7 and MKK3,6 respectively.
c140 cso30:c:InputProcess connector
c145 cso30:c:InputAssociation connector
c141 cso30:c:OutputProcess connector
p57_propro_p57
PMID: 12213596
Following virus replication, the generation of dsRNA activates the stress-induced MAPK pathway p38/JNK resulting in the AP-1 activation.
PMID: 12213596, 10626894, 10611240, 11846975
Virus infection or dsRNA treatment leads to the activation of the stress-activated members of the MAP kinase (MAP K) superfamily, namely the c-Jun amino terminal kinases (JNKs) and p38 proteins which are downstream of well defined stress-activated kinase cascades comprised of MKK4,7 and MKK3,6 respectively.
PMID: 12213596
Components of bacterial cell wall, such as LPS, activate TLR4 signaling, leading to cytokine production through the activation of JNK/p38 and IKK complex.
c142 cso30:c:InputProcess connector
c268 cso30:c:InputAssociation connector
c143 cso30:c:OutputProcess connector
p58_propro_p58
PMID: 12213596
Following virus replication, the generation of dsRNA activates the stress-induced MAPK pathway p38/JNK resulting in the AP-1 activation.
PMID: 12213596, 10626894, 10611240, 11846975
Virus infection or dsRNA treatment leads to the activation of the stress-activated members of the MAP kinase (MAP K) superfamily, namely the c-Jun amino terminal kinases (JNKs) and p38 proteins which are downstream of well defined stress-activated kinase cascades comprised of MKK4,7 and MKK3,6 respectively.
PMID: 12213596
Components of bacterial cell wall, such as LPS, activate TLR4 signaling, leading to cytokine production through the activation of JNK/p38 and IKK complex.
c148 cso30:c:InputProcess connector
c154 cso30:c:InputAssociation connector
c146 cso30:c:InputAssociation connector
c238 cso30:c:OutputProcess connector
p60_propro_p60
PMID: 12213596
Following virus replication, the generation of dsRNA activates the stress-induced MAPK pathway p38/JNK resulting in the AP-1 activation.
PMID: 12213596, 10626894, 10611240, 11846975
Virus infection or dsRNA treatment leads to the activation of the stress-activated members of the MAP kinase (MAP K) superfamily, namely the c-Jun amino terminal kinases (JNKs) and p38 proteins which are downstream of well defined stress-activated kinase cascades comprised of MKK4,7 and MKK3,6 respectively.
PMID: 12213596
Components of bacterial cell wall, such as LPS, activate TLR4 signaling, leading to cytokine production through the activation of JNK/p38 and IKK complex.
c152 cso30:c:InputProcess connector
c155 cso30:c:InputAssociation connector
c147 cso30:c:InputAssociation connector
c149 cso30:c:OutputProcess connector
p59_propro_p59
PMID: 12213596, 11401490
Indeed, PACT, a dsRNA-binding protein originally identified as an activator of PKR, was shown to enhance IRF-3 activation.
c150 cso30:c:InputProcess connector
c151 cso30:c:InputProcess connector
c156 cso30:c:OutputProcess connector
p62_propro_p62
PMID: 12213596
Interestingly, N protein physically interacts with IRF-3, implying that IRF-3 itself represents the molecule that detects the viral pathogen via nucleocapsid recognition.
c161 cso30:c:InputProcess connector
c162 cso30:c:InputProcess connector
c163 cso30:c:OutputProcess connector
p63_propro_p63
PMID: 12213596, 11907205
Indeed, a recent study has shown that the N nucleocapsid (N) protein of MeV induced IRF-3 activation via the induction of VAK.
c164 cso30:c:InputProcess connector
c166 cso30:c:InputAssociation connector
c165 cso30:c:OutputProcess connector
p64_propro_p64
PMID: 12213596
Following interaction with dsRNA, PKR becomes autophosphorylated and, in turn, phosphorylates a restricted number of substrates, the best characterized of which is the α subunit of eukaryotic protein synthesis initiation factor 2 (eIF2alpha).
c167 cso30:c:InputProcess connector
c168 cso30:c:InputProcess connector
c169 cso30:c:OutputProcess connector
p66_propro_p66
PMID: 12213596
Following interaction with dsRNA, PKR becomes autophosphorylated and, in turn, phosphorylates a restricted number of substrates, the best characterized of which is the alpha subunit of eukaryotic protein synthesis initiation factor 2 (eIF2alpha).
c173 cso30:c:InputProcess connector
c175 cso30:c:InputAssociation connector
c174 cso30:c:OutputProcess connector
p67_propro_p67
PMID: 12213596, 11585785
Phosphorylation of eIF2alpha on Ser 51 causes a dramatic inhibition of protein synthesis by sequestering the guanine nucleotide exchange factor eIF2B, a rate-limiting component of the translation machinery.
c176 cso30:c:InputProcess connector
c178 cso30:c:InputInhibitor connector
c177 cso30:c:OutputProcess connector
p68_propro_p68
PMID: 12213596, 11585785
Phosphorylation of eIF2alpha on Ser 51 causes a dramatic inhibition of protein synthesis by sequestering the guanine nucleotide exchange factor eIF2B, a rate-limiting component of the translation machinery.
c179 cso30:c:InputInhibitor connector
p69_propro_p69
PMID: 12213596, 10626894, 10848580
Another putative target of PKR is the IKKbeta subunit of the IKK complex that physically associates with PKR [20] and is believed to mediate the NF-kappaB activation in a manner that is independent of PKR kinase activity.
c180 cso30:c:InputProcess connector
c181 cso30:c:InputProcess connector
c182 cso30:c:OutputProcess connector
p70_propro_p70
PMID: 12213596, 10626894, 10848580
Another putative target of PKR is the IKKbeta subunit of the IKK complex that physically associates with PKR [20] and is believed to mediate the NF-kappaB activation in a manner that is independent of PKR kinase activity.
c183 cso30:c:InputProcess connector
c184 cso30:c:OutputProcess connector
p71_propro_p71
PMID: 12213596, 11607032
Activation of TLR-3 induces the activation of both MAPK and NF-kappaB pathways, independently of the adapter protein MyD88.
c186 cso30:c:InputProcess connector
c188 cso30:c:InputAssociation connector
c187 cso30:c:OutputProcess connector
p72_propro_p72
PMID: 12213596, 11477402, 11191641
Indeed, following PAMP interaction with the TLRs, the IKK and JNK/p38 pathways are activated resulting in the activation of NF-kappaB and AP-1 transcription factors which ultimately lead to cytokine production.
c192 cso30:c:InputAssociation connector
c189 cso30:c:OutputProcess connector
p73_propro_p73
PMID: 12213596, 11477402, 11191641
Indeed, following PAMP interaction with the TLRs, the IKK and JNK/p38 pathways are activated resulting in the activation of NF-kappaB and AP-1 transcription factors which ultimately lead to cytokine production.
c191 cso30:c:InputAssociation connector
c190 cso30:c:OutputProcess connector
p74_propro_p74
PMID: 12213596, 11477402, 11191641
Indeed, following PAMP interaction with the TLRs, the IKK and JNK/p38 pathways are activated resulting in the activation of NF-kappaB and AP-1 transcription factors which ultimately lead to cytokine production.
c194 cso30:c:InputAssociation connector
c193 cso30:c:OutputProcess connector
p75_propro_p75
PMID: 12213596
Activated TLRs associate with a cytoplasmic adapter molecule, MyD88, through the homophilic interaction between their TIR domains.
c195 cso30:c:InputProcess connector
c197 cso30:c:InputProcess connector
c196 cso30:c:OutputProcess connector
p76_propro_p76
PMID: 12213596
MyD88 interacts with the Ser/Thr kinase IRAK which subsequently activates the TRAF6 adapter.
c198 cso30:c:InputProcess connector
c200 cso30:c:InputProcess connector
c199 cso30:c:OutputProcess connector
p77_propro_p77
PMID: 12213596
MyD88 interacts with the Ser/Thr kinase IRAK which subsequently activates the TRAF6 adapter.
c201 cso30:c:InputProcess connector
c203 cso30:c:InputProcess connector
c202 cso30:c:OutputProcess connector
p78_propro_p78
PMID: 12213596
MyD88 interacts with the Ser/Thr kinase IRAK which subsequently activates the TRAF6 adapter.
c204 cso30:c:InputProcess connector
c205 cso30:c:OutputProcess connector
p79_propro_p79
PMID: 12213596
Components of bacterial cell wall, such as LPS, activate TLR4 signaling, leading to cytokine production through the activation of JNK/p38 and IKK complex.
c206 cso30:c:InputProcess connector
c210 cso30:c:InputAssociation connector
c207 cso30:c:OutputProcess connector
p80_propro_p80
PMID: 12213596
Components of bacterial cell wall, such as LPS, activate TLR4 signaling, leading to cytokine production through the activation of JNK/p38 and IKK complex.
c208 cso30:c:InputProcess connector
c211 cso30:c:InputAssociation connector
c209 cso30:c:OutputProcess connector
p81_propro_p81
PMID: 12213596
Components of bacterial cell wall, such as LPS, activate TLR4 signaling, leading to cytokine production through the activation of JNK/p38 and IKK complex.
c212 cso30:c:InputProcess connector
c214 cso30:c:InputAssociation connector
c213 cso30:c:OutputProcess connector
p82_propro_p82
PMID: 12213596, 11477402
Treatment of target cells with LPS activates multiple signaling pathways in addition to IKK/JNK/p38, such as protein kinase C, Src-type tyrosine kinases, and the phosphatidylinositol 3-kinase-protein kinase B pathways.
c215 cso30:c:InputProcess connector
c219 cso30:c:InputAssociation connector
c216 cso30:c:OutputProcess connector
p83_propro_p83
PMID: 12213596, 11477402
Treatment of target cells with LPS activates multiple signaling pathways in addition to IKK/JNK/p38, such as protein kinase C, Src-type tyrosine kinases, and the phosphatidylinositol 3-kinase-protein kinase B pathways.
c217 cso30:c:InputProcess connector
c220 cso30:c:InputAssociation connector
c218 cso30:c:OutputProcess connector
p84_propro_p84
PMID: 12213596, 11477402
Treatment of target cells with LPS activates multiple signaling pathways in addition to IKK/JNK/p38, such as protein kinase C, Src-type tyrosine kinases, and the phosphatidylinositol 3-kinase-protein kinase B pathways.
c221 cso30:c:InputProcess connector
c223 cso30:c:InputAssociation connector
c222 cso30:c:OutputProcess connector
p85_propro_p85
PMID: 12213596, 11698465
Phosphorylation of IRF-3 in response to LPS was demonstrated by Akira’s group.
PMID: 12213596, 10678979, 11896392
Treatment of murine macrophages with LPS also induces the production of IFNbeta, suggesting the activation of some IRF members by LPS [4 and 5] and also implying a role for ISGs in response to bacterial infection.
PMID: 1213596, 11854279
Another target gene, called UBP43 was also recently shown to be induced by LPS via IRF-3 in the murine macrophage-like cell line RAW 264.7.
c224 cso30:c:InputAssociation connector
c225 cso30:c:InputProcess connector
c226 cso30:c:OutputProcess connector
p86_propro_p86
PMID: 1213596, 11854279
Another target gene, called UBP43 was also recently shown to be induced by LPS via IRF-3 in the murine macrophage-like cell line RAW 264.7.
c228 cso30:c:InputAssociation connector
c227 cso30:c:OutputProcess connector
p87_propro_p87
PMID: 12213596, 11698465
Kim et al. [47] demonstrated that stress inducers and genotoxic agents such as DNA damaging agents doxorubicin and UV radiation stimulated IRF-3 phosphorylation, nuclear translocation, CBP association, and transcriptional activation of an IRF-3 responsive promoter.
PMID: 12213596, 11035028
Phosphorylation of IRF-3 by the DNA damaging agent doxorubicin, by the osmotic shock inducer sorbitol, the stress inducer anisomycin, the phorbol ester PMA and overexpression of the MAP KKK family members MEKK1 and Cot has also been observed with phosphorylation occurring at the N-terminal end, between aa 186198.
PMID: 12213596, 11035028
Indeed, as opposed to the observation made by Kim’s group, stress-inducers and DNA damaging agents failed to induce nuclear accumulation through CBP association or transcriptional activation of RANTES promoter.
c229 cso30:c:InputProcess connector
c231 cso30:c:InputAssociation connector
c230 cso30:c:OutputProcess connector
p88_propro_p88
PMID: 12213596, 10747925
In addition, a small molecule CG18 that stimulates MEKK1 activity activated the stress-mediated signaling pathway and stimulated the formation of the IFN-beta enhanceosome [48], including the activation of ATF-2/c-Jun, IRF-3, and NF-kappaB.
c232 cso30:c:InputProcess connector
c234 cso30:c:InputAssociation connector
c233 cso30:c:OutputProcess connector
p89_propro_p89
PMID: 12213596, 10747925
In addition, a small molecule CG18 that stimulates MEKK1 activity activated the stress-mediated signaling pathway and stimulated the formation of the IFN-beta enhanceosome [48], including the activation of ATF-2/c-Jun, IRF-3, and NF-kappaB.
PMID: 12213596
In these studies, MEKK1 activated IRF-3 through the JNK pathway but not through p38 or IKK pathways.
PMID: 12213596, 10747925
However, the phosphorylation site(s) targeted by the MEKK1-related pathway are distinct from the C-terminal sites, since the IRF-3 (5A) protein, in which the five phosphoacceptor sites in the C-terminal end (Ser 396 to Ser 405) were mutated to alanine (see Fig. 2), was still phosphorylated in response to CG18 and MEKK1.
c236 cso30:c:InputProcess connector
c240 cso30:c:InputAssociation connector
c237 cso30:c:OutputProcess connector
p23_propro_p23
PMID: 12213596
TRAF6 in turn activates the stress-related MAPK pathways JNK and p38, as well as the IKK complex leading to AP-1 and NF-kappaB activation respectively, and the induction of cytokines such as TNF-alpha and IL-6.
c59 cso30:c:InputProcess connector
c62 cso30:c:InputAssociation connector
c60 cso30:c:OutputProcess connector
p22_propro_p22
PMID: 12213596
TRAF6 in turn activates the stress-related MAPK pathways JNK and p38, as well as the IKK complex leading to AP-1 and NF-kappaB activation respectively, and the induction of cytokines such as TNF-alpha and IL-6.
c57 cso30:c:InputProcess connector
c61 cso30:c:InputAssociation connector
c58 cso30:c:OutputProcess connector
p90_propro_p90
PMID: 12213596, 10747925
In addition, a small molecule CG18 that stimulates MEKK1 activity activated the stress-mediated signaling pathway and stimulated the formation of the IFN-beta enhanceosome [48], including the activation of ATF-2/c-Jun, IRF-3, and NF-kappaB.
PMID: 12213596
In these studies, MEKK1 activated IRF-3 through the JNK pathway but not through p38 or IKK pathways.
PMID: 12213596
These experiments imply that MEKK1 can induce IRF-3 and ATF2/c-Jun through the JNK pathway and NF-kappaB through the IKK pathway, resulting in the integration of multiple signal transduction pathways leading to the proper assembly of the IFN-beta enhanceosome.
c71 cso30:c:InputProcess connector
c70 cso30:c:InputAssociation connector
c153 cso30:c:OutputProcess connector
p91_propro_p91
PMID: 12213596, 10747925
In addition, a small molecule CG18 that stimulates MEKK1 activity activated the stress-mediated signaling pathway and stimulated the formation of the IFN-beta enhanceosome [48], including the activation of ATF-2/c-Jun, IRF-3, and NF-kappaB.
PMID: 12213596
These experiments imply that MEKK1 can induce IRF-3 and ATF2/c-Jun through the JNK pathway and NF-kappaB through the IKK pathway, resulting in the integration of multiple signal transduction pathways leading to the proper assembly of the IFN-beta enhanceosome.
c239 cso30:c:InputProcess connector
c243 cso30:c:InputAssociation connector
c242 cso30:c:OutputProcess connector
p92_propro_p92
PMID: 12213596
These experiments imply that MEKK1 can induce IRF-3 and ATF2/c-Jun through the JNK pathway and NF-kappaB through the IKK pathway, resulting in the integration of multiple signal transduction pathways leading to the proper assembly of the IFN-beta enhanceosome.
c246 cso30:c:InputAssociation connector
c68 cso30:c:InputProcess connector
c69 cso30:c:OutputProcess connector
p93_propro_p93
PMID: 12213596, 11035028
Phosphorylation of IRF-3 by the DNA damaging agent doxorubicin, by the osmotic shock inducer sorbitol, the stress inducer anisomycin, the phorbol ester PMA and overexpression of the MAP KKK family members MEKK1 and Cot has also been observed with phosphorylation occurring at the N-terminal end, between aa 186198.
PMID: 12213596, 11035028
Indeed, as opposed to the observation made by Kim’s group, stress-inducers and DNA damaging agents failed to induce nuclear accumulation through CBP association or transcriptional activation of RANTES promoter.
c247 cso30:c:InputProcess connector
c250 cso30:c:InputAssociation connector
c248 cso30:c:OutputProcess connector
p94_propro_p94
PMID: 12213596, 11035028
Phosphorylation of IRF-3 by the DNA damaging agent doxorubicin, by the osmotic shock inducer sorbitol, the stress inducer anisomycin, the phorbol ester PMA and overexpression of the MAP KKK family members MEKK1 and Cot has also been observed with phosphorylation occurring at the N-terminal end, between aa 186198.
PMID: 12213596, 11035028
Indeed, as opposed to the observation made by Kim’s group, stress-inducers and DNA damaging agents failed to induce nuclear accumulation through CBP association or transcriptional activation of RANTES promoter.
c249 cso30:c:InputProcess connector
c251 cso30:c:InputAssociation connector
p95_propro_p95
PMID: 12213596, 11035028
Phosphorylation of IRF-3 by the DNA damaging agent doxorubicin, by the osmotic shock inducer sorbitol, the stress inducer anisomycin, the phorbol ester PMA and overexpression of the MAP KKK family members MEKK1 and Cot has also been observed with phosphorylation occurring at the N-terminal end, between aa 186198.
PMID: 12213596, 11035028
Indeed, as opposed to the observation made by Kim’s group, stress-inducers and DNA damaging agents failed to induce nuclear accumulation through CBP association or transcriptional activation of RANTES promoter.
c252 cso30:c:InputProcess connector
c254 cso30:c:InputAssociation connector
c253 cso30:c:OutputProcess connector
p96_propro_p96
PMID: 12213596, 11035028
Phosphorylation of IRF-3 by the DNA damaging agent doxorubicin, by the osmotic shock inducer sorbitol, the stress inducer anisomycin, the phorbol ester PMA and overexpression of the MAP KKK family members MEKK1 and Cot has also been observed with phosphorylation occurring at the N-terminal end, between aa 186198.
PMID: 12213596, 11035028
Indeed, as opposed to the observation made by Kim’s group, stress-inducers and DNA damaging agents failed to induce nuclear accumulation through CBP association or transcriptional activation of RANTES promoter.
c255 cso30:c:InputProcess connector
c257 cso30:c:InputAssociation connector
c256 cso30:c:OutputProcess connector
p97_propro_p97
PMID: 12213596
DNA-PK phosphorylates Thr 135 near the nuclear export sequence and may inhibit export of IRF-3 from the nucleus.
c258 cso30:c:InputProcess connector
c260 cso30:c:InputAssociation connector
c259 cso30:c:OutputProcess connector
p99_propro_p99
PMID: 12213596, 11698465
Recently, Akira’s group observed induction of the IP-10 gene with lipid A, the functional moiety of LPS, in MyD88-deficient peritoneal macrophages in which production of TNF-alpha and IL-6 in response to LPS is completely impaired.
c263 cso30:c:InputAssociation connector
c244 cso30:c:OutputProcess connector
p61_propro_p61
PMID: 12213596, 11401490
Indeed, PACT, a dsRNA-binding protein originally identified as an activator of PKR, was shown to enhance IRF-3 activation.
c157 cso30:c:InputProcess connector
c159 cso30:c:InputAssociation connector
c158 cso30:c:OutputProcess connector
p100_propro_p100
PMID: 12213596, 10626894, 10848580
Another putative target of PKR is the IKKbeta subunit of the IKK complex that physically associates with PKR [20] and is believed to mediate the NF-kappaB activation in a manner that is independent of PKR kinase activity.
c185 cso30:c:InputProcess connector
c264 cso30:c:InputAssociation connector
c262 cso30:c:OutputProcess connector
p101_propro_p101
PMID: 12213596
Components of bacterial cell wall, such as LPS, activate TLR4 signaling, leading to cytokine production through the activation of JNK/p38 and IKK complex.
c265 cso30:c:InputAssociation connector
c269 cso30:c:InputProcess connector
c270 cso30:c:OutputProcess connector
p102_propro_p102
PMID: 12213596
Components of bacterial cell wall, such as LPS, activate TLR4 signaling, leading to cytokine production through the activation of JNK/p38 and IKK complex.
c266 cso30:c:InputAssociation connector
c271 cso30:c:InputProcess connector
c272 cso30:c:OutputProcess connector
p25_propro_p25
PMID: 12213596
Virus infection results in the activation of multiple signaling cascades resulting in the phosphorylation of ATF-2, C-Jun, IRF-3, and NF-kapppaB.
PMID: 12213596
Following virus replication, the generation of dsRNA activates the stress-induced MAPK pathway p38/JNK resulting in the AP-1 activation.
PMID: 12213596
The heterodimers ATF-2/c-Jun are expressed as nuclear proteins that are activated by phosphorylation of their activation domains by p38/JNK.
PMID: 12213596, 10747925
In addition, a small molecule CG18 that stimulates MEKK1 activity activated the stress-mediated signaling pathway and stimulated the formation of the IFN-beta enhanceosome [48], including the activation of ATF-2/c-Jun, IRF-3, and NF-kappaB.
c241 cso30:c:InputAssociation connector
c66 cso30:c:InputProcess connector
c67 cso30:c:OutputProcess connector
p65_propro_p65
PMID: 12213596
Following interaction with dsRNA, PKR becomes autophosphorylated and, in turn, phosphorylates a restricted number of substrates, the best characterized of which is the alpha subunit of eukaryotic protein synthesis initiation factor 2 (eIF2alpha).
c170 cso30:c:InputProcess connector
c171 cso30:c:OutputProcess connector
c172 cso30:c:OutputProcess connector
p42_propro_p103
PMID: 12213596, 9566918, 9463386, 10082512
In addition, IRF-3 C-terminal phosphorylation is required for association with the histone acetyltransferase nuclear proteins CBP and p300 [10, 13 and 23] causing IRF-3, which normally shuttles into and out of the nucleus, to become predominantly nuclear.
PMID: 12213596
DNA-PK phosphorylates Thr 135 near the nuclear export sequence and may inhibit export of IRF-3 from the nucleus.
c97 cso30:c:InputProcess connector
c276 cso30:c:InputInhibitor connector
c274 cso30:c:OutputProcess connector
IRF-3_enti_MO000007694
IRF-3
IRF-3{p}_enti_MO000041456
IRF-3{p}
TLR4_enti_MO000019394
TLR4
TLRs_enti_MO000019395
TLRs
TLR3_enti_MO000019398
TLR3
TLR5_enti_MO000019399
TLR5
dsRNA:TLR3_enti_MO000041446
dsRNA:TLR3
TLR9_enti_MO000042012
TLR9
RANTES_enti_G010522
RANTES
IL15_enti_G012390
IL15
IFN-alpha1_enti_e5
IFN-alpha1
IFN-beta_enti_G010228
IFN-beta
IFN Type I_enti_MO000016658
IFN Type I
PKR_enti_MO000008179
PKR
dsRNA:PKR_enti_MO000022225
dsRNA:PKR
IKK-alpha:IKK-beta:IKK-gamma_enti_e6
IKK-alpha:IKK-beta:IKK-gamma
TLR2: TLR6_enti_e11
TLR2: TLR6
JNK_enti_MO000000023
JNK
p38_enti_MO000000022
p38
AP-1_enti_MO000000276
AP-1
DNA-PK_enti_MO000018334
DNA-PK
eIF-2alpha_enti_MO000022570
eIF-2alpha
MyD88_enti_MO000016573
MyD88
dsRNA_enti_MO000022224
dsRNA
LPS_enti_MO000016882
LPS
IRAK_enti_MO000000213
IRAK
TRAF6_enti_MO000000212
TRAF6
CD14_enti_MO000018132
CD14
PKR{p}_enti_e13
PKR{p}
TNF-alpha_enti_G010329
TNF-alpha
IFN Type 1 receptor: STAT1: STAT2: JAK_enti_e14
IFN Type 1 receptor: STAT1: STAT2: JAK
INF Type I: IFN Type 1 receptor: STAT1: STAT2: JAK_enti_e15
INF Type I: IFN Type 1 receptor: STAT1: STAT2: JAK
STAT1: STAT2 [activated}_enti_e16
STAT1: STAT2 [activated}
ISGF-3gamma: STAT1: STAT2 {activated}_enti_e17
ISGF-3gamma: STAT1: STAT2 {activated}
ISGF-3gamma_enti_MO000007758
ISGF-3gamma
ISRE_enti_e18
ISRE
ISGF-3gamma: STAT1: STAT2 {activated}_enti_e19
ISGF-3gamma: STAT1: STAT2 {activated}
ISGF-3gamma: STAT1: STAT2 {activated}: ISRE_enti_e20
ISGF-3gamma: STAT1: STAT2 {activated}: ISRE
OAS_enti_G010199
OAS
PKR_enti_e21
PKR
flagellin_enti_MO000022185
flagellin
LPS: TLR4_enti_e22
LPS: TLR4
RSV fusion protein_enti_e23
RSV fusion protein
RSV fusion protein: CD14: TLR4_enti_e24
RSV fusion protein: CD14: TLR4
Lp: TLR2: TLR6_enti_e25
Lp: TLR2: TLR6
peptidoglycanTLR2: TLR6_enti_e26
peptidoglycanTLR2: TLR6
Zymosan: TLR2: TLR6_enti_e27
Zymosan: TLR2: TLR6
flagellin: TLR5_enti_e28
flagellin: TLR5
CpG DNA_enti_e29
CpG DNA
CpG DNA: TLR9_enti_e30
CpG DNA: TLR9
TLR ligand_enti_e31
TLR ligand
TLR ligand: TLR_enti_e32
TLR ligand: TLR
TLR ligand: TLR: MyD88_enti_e33
TLR ligand: TLR: MyD88
Lp_enti_MO000017793
Lp
peptidoglycan_enti_e34
peptidoglycan
Zymosan_enti_e35
Zymosan
TLR ligand: TLR: MyD88: IRAK_enti_e36
TLR ligand: TLR: MyD88: IRAK
TLR ligand: TLR: MyD88: IRAK: TRAF6_enti_e37
TLR ligand: TLR: MyD88: IRAK: TRAF6
TLR ligand: TLR: MyD88: IRAK: TRAF6 {activated}_enti_e38
TLR ligand: TLR: MyD88: IRAK: TRAF6 {activated}
IKK-alpha:IKK-beta:IKK-gamma {activated}_enti_e41
IKK-alpha:IKK-beta:IKK-gamma {activated}
p50:RelA-p65:IkappaB-alpha{p}_enti_MO000000254
p50:RelA-p65:IkappaB-alpha{p}
p50:RelA-p65:IkappaB-alpha_enti_MO000038724
p50:RelA-p65:IkappaB-alpha
p50:RelA-p65_enti_MO000016632
p50:RelA-p65
p50:RelA-p65_enti_e44
p50:RelA-p65
IL-6_enti_G010262
IL-6
protein remnants_enti_MO000019479
PMID: 12213596, 10837071
Phosphorylation triggers a signal that induces ubiquitin-dependent, proteasome-mediated degradation of IkappaB-alpha, and subsequent nuclear translocation of the NF-kappaB dimers.
protein remnants
p50:RelA-p65:IkappaB-alpha{p} {ub}_enti_e45
p50:RelA-p65:IkappaB-alpha{p} {ub}
AP-1 {activated}_enti_e46
AP-1 {activated}
poly I: C_enti_e47
poly I: C
poly I: C: TLR3_enti_e48
poly I: C: TLR3
ISG_enti_e63
ISG
IRF-3: IRF-3 {p}_enti_e64
IRF-3: IRF-3 {p}
p300: CBP: IRF-3: IRF-3 {p}_enti_e65
p300: CBP: IRF-3: IRF-3 {p}
p300: CBP_enti_e66
p300: CBP
p300: CBP: IRF-3: IRF-3 {p} {nucleus}_enti_e67
p300: CBP: IRF-3: IRF-3 {p} {nucleus}
p300: CBP: IRF-3: IRF-3 {p} {nucleus}: ISRE_enti_e68
p300: CBP: IRF-3: IRF-3 {p} {nucleus}: ISRE
ISG56_enti_e69
ISG56
ISG56_enti_e70
ISG56
ISG56: ISG-3gamma_enti_e71
ISG56: ISG-3gamma
VAK_enti_e72
VAK
VAK {activated}_enti_e73
VAK {activated}
PACT_enti_MO000022533
PACT
MKK4_enti_MO000016917
MKK4
MKK7_enti_MO000016916
MKK7
MKK4 {activated}_enti_e74
MKK4 {activated}
MKK3_enti_MO000016966
MKK3
MKK6_enti_MO000019005
MKK6
MKK7 {activated}_enti_e75
MKK7 {activated}
MKK3 {activated}_enti_e76
MKK3 {activated}
MKK6 {activated}_enti_e77
MKK6 {activated}
dsRNA: PACT_enti_e78
dsRNA: PACT
N protein of MeV_enti_e79
N protein of MeV
N protein of MeV: IRF-3_enti_e80
N protein of MeV: IRF-3
eIF-2alpha {p}_enti_e81
eIF-2alpha {p}
eIF-2beta_enti_MO000068430
eIF-2beta
eIF-2beta {activated}_enti_e82
eIF-2beta {activated}
IKK-alpha:IKK-beta:IKK-gamma: PKR{p}_enti_e83
IKK-alpha:IKK-beta:IKK-gamma: PKR{p}
cytokines_enti_e84
cytokines
cytokines_enti_MO000019387
cytokines
LPS: TLR4: MyD88_enti_e85
LPS: TLR4: MyD88
LPS: TLR4: MyD88: IRAK_enti_e86
LPS: TLR4: MyD88: IRAK
LPS: TLR4: MyD88: IRAK: TRAF6_enti_e87
LPS: TLR4: MyD88: IRAK: TRAF6
LPS: TLR4: MyD88: IRAK: TRAF6 {activated}_enti_e88
LPS: TLR4: MyD88: IRAK: TRAF6 {activated}
PKC_enti_MO000000104
PKC
PKC {activated}_enti_e89
PKC {activated}
Src family_enti_MO000000136
Src family
Src family {activated}_enti_e90
Src family {activated}
PI3K family_enti_MO000017608
PI3K family
PI3K family_enti_e91
PI3K family
USG43_enti_e92
USG43
doxorubicin_enti_e93
doxorubicin
CG18_enti_e94
CG18
MEKK1_enti_MO000000047
MEKK1
MEKK1 {activated}_enti_e95
MEKK1 {activated}
JNK {p}_enti_e96
JNK {p}
p38{p}_enti_e40
p38{p}
IRF{p} { N terimal}_enti_e39
IRF{p} { N terimal}
sorbitol_enti_e97
sorbitol
anisomycin_enti_e98
anisomycin
PMA_enti_e99
PMA
IRF-3{pT135}_enti_e100
IRF-3{pT135}
lipid A_enti_e102
lipid A
IP-10_enti_e12
IP-10
PKR {activated}_enti_e101
PKR {activated}
IKK-alpha:IKK-beta {activated}:IKK-gamma: PKR{p}_enti_e103
IKK-alpha:IKK-beta {activated}:IKK-gamma: PKR{p}
c-Jun: ATF2_enti_e104
c-Jun: ATF2
c-Jun {p}: ATF2_enti_e105
c-Jun {p}: ATF2
c-Jun: ATF2 {p}_enti_e106
c-Jun: ATF2 {p}
IP-10_enti_e42
IP-10