_enti_e7
_enti_e1
_enti_e2
_enti_e4
_enti_e3
g1_fact_g2
g1_fact_g1
g1_fact_g5
g1_fact_g14
g1_fact_g4
p1_propro_p1
PMID: 18585455,12796777,12791997
NOD1 activity is triggered by g-Dglutamyl-
meso-diaminopimelic acid (meso-DAP) 1), which is unique to PGN structures from all
Gram-negative bacteria and certain Gram-positive bacteria,
including the genus Listeria and Bacillus
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 18585455,12527755,12514169
In contrast, NOD2 is activated by muramyl dipeptide
(MDP), a peptidogylcan motif present in all
Gram-positive and Gram-negative bacteria
c4 cso30:c:InputProcess connector
c5 cso30:c:InputProcess connector
c6 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 18585455
Upon ligand recognition, NOD1 and NOD2 undergo conformational
changes and selfoligomerization.
c7 cso30:c:InputProcess connector
c8 cso30:c:OutputProcess connector
p3_propro_p4
PMID: 18585455
Upon ligand recognition, NOD1 and NOD2 undergo conformational
changes and selfoligomerization.
c9 cso30:c:InputProcess connector
c10 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 18585455,10880512,11463746,17277144,17579072
This is followed by the recruitment and activation of the serine
threonine kinase RICK (RIP2), essential for the activation
of NF-kB and MAPKs
c11 cso30:c:InputProcess connector
c12 cso30:c:InputProcess connector
c13 cso30:c:OutputProcess connector
p5_propro_p6
PMID: 18585455,10880512,11463746,17277144,17579072
This is followed by the recruitment and activation of the serine
threonine kinase RICK (RIP2), essential for the activation
of NF-kB and MAPKs
c14 cso30:c:InputProcess connector
c16 cso30:c:InputProcess connector
c15 cso30:c:OutputProcess connector
p7_propro_p7
PMID: 18585455
Although, both NOD1 and NOD2 induce similar K63-linked ubiquitination of RICK for NF-kB activation,
Nod2-signaling appears to preferentially utilize the E3
ligase TRAF6, whereas TRAF2 and TRAF5 were shown
to be important for NOD1-mediated signaling.
c17 cso30:c:InputProcess connector
c18 cso30:c:InputAssociation connector
c19 cso30:c:OutputProcess connector
p7_propro_p8
PMID: 18585455
Although, both NOD1 and NOD2 induce similar K63-linked ubiquitination of RICK for NF-kB activation,
Nod2-signaling appears to preferentially utilize the E3
ligase TRAF6, whereas TRAF2 and TRAF5 were shown
to be important for NOD1-mediated signaling.
c20 cso30:c:InputProcess connector
c21 cso30:c:InputAssociation connector
c22 cso30:c:OutputProcess connector
p7_propro_p9
PMID: 18585455
Although, both NOD1 and NOD2 induce similar K63-linked ubiquitination of RICK for NF-kB activation,
Nod2-signaling appears to preferentially utilize the E3
ligase TRAF6, whereas TRAF2 and TRAF5 were shown
to be important for NOD1-mediated signaling.
c23 cso30:c:InputProcess connector
c24 cso30:c:InputAssociation connector
c25 cso30:c:OutputProcess connector
p10_propro_p10
PMID: 18585455
K63-linked regulatory ubiquitination of RICK leads to the
recruitment of TAK1.
PMID: 18585455,18079694,18342009
Similar to
TLR signaling, recent studies have demonstrated that
K63-linked regulatory ubiquitination of RICK is essential
for the recruitment of TAK1
c26 cso30:c:InputProcess connector
c27 cso30:c:InputProcess connector
c28 cso30:c:OutputProcess connector
p10_propro_p11
PMID: 18585455
K63-linked regulatory ubiquitination of RICK leads to the
recruitment of TAK1.
PMID: 18585455,18079694,18342009
Similar to
TLR signaling, recent studies have demonstrated that
K63-linked regulatory ubiquitination of RICK is essential
for the recruitment of TAK1
c29 cso30:c:InputProcess connector
c30 cso30:c:InputProcess connector
c31 cso30:c:OutputProcess connector
p12_propro_p12
PMID: 18585455
The activation and recruitment of TAK1 complex to
RICK further recruits the IKK complex
c32 cso30:c:InputProcess connector
c33 cso30:c:InputProcess connector
c34 cso30:c:OutputProcess connector
p12_propro_p13
PMID: 18585455
The activation and recruitment of TAK1 complex to
RICK further recruits the IKK complex
c35 cso30:c:InputProcess connector
c36 cso30:c:InputProcess connector
c37 cso30:c:OutputProcess connector
p14_propro_p14
PMID: 18585455
The interaction between RICK
and NEMO ultimately results in the activation of IKKs and MKK by TAK1
c38 cso30:c:InputProcess connector
c39 cso30:c:OutputProcess connector
p14_propro_p15
PMID: 18585455
The interaction between RICK
and NEMO ultimately results in the activation of IKKs and MKK by TAK1
c40 cso30:c:InputProcess connector
c41 cso30:c:OutputProcess connector
p14_propro_p16
PMID: 18585455
The interaction between RICK
and NEMO ultimately results in the activation of IKKs and MKK by TAK1
PMID: 18585455,10880512,11463746,17277144,17579072
This is followed
by the recruitment and activation of the serine
threonine kinase RICK (RIP2), essential for the activation
of NF-kB and MAPKs
c42 cso30:c:InputAssociation connector
c47 cso30:c:InputProcess connector
c55 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 18585455
Recently it was demonstrated that
ectopically expressed CARD9, an essential protein in
antifungal responses and TLR signaling, interacts with
NOD2 after challenge with L. monocytogenes.
c48 cso30:c:InputProcess connector
c49 cso30:c:InputProcess connector
c51 cso30:c:InputAssociation connector
c50 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 18585455,10880512,11463746,17277144,17579072
This is followed by the recruitment and activation of the serine
threonine kinase RICK (RIP2), essential for the activation
of NF-kB and MAPKs
c52 cso30:c:InputAssociation connector
c53 cso30:c:InputProcess connector
c54 cso30:c:OutputProcess connector
p19_propro_p20
PMID: 18585455,10880512,11463746,17277144,17579072
This is followed by the recruitment and activation of the serine
threonine kinase RICK (RIP2), essential for the activation
of NF-kB and MAPKs
c43 cso30:c:InputAssociation connector
c44 cso30:c:InputProcess connector
c46 cso30:c:OutputProcess connector
p14_propro_p21
PMID: 18585455
The interaction between RICK
and NEMO ultimately results in the activation of IKKs and MKK by TAK1
PMID: 18585455,10880512,11463746,17277144,17579072
This is followed
by the recruitment and activation of the serine
threonine kinase RICK (RIP2), essential for the activation
of NF-kB and MAPKs
c56 cso30:c:InputAssociation connector
c57 cso30:c:InputProcess connector
c58 cso30:c:OutputProcess connector
p14_propro_p22
PMID: 18585455
The interaction between RICK
and NEMO ultimately results in the activation of IKKs and MKK by TAK1
PMID: 18585455,10880512,11463746,17277144,17579072
This is followed
by the recruitment and activation of the serine
threonine kinase RICK (RIP2), essential for the activation
of NF-kB and MAPKs
c59 cso30:c:InputAssociation connector
c60 cso30:c:InputProcess connector
c61 cso30:c:OutputProcess connector
p14_propro_p23
PMID: 18585455
The interaction between RICK
and NEMO ultimately results in the activation of IKKs and MKK by TAK1
PMID: 18585455,10880512,11463746,17277144,17579072
This is followed
by the recruitment and activation of the serine
threonine kinase RICK (RIP2), essential for the activation
of NF-kB and MAPKs
c62 cso30:c:InputAssociation connector
c63 cso30:c:InputProcess connector
c64 cso30:c:OutputProcess connector
p14_propro_p24
PMID: 18585455
The interaction between RICK
and NEMO ultimately results in the activation of IKKs and MKK by TAK1
PMID: 18585455,10880512,11463746,17277144,17579072
This is followed
by the recruitment and activation of the serine
threonine kinase RICK (RIP2), essential for the activation
of NF-kB and MAPKs
c65 cso30:c:InputAssociation connector
c66 cso30:c:InputProcess connector
c67 cso30:c:OutputProcess connector
p14_propro_p25
PMID: 18585455
The interaction between RICK
and NEMO ultimately results in the activation of IKKs and MKK by TAK1
PMID: 18585455,10880512,11463746,17277144,17579072
This is followed
by the recruitment and activation of the serine
threonine kinase RICK (RIP2), essential for the activation
of NF-kB and MAPKs
c68 cso30:c:InputAssociation connector
c69 cso30:c:InputProcess connector
c70 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 18585455,18079694,18342009
As
in the case of TLRs, this modification can be removed by
the deubiquitinating enzyme A20, thus dampening
NOD1/NOD2-induced NF-kB activation
c45 cso30:c:InputProcess connector
c71 cso30:c:InputAssociation connector
c72 cso30:c:OutputProcess connector
p17_propro_p26
PMID: 18585455,18079694,18342009
As
in the case of TLRs, this modification can be removed by
the deubiquitinating enzyme A20, thus dampening
NOD1/NOD2-induced NF-kB activation
c73 cso30:c:InputProcess connector
c75 cso30:c:InputAssociation connector
c74 cso30:c:OutputProcess connector
p27_propro_p27
PMID: 18585455,17187069
Furthermore,
CARD9-deficient macrophages exhibited impaired
phosphorylation of p38 after MDP stimulation,
suggesting that CARD9 is another essential intermediate
in the NOD2-signaling cascade that acts downstream of
TAK1
c76 cso30:c:InputProcess connector
c78 cso30:c:InputAssociation connector
c77 cso30:c:OutputProcess connector
p28_propro_p28
PMID: 18585455,17433728
TLR-mediated NF-kB
is required for the production of pro-IL-1b while the
cleavage of pro-IL-1b into its biologically active form is
dependent on NLR-mediated caspase-1 activation
c79 cso30:c:InputProcess connector
c81 cso30:c:InputAssociation connector
c80 cso30:c:OutputProcess connector
p29_propro_p29
PMID: 18585455,17433728
TLR-mediated NF-kB
is required for the production of pro-IL-1b while the
cleavage of pro-IL-1b into its biologically active form is
dependent on NLR-mediated caspase-1 activation
c82 cso30:c:InputAssociation connector
c83 cso30:c:OutputProcess connector
p30_propro_p30
PMID: 18585455,17433728
TLR-mediated NF-kB
is required for the production of pro-IL-1b while the
cleavage of pro-IL-1b into its biologically active form is
dependent on NLR-mediated caspase-1 activation
c84 cso30:c:InputProcess connector
c89 cso30:c:InputAssociation connector
c85 cso30:c:OutputProcess connector
p31_propro_p31
PMID: 18585455,17433728
TLR-mediated NF-kB
is required for the production of pro-IL-1b while the
cleavage of pro-IL-1b into its biologically active form is
dependent on NLR-mediated caspase-1 activation
c87 cso30:c:InputProcess connector
c86 cso30:c:InputAssociation connector
c88 cso30:c:OutputProcess connector
p31_propro_p32
PMID: 18585455,17433728
TLR-mediated NF-kB
is required for the production of pro-IL-1b while the
cleavage of pro-IL-1b into its biologically active form is
dependent on NLR-mediated caspase-1 activation
c91 cso30:c:InputProcess connector
c99 cso30:c:InputAssociation connector
c92 cso30:c:OutputProcess connector
p33_propro_p33
PMID: 18585455
NLRC4 has been demonstrated to
mediate caspase-1 activation, independent of TLR5,
following cytosolic delivery of flagellin.
PMID: 18585455
Various intracellular
bacteria have the ability to activate caspase-1
in a NLRC4-dependent manner
c93 cso30:c:InputAssociation connector
c94 cso30:c:InputProcess connector
c95 cso30:c:OutputProcess connector
p34_propro_p34
PMID: 18585455
NLRP3 mediates activation of caspase-1 in
response to a variety of structurally unrelated stimuli,
not limiting to those of bacterial origin.
c96 cso30:c:InputAssociation connector
c97 cso30:c:InputProcess connector
c98 cso30:c:OutputProcess connector
Nod1_enti_MO000020434
Nod1
Nod2_enti_MO000020461
Nod2
PGN_enti_MO000042032
PGN
Nod1:PGN_enti_e5
Nod1:PGN
Nod2:PGN_enti_e6
Nod2:PGN
Nod1{oligo}:PGN_enti_e11
Nod1{oligo}:PGN
Nod2{oligo}:PGN_enti_e12
Nod2{oligo}:PGN
RIP2_enti_MO000017949
RIP2
Nod1{oligo}:PGN:RIP2_enti_e13
Nod1{oligo}:PGN:RIP2
Nod2{oligo}:PGN:RIP2_enti_e14
Nod2{oligo}:PGN:RIP2
TRAF6_enti_MO000000212
TRAF6
TRAF2_enti_MO000000209
TRAF2
TRAF5_enti_MO000016965
TRAF5
Nod1{oligo}:PGN:RIP2{ub}_enti_e15
Nod1{oligo}:PGN:RIP2{ub}
Nod2{oligo}:PGN:RIP2{ub}_enti_e16
Nod2{oligo}:PGN:RIP2{ub}
TAK1_enti_MO000016574
TAK1
Nod1{oligo}:PGN:RIP2{ub}:TAK1_enti_e17
Nod1{oligo}:PGN:RIP2{ub}:TAK1
Nod2{oligo}:PGN:RIP2{ub}:TAK1_enti_e18
Nod2{oligo}:PGN:RIP2{ub}:TAK1
IKK-alpha:IKK-beta:Nemo_enti_MO000000210
IKK-alpha:IKK-beta:Nemo
Nod1{oligo}:PGN:RIP2{ub}:TAK1:IKK_enti_e29
Nod1{oligo}:PGN:RIP2{ub}:TAK1:IKK
Nod2{oligo}:PGN:RIP2{ub}:TAK1:IKK_enti_e30
Nod2{oligo}:PGN:RIP2{ub}:TAK1:IKK
Nod1{oligo}:PGN:RIP2{ub}:TAK1:IKK{active}_enti_e31
Nod1{oligo}:PGN:RIP2{ub}:TAK1:IKK{active}
Nod2{oligo}:PGN:RIP2{ub}:TAK1:IKK{active}_enti_e32
Nod2{oligo}:PGN:RIP2{ub}:TAK1:IKK{active}
CARD9_enti_MO000044196
CARD9
Nod2:CARD9_enti_e35
Nod2:CARD9
L.momocytogenes_enti_e36
L.momocytogenes
NF-kappaB_enti_MO000000058
NF-kappaB
NF-kappaB{active}_enti_e37
NF-kappaB{active}
p38_enti_MO000000022
p38
JNK_enti_MO000000023
JNK
ERK_enti_MO000000011
ERK
p38{active}_enti_e33
p38{active}
JNK{active}_enti_e34
JNK{active}
ERK{active}_enti_e38
ERK{active}
A20_enti_MO000016591
A20
p38{p}_enti_e39
p38{p}
TLR_enti_e40
TLR
proIL-1beta_enti_MO000019449
proIL-1beta
IL-1beta_enti_MO000016597
IL-1beta
Caspase-1_enti_MO000016828
Caspase-1
Caspase-1{active}_enti_e41
Caspase-1{active}
NLRC4_enti_e42
NLRC4
NLRP3_enti_e43
NLRP3