Entity
JNK
--
MO000000023
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m30
10
infinite
0
TRANSPATH | MO000000023 |
--
TNF-alpha
--
MO000000289
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m230
10
infinite
0
InterPro | IPR003636 |
TRANSPATH | MO000000289 |
--
PKCepsilon
--
MO000016645
cso30:c:Protein
cso30:i:CC_CellComponent
--
--
csml-variable:Double
m1629
10
infinite
0
InterPro | IPR000719 |
TRANSPATH | MO000016645 |
--
IFNgamma
--
MO000016665
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m1639
10
infinite
0
InterPro | IPR002069 |
TRANSPATH | MO000016665 |
--
MKP-1
--
MO000016814
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m1752
10
infinite
0
InterPro | IPR000340 |
TRANSPATH | MO000016814 |
--
glucocorticoids
--
MO000021732
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m6069
10
infinite
0
TRANSPATH | MO000021732 |
--
--
e1
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane
--
--
--
csml-variable:Double
m1
0
infinite
0
--
--
e10
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cytosol
--
--
--
csml-variable:Double
m10
0
infinite
0
--
differentiation genes
--
e11
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
--
--
csml-variable:Double
m11
0
infinite
0
--
apoptosis
--
e12
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
--
--
csml-variable:Double
m12
0
infinite
0
--
proinflammatory cytokines
--
e13
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
--
--
csml-variable:Double
m13
0
infinite
0
--
MAP3K
--
e14
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m14
0
infinite
0
--
MAP2K{p}
--
e15
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m15
0
infinite
0
--
MAP2K
--
e16
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m16
0
infinite
0
--
MAPK
--
e17
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m17
0
infinite
0
--
MAPK{p}
--
e18
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m18
0
infinite
0
--
AP-1{p}
--
e19
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m19
0
infinite
0
--
--
e2
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m2
0
infinite
0
--
TLR
--
e20
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m20
0
infinite
0
--
MKP-1
--
e21
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
--
csml-variable:Double
m21
0
infinite
0
--
TLR:MyD88
--
e22
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m22
0
infinite
0
--
TLR:TRIF
--
e23
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m23
0
infinite
0
--
PKCepsilon{active}
--
e25
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m26
10
infinite
0
InterPro | IPR000719 |
TRANSPATH | MO000016645 |
--
JNK{active}
--
e28
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m32
10
infinite
0
TRANSPATH | MO000000023 |
--
--
e3
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
--
csml-variable:Double
m3
0
infinite
0
--
SCF ubiquitin liagse
--
e30
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m34
0
infinite
0
--
MKP-1{p}:SCF ubiquitin liagse
--
e31
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m35
0
infinite
0
--
degradants
--
e32
cso30:c:EntityBiological
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m36
0
infinite
0
--
ROS
--
e33
cso30:c:SmallMolecule
cso30:i:CC_Cytosol
--
csml-variable:Double
m38
0
infinite
0
--
NOS2
--
e34
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
--
--
csml-variable:Double
m39
0
infinite
0
--
MKP-1:p300
--
e36
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m42
0
infinite
0
--
MKP-1{Ac}:p38{p}
--
e39
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m45
0
infinite
0
--
--
e4
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m4
0
infinite
0
--
MKP-1{Ac}:p38
--
e40
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m46
0
infinite
0
--
HDAC inhibitors
--
e5
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m5
0
infinite
0
--
--
e50
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearEnvelopeLumen
--
--
--
csml-variable:Double
m50
0
infinite
0
--
--
e51
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearPore
--
--
--
csml-variable:Double
m51
0
infinite
0
--
--
e52
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearInnerMembrane
--
--
--
csml-variable:Double
m52
0
infinite
0
--
--
e53
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearLumen
--
--
--
csml-variable:Double
m53
0
infinite
0
--
--
e54
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearOuterMembrane
--
--
--
csml-variable:Double
m54
0
infinite
0
--
--
e55
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleus
--
--
--
csml-variable:Double
m55
0
infinite
0
--
--
e56
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleoplasm
--
--
--
csml-variable:Double
m56
0
infinite
0
--
--
e57
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearBody
--
--
--
csml-variable:Double
m57
0
infinite
0
--
--
e58
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleolus
--
--
--
csml-variable:Double
m58
0
infinite
0
--
--
e59
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearEnvelope
--
--
--
csml-variable:Double
m59
0
infinite
0
--
cell growth arrest genes
--
e6
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
--
--
csml-variable:Double
m6
0
infinite
0
--
--
e60
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Chromatin
--
--
--
csml-variable:Double
m60
0
infinite
0
--
--
e61
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearChromosome
--
--
--
csml-variable:Double
m61
0
infinite
0
--
--
e62
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearCentromere
--
--
--
csml-variable:Double
m62
0
infinite
0
--
--
e7
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell
--
--
--
csml-variable:Double
m7
0
infinite
0
--
--
e8
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell_WithoutCellWall_
--
--
--
csml-variable:Double
m8
0
infinite
0
--
--
e9
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cytoplasm
--
--
--
csml-variable:Double
m9
0
infinite
0
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
m5*0.1
nodelay
--
0
PMID: 18922786,11902574 HDAC inhibitors induce the expression of a subset of genes involved in cell growth arrest, differentiation, and apoptosis, which accounts for the antitumor effects of these compounds
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c18 : 1
stoichiometry:c22 : 1
stoichiometry:c23 : 1
m20*m1572*0.1
nodelay
--
0
PMID: 18922786,16497588 The signals involved in TLR-induced expression of MKP-1 are beginning to be defined. Stimulation of TLRs activates two distinct pathways that are mediated by the adaptor proteins myeloid differentiation marker 88 (MyD88) and TRIF [Toll-IL-1 receptor (TIR) domain-containing adapter-inducing interferon-beta (IFN-beta)], respectively
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c25 : 1
stoichiometry:c26 : 1
stoichiometry:c27 : 1
m20*m18998*0.1
nodelay
--
0
PMID: 18922786,16497588 The signals involved in TLR-induced expression of MKP-1 are beginning to be defined. Stimulation of TLRs activates two distinct pathways that are mediated by the adaptor proteins myeloid differentiation marker 88 (MyD88) and TRIF [Toll-IL-1 receptor (TIR) domain-containing adapter-inducing interferon-beta (IFN-beta)], respectively
p8
p12
cso30:i:ME_GeneExpression
cso30:i:CC_Nucleoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c28 : 1
stoichiometry:c62 : 1
stoichiometry:c29 : 1
m23*0.1
nodelay
--
0
PMID: 18922786,16461893,16380513,12444149,15590669,16978838 In macrophages responding to TLR stimulation, there is a strong and rapid induction of MKP-1 mRNA and increase in MKP-1 protein abundance, peaking at 1 hour after stimulation PMID: 18922786,16461893 TLR-induced expression of MKP-1 is reduced in mice lacking either MyD88 or TRIF compared to that in wildtype mice, suggesting that MKP-1 is induced through both MyD88- and TRIF-dependent pathways in response to activation of TLRs PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-gamma) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation
p13
p13
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c31 : 1
stoichiometry:c30 : 1
stoichiometry:c32 : 1
m24*m22*0.1
nodelay
--
0
PMID: 18922786,16709817,10604989 In addition, a signaling pathway consisting of the MAP3K Raf-1 and protein kinase C epsilon (PKCepsilon) is required for TLR-induced expression of MKP-1 in macrophages
p13
p14
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c33 : 1
stoichiometry:c34 : 1
stoichiometry:c35 : 1
m25*m1629*0.1
nodelay
--
0
PMID: 18922786,16709817,10604989 In addition, a signaling pathway consisting of the MAP3K Raf-1 and protein kinase C epsilon (PKCepsilon) is required for TLR-induced expression of MKP-1 in macrophages
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c36 : 1
stoichiometry:c66 : 1
stoichiometry:c37 : 1
m26*0.1
nodelay
--
0
PMID: 18922786,16709817,10604989 In addition, a signaling pathway consisting of the MAP3K Raf-1 and protein kinase C epsilon (PKCepsilon) is required for TLR-induced expression of MKP-1 in macrophages PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-¦Ã) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation
p16
p16
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c38 : 1
stoichiometry:c39 : 1
stoichiometry:c96 : 1
stoichiometry:c40 : 1
m22*m27*0.1
nodelay
--
0
PMID: 18922786,12444149,16978838,17337450 Furthermore, ERK, JNK, and p38 MAPK have all been suggested to facilitate TLR-induced expression of MKP-1 PMID: 18922786 They found that HDAC inhibitors reduced the activation of p38 MAPK and ERK, but not JNK or the NF-KappaB pathway.
p17
p17
cso30:i:ME_GeneExpression
cso30:i:CC_Nucleoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c65 : 1
stoichiometry:c42 : 1
m28*0.1
nodelay
--
0
PMID: 18922786,12444149,16978838,17337450 Furthermore, ERK, JNK, and p38 MAPK have all been suggested to facilitate TLR-induced expression of MKP-1 PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-gamma) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation
p17
p18
cso30:i:ME_GeneExpression
cso30:i:CC_Nucleoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c46 : 1
stoichiometry:c64 : 1
stoichiometry:c47 : 1
m31*0.1
nodelay
--
0
PMID: 18922786,12444149,16978838,17337450 Furthermore, ERK, JNK, and p38 MAPK have all been suggested to facilitate TLR-induced expression of MKP-1 PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-gamma) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation
p16
p19
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c43 : 1
stoichiometry:c44 : 1
stoichiometry:c97 : 1
stoichiometry:c45 : 1
m22*m29*0.1
nodelay
--
0
PMID: 18922786,12444149,16978838,17337450 Furthermore, ERK, JNK, and p38 MAPK have all been suggested to facilitate TLR-induced expression of MKP-1 PMID: 18922786 They found that HDAC inhibitors reduced the activation of p38 MAPK and ERK, but not JNK or the NF-KappaB pathway.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c3 : 1
stoichiometry:c4 : 1
m5*0.1
nodelay
--
0
PMID: 18922786,11902574 HDAC inhibitors induce the expression of a subset of genes involved in cell growth arrest, differentiation, and apoptosis, which accounts for the antitumor effects of these compounds
p16
p20
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c48 : 1
stoichiometry:c49 : 1
stoichiometry:c50 : 1
m22*m30*0.1
nodelay
--
0
PMID: 18922786,12444149,16978838,17337450 Furthermore, ERK, JNK, and p38 MAPK have all been suggested to facilitate TLR-induced expression of MKP-1
p17
p21
cso30:i:ME_GeneExpression
cso30:i:CC_Nucleoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c51 : 1
stoichiometry:c63 : 1
stoichiometry:c52 : 1
m32*0.1
nodelay
--
0
PMID: 18922786,12444149,16978838,17337450 Furthermore, ERK, JNK, and p38 MAPK have all been suggested to facilitate TLR-induced expression of MKP-1 PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-gamma) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation
p22
p22
cso30:i:ME_GeneExpression
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c67 : 1
stoichiometry:c54 : 1
m6069*0.1
nodelay
--
0
PMID: 18922786 MKP-1 is also induced by multiple immunosuppressive agents, including glucocorticoids and anti-inflammatory cytokines, and this induction partially mediates the inhibitory effects of these agents on MAPK activation and inflammation PMID: 18922786 Figure 1A PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-gamma) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation
p23
p23
cso30:i:ME_GeneExpression
cso30:i:CC_NuclearChromosome
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c55 : 1
stoichiometry:c59 : 1
stoichiometry:c56 : 1
m1746*0.1
nodelay
--
0
PMID: 18922786,16184516,11842088 Induction of MKP-1 by transforming growth factor beta (TGF-beta) and IL-10 also contributes to the suppressive effects of these potent anti-inflammatory cytokines on the expression of genes encoding proinflammatory mediators. PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-gamma) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation
p23
p24
cso30:i:ME_GeneExpression
cso30:i:CC_NuclearChromosome
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c60 : 1
stoichiometry:c57 : 1
m2103*0.1
nodelay
--
0
PMID: 18922786,16184516,11842088 Induction of MKP-1 by transforming growth factor beta (TGF-beta) and IL-10 also contributes to the suppressive effects of these potent anti-inflammatory cytokines on the expression of genes encoding proinflammatory mediators. PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-gamma) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation
p25
p25
cso30:i:ME_Phosphorylation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c68 : 1
stoichiometry:c69 : 1
stoichiometry:c70 : 1
m28*m1752*0.1
nodelay
--
0
PMID: 18922786 Interestingly, MKP-1 is phosphorylated by ERK in two distinct regions, which have opposing effects on its stability PMID: 1892786,10617468 Transient activation of ERK phosphorylates MKP-1 at the two extreme C-terminal Ser359 and Ser364, which enhances MKP-1 stabilization without altering its phosphatase activity
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c71 : 1
stoichiometry:c72 : 1
stoichiometry:c73 : 1
m33*m34*0.1
nodelay
--
0
PMID: 18922786,12676937,16286470 This facilitates the interaction of MKP-1 with the Skp-cullin-F-box (SCFSkp2) ubiquitin ligase, which targets MKP-1 for proteasomal degradation
p27
p27
cso30:i:ME_ProteasomeDegradation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c74 : 1
stoichiometry:c77 : 1
stoichiometry:c75 : 1
stoichiometry:c76 : 1
m35*0.1
nodelay
--
0
PMID: 18922786,12676937,16286470 This facilitates the interaction of MKP-1 with the Skp-cullin-F-box (SCFSkp2) ubiquitin ligase, which targets MKP-1 for proteasomal degradation PMID: 18922786 For example, glucocorticoids increase the expression of MKP-1 as well as attenuating proteasomal degradation of MKP-1.
p28
p28
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c78 : 1
stoichiometry:c79 : 1
stoichiometry:c80 : 1
stoichiometry:c81 : 1
m230*m37*m30*0.1
nodelay
--
0
PMID: 18922786 In the presence of the transcription factor nuclear factor-KappaB (NF-KappaB), TNF-alpha induces a rapid and transient activation of JNK.
p29
p29
cso30:i:ME_UnknownActivation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c82 : 1
stoichiometry:c83 : 1
stoichiometry:c84 : 1
stoichiometry:c85 : 1
m230*m38*m30*0.1
nodelay
--
0
PMID: 18922786 Reactive oxygen species (ROS) mediate sustained JNK activation in NF- KappaB?deficient cells by inactivating MKP-1 and several other MKP molecules.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c5 : 1
stoichiometry:c6 : 1
m5*0.1
nodelay
--
0
PMID: 18922786,11902574 HDAC inhibitors induce the expression of a subset of genes involved in cell growth arrest, differentiation, and apoptosis, which accounts for the antitumor effects of these compounds
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c86 : 1
stoichiometry:c87 : 1
stoichiometry:c88 : 1
m38*m1752*0.1
nodelay
--
0
PMID: 18922786 Reactive oxygen species (ROS) mediate sustained JNK activation in NF- KappaB?deficient cells by inactivating MKP-1 and several other MKP molecules. PMID: 18922786 This is achieved by ROS-induced oxidation of the catalytic Cys residue in the MKP molecules, resulting in the loss of phosphatase activity.
p31
p31
cso30:i:CE_Apoptosis_InhibitionOfCellSurvival_
cso30:i:CC_Extracellular
--
--
PMID: 18922786,15766528 Consequently, JNK activation becomes unconstrained, eventually leading to cellular apoptosis (
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c90 : 1
stoichiometry:c91 : 1
1.0*0.1
nodelay
--
0
PMID: 18922786 HDAC inhibitors down-regulated a subset of inflammationassociated genes, including nitric oxide synthase 2 (NOS2), TNFalpha, and IL-6.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c92 : 1
stoichiometry:c93 : 1
1.0*0.1
nodelay
--
0
PMID: 18922786 HDAC inhibitors down-regulated a subset of inflammationassociated genes, including nitric oxide synthase 2 (NOS2), TNFalpha, and IL-6.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c94 : 1
stoichiometry:c95 : 1
1.0*0.1
nodelay
--
0
PMID: 18922786 HDAC inhibitors down-regulated a subset of inflammationassociated genes, including nitric oxide synthase 2 (NOS2), TNFalpha, and IL-6.
p35
p35
cso30:i:ME_Phosphorylation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c99 : 1
stoichiometry:c111 : 1
stoichiometry:c100 : 1
m40*m44*0.1
nodelay
--
0
PMID: 18922786 In particular, HDAC inhibitors decreased phosphorylation of p38 MAPK and its downstream target Elk-1 but not the upstream MAP2Ks MKK3 or MKK6, suggesting that these inhibitors act upon the MAPK pathway at the level of p38, possibly upon a kinase or phosphatase that modifies p38 MAPK.
p36
p36
cso30:i:ME_Binding
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c102 : 1
stoichiometry:c103 : 1
stoichiometry:c104 : 1
stoichiometry:c105 : 1
m1752*m4512*m22*0.1
nodelay
--
0
PMID: 18922786 To identify the acetylated component of the p38 MAPK pathway, Cao et al. immunoprecipitated the histone acetylase p300 and showed that it was associated with MKP-1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c106 : 1
stoichiometry:c107 : 1
stoichiometry:c108 : 1
m42*0.1
nodelay
--
0
PMID: 18922786 Upon stimulation of TLRs, MKP-1 was acetylated at Lys57, and mutation of this residue abrogated the acetylation of MKP-1 by p300 in vitro and in TLR-stimulated cells, suggesting that Lys57 is the crucial residue required for the acetylation of MKP-1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c112 : 1
stoichiometry:c109 : 1
stoichiometry:c113 : 1
m44*m43*0.1
nodelay
--
0
PMID: 18922786 Through a number of biochemical approaches, the authors demonstrated that acetylation of MKP-1 potentiated the interaction between MKP-1 and p38 and, consequently, increased the dephosphorylation of p38 by MKP-1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c98 : 1
stoichiometry:c101 : 1
stoichiometry:c110 : 1
m29*0.1
nodelay
--
0
PMID: 18922786 In particular, HDAC inhibitors decreased phosphorylation of p38 MAPK and its downstream target Elk-1 but not the upstream MAP2Ks MKK3 or MKK6, suggesting that these inhibitors act upon the MAPK pathway at the level of p38, possibly upon a kinase or phosphatase that modifies p38 MAPK.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c8 : 1
1.0*0.1
nodelay
--
0
PMID: 18922786 Paradoxically, HDAC inhibitors also possess potent anti-inflammatory effects by shutting down the expression of genes encoding proinflammatory cytokines and molecules.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c114 : 1
stoichiometry:c115 : 1
m45*0.1
nodelay
--
0
PMID: 18922786 Through a number of biochemical approaches, the authors demonstrated that acetylation of MKP-1 potentiated the interaction between MKP-1 and p38 and, consequently, increased the dephosphorylation of p38 by MKP-1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c9 : 1
stoichiometry:c10 : 1
stoichiometry:c11 : 1
m14*m16*0.1
nodelay
--
0
PMID: 18922786 Activation of MAPK is mediated by a core kinase module consisting of MAPK kinase kinase (MAPKKK, also known as MAP3K), MAPK kinase (MAPKK, also known as MAP2K), and MAPK through sequential protein phosphorylations.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c12 : 1
stoichiometry:c13 : 1
stoichiometry:c14 : 1
m15*m17*0.1
nodelay
--
0
PMID: 18922786 Activation of MAPK is mediated by a core kinase module consisting of MAPK kinase kinase (MAPKKK, also known as MAP3K), MAPK kinase (MAPKK, also known as MAP2K), and MAPK through sequential protein phosphorylations.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c15 : 1
stoichiometry:c16 : 1
stoichiometry:c17 : 1
m18*m219*0.1
nodelay
--
0
PMID: 18922786,11274345,11861597 Activated MAPKs, in turn, phosphorylate activating protein 1 (AP-1) transcription factors and other targets to stimulate gene transcription and immune responses
p8
p8
cso30:i:ME_GeneExpression
cso30:i:CC_Nucleoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c24 : 1
stoichiometry:c61 : 1
stoichiometry:c19 : 1
m22*0.1
nodelay
--
0
PMID: 18922786,16461893,16380513,12444149,15590669,16978838 In macrophages responding to TLR stimulation, there is a strong and rapid induction of MKP-1 mRNA and increase in MKP-1 protein abundance, peaking at 1 hour after stimulation PMID: 18922786,16461893 TLR-induced expression of MKP-1 is reduced in mice lacking either MyD88 or TRIF compared to that in wildtype mice, suggesting that MKP-1 is induced through both MyD88- and TRIF-dependent pathways in response to activation of TLRs PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-gamma) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c20 : 1
stoichiometry:c21 : 1
m21*0.1
nodelay
--
0
PMID: 18922786,16461893,16380513,12444149,15590669,16978838 In macrophages responding to TLR stimulation, there is a strong and rapid induction of MKP-1 mRNA and increase in MKP-1 protein abundance, peaking at 1 hour after stimulation PMID: 18922786,16461893 TLR-induced expression of MKP-1 is reduced in mice lacking either MyD88 or TRIF compared to that in wildtype mice, suggesting that MKP-1 is induced through both MyD88- and TRIF-dependent pathways in response to activation of TLRs
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--