Original Literature | Model OverView |
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Publication
Title
Activation of lymphokine genes in T cells: role of cis-acting DNA elements thatrespond to T cell activation signals.
Affiliation
DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA.
Abstract
Activation of T cells is initiated by the recognition of antigen on antigenpresenting cells to exert the effector functions in immune and inflammatoryresponses. Two types of helper T cell (Th) clones (Th1 and Th2) are defined onthe basis of different patterns of cytokine (lymphokine) secretion. Theydetermine the outcome of an antigenic response toward humoral or cell-mediatedimmunity. Although lymphokine genes are coordinately regulated upon antigenstimulation, they are regulated by the mechanisms common to all as well as thosewhich are unique to each gene. For most lymphokine genes, a combination ofphorbol esters (phorbol 12-myristate 13 acetate, PMA) and calcium ionophores(A23187) is required for their maximal induction. Yet phorbol ester alone orcalcium ionophore alone produce several lymphokines. The production of thegranulocyte-macrophage colony stimulating factor (GM-CSF) is completelydependent on the two signals. We have previously found a cis-acting regionspanning the GM-CSF promoter region (positions -95 to +27) that confersinducibility to reporter genes in transient transfection assays. Furtheranalysis identified three elements required for efficient induction, referred toas GM2, GC-box and conserved lymphokine element (CLE0). GM2 defines a bindingsite for protein(s) whose binding is inducible by PMA. One protein, NF-GM2 issimilar to the transcription factor NF-kB. GC-box is a binding site forconstitutively bound proteins. CLEO defines a binding site for protein(s) whoseoptimum binding is stimulated by PMA and A23187. Viral trans-activators such asTax (human T cell leukemia virus-1, HTLV-1) and E2 (bovine papilloma virus, BPV)proteins are other agents which activate lymphokine gene expression by bypassingT cell receptor (TCR) mediated signaling. The trans-activation domain of E2 andTax is interchangeable although they have no obvious sequence homology betweenthem. The viral trans-activators appear to target specific DNA binding proteinsuch as NF-kB and Sp1 to cis-acting DNA site and promote lymphokine geneexpression without TCR-mediated stimulation.
PMID
1492121
|
Entity
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--
e10
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--
--
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m10
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antigen:TCR:CD3
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e11
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csml-variable:Double
m11
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TCR:CD3
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e12
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MHC
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e13
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m13
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0
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lck
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e14
cso30:c:Protein
cso30:i:CC_Cytosol
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--
csml-variable:Double
m14
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infinite
0
--
lck{p}
--
e15
cso30:c:Protein
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--
csml-variable:Double
m15
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0
--
FYN
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e16
cso30:c:Protein
cso30:i:CC_Cytosol
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--
csml-variable:Double
m16
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infinite
0
--
FYN{p}
--
e17
cso30:c:Protein
cso30:i:CC_Cytosol
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--
csml-variable:Double
m17
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csml-variable:Double
m18
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0
--
csml-variable:Double
m19
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0
--
--
e2
cso30:c:EntityBiologicalCompartment
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csml-variable:Double
m2
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csml-variable:Double
m20
0
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0
--
Ca2+
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e21
cso30:c:SmallMolecule
cso30:i:CC_Cytosol
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csml-variable:Double
m21
0
infinite
0
--
p21ras
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e22
cso30:c:Protein
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csml-variable:Double
m22
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p21ras{active}
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e23
cso30:c:Protein
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m23
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PKC
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e24
cso30:c:Protein
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m24
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PKC{active}
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e25
cso30:c:Protein
cso30:i:CC_Cytosol
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csml-variable:Double
m25
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PMA
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e26
cso30:c:SmallMolecule
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csml-variable:Double
m26
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0
--
A23187
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e27
cso30:c:SmallMolecule
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csml-variable:Double
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IL2
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e28
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m28
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IL2
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e29
cso30:c:Protein
cso30:i:CC_Cytosol
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m29
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e3
cso30:c:EntityBiologicalCompartment
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csml-variable:Double
m3
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--
GMCSF
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e30
cso30:c:mRNA
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csml-variable:Double
m30
0
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GMCSF
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e31
cso30:c:Protein
cso30:i:CC_Cytosol
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csml-variable:Double
m31
0
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IL5
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e32
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
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csml-variable:Double
m32
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IL5
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e33
cso30:c:Protein
cso30:i:CC_Cytosol
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csml-variable:Double
m33
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IL6
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e34
cso30:c:mRNA
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m34
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IL6
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e35
cso30:c:Protein
cso30:i:CC_Cytosol
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m35
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IL10
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e36
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
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m36
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0
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IL10
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e37
cso30:c:Protein
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--
csml-variable:Double
m37
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0
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IL3
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e38
cso30:c:mRNA
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m38
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IL3
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e39
cso30:c:Protein
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csml-variable:Double
m39
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0
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e4
cso30:c:EntityBiologicalCompartment
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0
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IL4
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e40
cso30:c:mRNA
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m40
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0
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IL4
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cso30:c:Protein
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csml-variable:Double
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IFN-gamma
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e42
cso30:c:mRNA
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IFN-gamma
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cso30:c:Protein
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CsA
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e44
cso30:c:SmallMolecule
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m44
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0
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PGE2
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e45
cso30:c:SmallMolecule
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forskolin
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e46
cso30:c:SmallMolecule
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csml-variable:Double
m46
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cholera toxin
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e47
cso30:c:SmallMolecule
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csml-variable:Double
m47
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NF-GM2
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e49
cso30:c:Complex
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e52
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cso30:c:EntityBiologicalCompartment
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e55
cso30:c:EntityBiologicalCompartment
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cso30:c:EntityBiologicalCompartment
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cso30:c:EntityBiologicalCompartment
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e59
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearEnvelope
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--
--
csml-variable:Double
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csml-variable:Double
m6
0
infinite
0
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--
e60
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Chromatin
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--
--
csml-variable:Double
m60
0
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0
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--
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cso30:c:EntityBiologicalCompartment
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--
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--
e62
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearCentromere
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--
--
csml-variable:Double
m62
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m63
0
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0
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IkappaB:NF-kappaB
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e64
cso30:c:Complex
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csml-variable:Double
m64
0
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0
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Nf-kappaB
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e65
cso30:c:Complex
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csml-variable:Double
m65
0
infinite
0
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IkappaB
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e66
cso30:c:Protein
cso30:i:CC_Extracellular
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csml-variable:Double
m66
0
infinite
0
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Nf-kappaB
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e67
cso30:c:Complex
cso30:i:CC_Cytosol
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--
csml-variable:Double
m67
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csml-variable:Double
m68
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infinite
0
--
csml-variable:Double
m69
0
infinite
0
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--
e7
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell
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csml-variable:Double
m7
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csml-variable:Double
m70
0
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0
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TNF-beta:TNFRbeta
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e71
cso30:c:Complex
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csml-variable:Double
m71
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csml-variable:Double
m72
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0
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IL1:IL1R
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e73
cso30:c:Complex
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
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m73
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0
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IL1R
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e74
cso30:c:Protein
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
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csml-variable:Double
m74
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0
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Ets-1
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e75
cso30:c:Protein
cso30:i:CC_Cytosol
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csml-variable:Double
m75
0
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0
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Ets-1{p}
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e76
cso30:c:Protein
cso30:i:CC_Cytosol
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csml-variable:Double
m76
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0
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Ets2
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e77
cso30:c:Protein
cso30:i:CC_Cytosol
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csml-variable:Double
m77
0
infinite
0
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Ets2{p}
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e78
cso30:c:Protein
cso30:i:CC_Cytosol
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csml-variable:Double
m78
0
infinite
0
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--
e8
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell_WithoutCellWall_
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--
--
csml-variable:Double
m8
0
infinite
0
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--
e9
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cytoplasm
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--
--
csml-variable:Double
m9
0
infinite
0
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c2 : 1
stoichiometry:c114 : 1
stoichiometry:c3 : 1
stoichiometry:c1 : 1
m6*m12*0.1
nodelay
--
0
PMID:1492121 The antigen signal received by the T cell receptor (TCR)/CD3 complex is transmitted to the nucleus.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c29 : 1
stoichiometry:c91 : 1
stoichiometry:c28 : 1
m21*0.1
nodelay
--
0
PMID: 1492121 A combination of phorbol ester (PMA) and calcium ionophore (A23187) is required for maximal activation of cytokine genes, suggesting a synergy between the processes mediated by Ca + and by protein kinase C. The production of IL-2 or GM-CSF shows such synergy between these two signals. An immunosuppressive agent, cyclosporin A (CsA), almost completely inhibits production of those cytokines (IL-2, IL-3, IL-4, GM-CSF or IFN-7) whose expression depends on a calcium signal when T cells are activated by PMA/A23187 or antiCD3 antibody.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c31 : 1
stoichiometry:c90 : 1
stoichiometry:c30 : 1
m25*0.1
nodelay
--
0
PMID: 1492121 A combination of phorbol ester (PMA) and calcium ionophore (A23187) is required for maximal activation of cytokine genes, suggesting a synergy between the processes mediated by Ca + and by protein kinase C. The production of IL-2 or GM-CSF shows such synergy between these two signals. An immunosuppressive agent, cyclosporin A (CsA), almost completely inhibits production of those cytokines (IL-2, IL-3, IL-4, GM-CSF or IFN-7) whose expression depends on a calcium signal when T cells are activated by PMA/A23187 or antiCD3 antibody.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c32 : 1
stoichiometry:c35 : 1
stoichiometry:c88 : 1
stoichiometry:c33 : 1
m28*m25*0.1
nodelay
--
0
PMID: 1492121 A combination of phorbol ester (PMA) and calcium ionophore (A23187) is required for maximal activation of cytokine genes, suggesting a synergy between the processes mediated by Ca + and by protein kinase C. The production of IL-2 or GM-CSF shows such synergy between these two signals. An immunosuppressive agent, cyclosporin A (CsA), almost completely inhibits production of those cytokines (IL-2, IL-3, IL-4, GM-CSF or IFN-7) whose expression depends on a calcium signal when T cells are activated by PMA/A23187 or antiCD3 antibody.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c34 : 1
stoichiometry:c37 : 1
stoichiometry:c89 : 1
stoichiometry:c36 : 1
m28*m21*0.1
nodelay
--
0
PMID: 1492121 A combination of phorbol ester (PMA) and calcium ionophore (A23187) is required for maximal activation of cytokine genes, suggesting a synergy between the processes mediated by Ca + and by protein kinase C. The production of IL-2 or GM-CSF shows such synergy between these two signals. An immunosuppressive agent, cyclosporin A (CsA), almost completely inhibits production of those cytokines (IL-2, IL-3, IL-4, GM-CSF or IFN-7) whose expression depends on a calcium signal when T cells are activated by PMA/A23187 or antiCD3 antibody.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c86 : 1
stoichiometry:c38 : 1
m25*0.1
nodelay
--
0
PMID: 1492121 A combination of phorbol ester (PMA) and calcium ionophore (A23187) is required for maximal activation of cytokine genes, suggesting a synergy between the processes mediated by Ca + and by protein kinase C. The production of IL-2 or GM-CSF shows such synergy between these two signals. An immunosuppressive agent, cyclosporin A (CsA), almost completely inhibits production of those cytokines (IL-2, IL-3, IL-4, GM-CSF or IFN-7) whose expression depends on a calcium signal when T cells are activated by PMA/A23187 or antiCD3 antibody.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c40 : 1
stoichiometry:c87 : 1
stoichiometry:c39 : 1
m21*0.1
nodelay
--
0
PMID: 1492121 A combination of phorbol ester (PMA) and calcium ionophore (A23187) is required for maximal activation of cytokine genes, suggesting a synergy between the processes mediated by Ca + and by protein kinase C. The production of IL-2 or GM-CSF shows such synergy between these two signals. An immunosuppressive agent, cyclosporin A (CsA), almost completely inhibits production of those cytokines (IL-2, IL-3, IL-4, GM-CSF or IFN-7) whose expression depends on a calcium signal when T cells are activated by PMA/A23187 or antiCD3 antibody.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c42 : 1
stoichiometry:c46 : 1
stoichiometry:c84 : 1
stoichiometry:c44 : 1
m30*m21*0.1
nodelay
--
0
PMID: 1492121 A combination of phorbol ester (PMA) and calcium ionophore (A23187) is required for maximal activation of cytokine genes, suggesting a synergy between the processes mediated by Ca + and by protein kinase C. The production of IL-2 or GM-CSF shows such synergy between these two signals. An immunosuppressive agent, cyclosporin A (CsA), almost completely inhibits production of those cytokines (IL-2, IL-3, IL-4, GM-CSF or IFN-7) whose expression depends on a calcium signal when T cells are activated by PMA/A23187 or antiCD3 antibody.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c43 : 1
stoichiometry:c47 : 1
stoichiometry:c85 : 1
stoichiometry:c45 : 1
m30*m25*0.1
nodelay
--
0
PMID: 1492121 A combination of phorbol ester (PMA) and calcium ionophore (A23187) is required for maximal activation of cytokine genes, suggesting a synergy between the processes mediated by Ca + and by protein kinase C. The production of IL-2 or GM-CSF shows such synergy between these two signals. An immunosuppressive agent, cyclosporin A (CsA), almost completely inhibits production of those cytokines (IL-2, IL-3, IL-4, GM-CSF or IFN-7) whose expression depends on a calcium signal when T cells are activated by PMA/A23187 or antiCD3 antibody.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c49 : 1
stoichiometry:c48 : 1
m26*0.1
nodelay
--
0
PMID: 1492121 certain cytokines are activated by phorbol esters alone (IL-5, IL-6 and IL-10).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c50 : 1
stoichiometry:c52 : 1
stoichiometry:c51 : 1
m32*m26*0.1
nodelay
--
0
PMID: 1492121 certain cytokines are activated by phorbol esters alone (IL-5, IL-6 and IL-10).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c6 : 1
stoichiometry:c5 : 1
m14*m11*0.1
nodelay
--
0
PMID: 1492121, 1848158 Tyrosine kinases such as lck and fyn have received attention as molecules which may play an important role in coupling the TCR to signal transduction machinery downstream.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c54 : 1
stoichiometry:c53 : 1
m26*0.1
nodelay
--
0
PMID: 1492121 certain cytokines are activated by phorbol esters alone (IL-5, IL-6 and IL-10).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c56 : 1
stoichiometry:c57 : 1
stoichiometry:c55 : 1
m34*m26*0.1
nodelay
--
0
PMID: 1492121 certain cytokines are activated by phorbol esters alone (IL-5, IL-6 and IL-10).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c61 : 1
stoichiometry:c58 : 1
m26*0.1
nodelay
--
0
PMID: 1492121 certain cytokines are activated by phorbol esters alone (IL-5, IL-6 and IL-10).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c59 : 1
stoichiometry:c62 : 1
stoichiometry:c60 : 1
m36*m26*0.1
nodelay
--
0
PMID: 1492121 certain cytokines are activated by phorbol esters alone (IL-5, IL-6 and IL-10).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c67 : 1
stoichiometry:c78 : 1
stoichiometry:c63 : 1
m27*0.1
nodelay
--
0
PMID: 1492121 certain cytokines are activated by phorbol esters alone (IL-5, IL-6 and IL-10 ) or Ca 2 + ionophore alone (IL-3, IL-4 and IFN-gamma). An immunosuppressive agent, cyclosporin A (CsA), almost completely inhibits production of those cytokines (IL-2, IL-3, IL-4, GM-CSF or IFN-7) whose expression depends on a calcium signal when T cells are activated by PMA/A23187 or antiCD3 antibody.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c64 : 1
stoichiometry:c66 : 1
stoichiometry:c79 : 1
stoichiometry:c65 : 1
m38*m27*0.1
nodelay
--
0
PMID: 1492121 certain cytokines are activated by phorbol esters alone (IL-5, IL-6 and IL-10 ) or Ca 2 + ionophore alone (IL-3, IL-4 and IFN-gamma). An immunosuppressive agent, cyclosporin A (CsA), almost completely inhibits production of those cytokines (IL-2, IL-3, IL-4, GM-CSF or IFN-7) whose expression depends on a calcium signal when T cells are activated by PMA/A23187 or antiCD3 antibody.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c71 : 1
stoichiometry:c80 : 1
stoichiometry:c68 : 1
m27*0.1
nodelay
--
0
PMID: 1492121 certain cytokines are activated by phorbol esters alone (IL-5, IL-6 and IL-10 ) or Ca 2 + ionophore alone (IL-3, IL-4 and IFN-gamma). An immunosuppressive agent, cyclosporin A (CsA), almost completely inhibits production of those cytokines (IL-2, IL-3, IL-4, GM-CSF or IFN-7) whose expression depends on a calcium signal when T cells are activated by PMA/A23187 or antiCD3 antibody.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c69 : 1
stoichiometry:c72 : 1
stoichiometry:c81 : 1
stoichiometry:c70 : 1
m40*m27*0.1
nodelay
--
0
PMID: 1492121 certain cytokines are activated by phorbol esters alone (IL-5, IL-6 and IL-10 ) or Ca 2 + ionophore alone (IL-3, IL-4 and IFN-gamma). An immunosuppressive agent, cyclosporin A (CsA), almost completely inhibits production of those cytokines (IL-2, IL-3, IL-4, GM-CSF or IFN-7) whose expression depends on a calcium signal when T cells are activated by PMA/A23187 or antiCD3 antibody.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c77 : 1
stoichiometry:c83 : 1
stoichiometry:c73 : 1
m27*0.1
nodelay
--
0
PMID: 1492121 certain cytokines are activated by phorbol esters alone (IL-5, IL-6 and IL-10 ) or Ca 2 + ionophore alone (IL-3, IL-4 and IFN-gamma). An immunosuppressive agent, cyclosporin A (CsA), almost completely inhibits production of those cytokines (IL-2, IL-3, IL-4, GM-CSF or IFN-7) whose expression depends on a calcium signal when T cells are activated by PMA/A23187 or antiCD3 antibody.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c74 : 1
stoichiometry:c76 : 1
stoichiometry:c82 : 1
stoichiometry:c75 : 1
m42*m27*0.1
nodelay
--
0
PMID: 1492121 certain cytokines are activated by phorbol esters alone (IL-5, IL-6 and IL-10 ) or Ca 2 + ionophore alone (IL-3, IL-4 and IFN-gamma). An immunosuppressive agent, cyclosporin A (CsA), almost completely inhibits production of those cytokines (IL-2, IL-3, IL-4, GM-CSF or IFN-7) whose expression depends on a calcium signal when T cells are activated by PMA/A23187 or antiCD3 antibody.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c9 : 1
stoichiometry:c8 : 1
m16*m11*0.1
nodelay
--
0
PMID: 1492121, 1848158 Tyrosine kinases such as lck and fyn have received attention as molecules which may play an important role in coupling the TCR to signal transduction machinery downstream.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c93 : 1
stoichiometry:c92 : 1
1.0*0.1
nodelay
--
0
PMID: 1492121 PGE2 inhibits the expression of IL-3 and GM-CSF in Thl clone but not in Th2 clone
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c95 : 1
stoichiometry:c94 : 1
1.0*0.1
nodelay
--
0
PMID: 1492121 PGE2 inhibits the expression of IL-3 and GM-CSF in Thl clone but not in Th2 clone
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c97 : 1
stoichiometry:c101 : 1
stoichiometry:c104 : 1
stoichiometry:c96 : 1
1.0*0.1
nodelay
--
0
PMID: 1492121, 1845802, 2162906 PGE2, forskolin and cholera toxin, known to elevate cAMP levels, inhibit IL-2 and IFN-gamma production.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c99 : 1
stoichiometry:c100 : 1
stoichiometry:c102 : 1
stoichiometry:c103 : 1
stoichiometry:c98 : 1
m28*0.1
nodelay
--
0
PMID: 1492121, 1845802, 2162906 PGE2, forskolin and cholera toxin, known to elevate cAMP levels, inhibit IL-2 and IFN-gamma production.
p34
p34
cso30:i:ME_GeneExpression
cso30:i:CC_Nucleoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c108 : 1
stoichiometry:c110 : 1
stoichiometry:c112 : 1
stoichiometry:c105 : 1
1.0*0.1
nodelay
--
0
PMID: 1492121, 1845802, 2162906 PGE2, forskolin and cholera toxin, known to elevate cAMP levels, inhibit IL-2 and IFN-gamma production.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c106 : 1
stoichiometry:c109 : 1
stoichiometry:c111 : 1
stoichiometry:c113 : 1
stoichiometry:c107 : 1
m42*0.1
nodelay
--
0
PMID: 1492121, 1845802, 2162906 PGE2, forskolin and cholera toxin, known to elevate cAMP levels, inhibit IL-2 and IFN-gamma production.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c115 : 1
stoichiometry:c116 : 1
stoichiometry:c117 : 1
m49*m48*0.1
nodelay
--
0
PMID: 1492121 Thus a 10 base pairs sequence from position -91 to -82 of the GM2 motif of the GM-CSF promoter was defined as the binding site for the NF-GM2.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c118 : 1
stoichiometry:c123 : 1
stoichiometry:c119 : 1
stoichiometry:c120 : 1
m64*m26*0.1
nodelay
--
0
PMID: 1492121, 2263644, 1378279 The activation of cytoplasmic NF-kappaB is thought to be mediated by its signal-dependent release from an inhibitory protein designated IkappaB allowing NF-kappaB to translocate to the nucleus and to bind to the kappaB element. NF-kappaB activation is induced by a variety of substances, such as PMA, inflammatory cytokines (TNF-beta and IL-1), agents provoking oxidative stresses (H202).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c121 : 1
stoichiometry:c122 : 1
m65*0.1
nodelay
--
0
PMID: 1492121 The activation of cytoplasmic NF-kappaB is thought to be mediated by its signal-dependent release from an inhibitory protein designated IkappaB allowing NF-kappaB to translocate to the nucleus and to bind to the kappaB element.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c124 : 1
stoichiometry:c127 : 1
stoichiometry:c125 : 1
stoichiometry:c126 : 1
m64*m68*0.1
nodelay
--
0
PMID: 1492121, 2263644, 1378279 NF-kappaB activation is induced by a variety of substances, such as PMA, inflammatory cytokines (TNF-beta and IL-1), agents provoking oxidative stresses (H202).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c13 : 1
stoichiometry:c11 : 1
stoichiometry:c12 : 1
m18*m11*0.1
nodelay
--
0
PMID: 1492121 The major events of early activation involve plasma membrane inositol phospholipid hydrolysis.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c128 : 1
stoichiometry:c134 : 1
stoichiometry:c129 : 1
stoichiometry:c130 : 1
m64*m71*0.1
nodelay
--
0
PMID: 1492121, 2263644, 1378279 NF-kappaB activation is induced by a variety of substances, such as PMA, inflammatory cytokines (TNF-beta and IL-1), agents provoking oxidative stresses (H202).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c131 : 1
stoichiometry:c132 : 1
stoichiometry:c133 : 1
m70*m69*0.1
nodelay
--
0
PMID: 1492121, 2263644, 1378279 NF-kappaB activation is induced by a variety of substances, such as PMA, inflammatory cytokines (TNF-beta and IL-1), agents provoking oxidative stresses (H202).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c135 : 1
stoichiometry:c141 : 1
stoichiometry:c136 : 1
stoichiometry:c137 : 1
m64*m73*0.1
nodelay
--
0
PMID: 1492121, 2263644, 1378279 NF-kappaB activation is induced by a variety of substances, such as PMA, inflammatory cytokines (TNF-beta and IL-1), agents provoking oxidative stresses (H202).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c138 : 1
stoichiometry:c139 : 1
stoichiometry:c140 : 1
m72*m74*0.1
nodelay
--
0
PMID: 1492121, 2263644, 1378279 NF-kappaB activation is induced by a variety of substances, such as PMA, inflammatory cytokines (TNF-beta and IL-1), agents provoking oxidative stresses (H202).
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c142 : 1
stoichiometry:c144 : 1
stoichiometry:c143 : 1
m75*m11*0.1
nodelay
--
0
PMID: 1492121, 2137553 Ets-I and Ets-2 are phosphorylated in T cells upon antigen stimulation and calcium ionophore stimulation mimics this reaction.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c145 : 1
stoichiometry:c147 : 1
stoichiometry:c146 : 1
m77*m11*0.1
nodelay
--
0
PMID: 1492121, 2137553 Ets-I and Ets-2 are phosphorylated in T cells upon antigen stimulation and calcium ionophore stimulation mimics this reaction.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c148 : 1
stoichiometry:c150 : 1
stoichiometry:c149 : 1
m75*m27*0.1
nodelay
--
0
PMID: 1492121, 2137553 Ets-I and Ets-2 are phosphorylated in T cells upon antigen stimulation and calcium ionophore stimulation mimics this reaction.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c151 : 1
stoichiometry:c153 : 1
stoichiometry:c152 : 1
m77*m27*0.1
nodelay
--
0
PMID: 1492121, 2137553 Ets-I and Ets-2 are phosphorylated in T cells upon antigen stimulation and calcium ionophore stimulation mimics this reaction.
p5
p5
cso30:i:ME_ChangeInMaterialConcentration
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c15 : 1
stoichiometry:c16 : 1
stoichiometry:c14 : 1
m11*m19*0.1
nodelay
--
0
PMID: 1492121 The major events of early activation involve (1) plasma membrane inositol phospholipid hydrolysis, (2) increases in cytoplasmic calcium concentration.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c17 : 1
stoichiometry:c19 : 1
stoichiometry:c18 : 1
m22*m11*0.1
nodelay
--
0
PMID: 1492121, 2201921 Activation of p21ras following stimulation of the TCR suggests the involvement of the ras protooncogene in T cell activation.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c20 : 1
stoichiometry:c22 : 1
stoichiometry:c21 : 1
m24*m11*0.1
nodelay
--
0
PMID: 1492121, 2785241 The involvement of one or more isozymes of protein kinase C in TCR-mediated signaling has been established by experiments using phorbol ester or constitutively active protein kinase C.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c24 : 1
stoichiometry:c23 : 1
stoichiometry:c25 : 1
m26*m24*0.1
nodelay
--
0
The involvement of one or more isozymes of protein kinase C in TCR-mediated signaling has been established by experiments using phorbol ester or constitutively active protein kinase C.
p9
p9
cso30:i:ME_ChangeInMaterialConcentration
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c27 : 1
stoichiometry:c26 : 1
m27*0.1
nodelay
--
0
PMID: 1492121 A combination of phorbol ester (PMA) and calcium ionophore (A23187) is required for maximal activation of cytokine genes, suggesting a synergy between the processes mediated by Ca + and by protein kinase C. The production of IL-2 or GM-CSF shows such synergy between these two signals.
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
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:OutputProcess
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:InputInhibitor
threshold
--
0
1,
--
cso30:c:OutputProcess
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: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:InputProcess
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: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:InputProcess
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:OutputProcess
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: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:InputAssociation
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:OutputProcess
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: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: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: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:InputAssociation
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:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
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:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--