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We also showed that
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No direct association was observed between TICAM-1 and the
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</csml:processSimulationProperty>
<csml:viewProperty>
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<csml:comments>
<csml:comment type="text">PMID: 15618008,14519765
TICAM-2 (or TRAM) was cloned as a TLR4-
binding protein in yeast

PMID: 15618008
TLR4
directly recruits TICAM-2, but not TICAM-1

PMID: 15618008,14519765
Physical association of
HA-tagged TICAM-2 with Flag-Tagged TLR4 tested
by immunoprecipitation and Western blotting confirmed
direct binding of TICAM-2 to TLR4 in HEK293
cells</csml:comment>
</csml:comments>
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</csml:connector>
<csml:connector id="c14" name="c14" refID="e11" type="cso30:c:OutputProcess">
<csml:connectorSimulationProperty>
<csml:connectorFiring connectorFiringStyle="csml-connectorFiringStyle:threshold" value="0"/>
<csml:connectorKinetic>
<csml:parameter key="stoichiometry" value="1"/>
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</csml:connectorSimulationProperty>
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</csml:processSimulationProperty>
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<csml:comments>
<csml:comment type="text">PMID: 15618008
When over-expressed in
HEK cells, TICAM-2 formed dimers</csml:comment>
</csml:comments>
</csml:process>
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<csml:connectorSimulationProperty>
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</csml:processKinetic>
</csml:processSimulationProperty>
<csml:viewProperty>
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<csml:comment type="text">PMID: 15618008
TLR4 recruited
TICAM-2 in the absence of TICAM-1, but TLR4 recruited
TICAM-1 only in the presence of TICAM-2

PMID: 15618008
TICAM-2 appears to
bridge TLR4 and TICAM-1 by forming heterodimers
with TICAM-1.
</csml:comment>
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<csml:comments>
<csml:comment type="text">indirect</csml:comment>
</csml:comments>
</csml:connector>
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<csml:connectorSimulationProperty>
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</csml:connectorSimulationProperty>
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<csml:processSimulationProperty>
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</csml:processKinetic>
</csml:processSimulationProperty>
<csml:viewProperty>
<csml:position position="auto" positionID="default" x="308.0" y="312.0"/>
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<csml:comments>
<csml:comment type="text">PMID: 15618008,12539043,12471095
Interferon-regulatory factor
(IRF)-3 dimerizes as a result of TICAM-1 transfection suggesting TICAM-1 is the molecule that activates
IRF-3, which in turn enhances activation of the IFN
promoter

PMID: 15618008,15611223
TICAM-1 recruits a kinase
complex consisting of NAP1, IKKepsilon, and TBK1
to induce IRF-3 activation</csml:comment>
</csml:comments>
</csml:process>
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</csml:connector>
<csml:connector id="c23" name="c23" refID="e13" type="cso30:c:OutputProcess">
<csml:connectorSimulationProperty>
<csml:connectorFiring connectorFiringStyle="csml-connectorFiringStyle:threshold" value="0"/>
<csml:connectorKinetic>
<csml:parameter key="stoichiometry" value="1"/>
</csml:connectorKinetic>
</csml:connectorSimulationProperty>
<csml:viewProperty>
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</csml:processKinetic>
</csml:processSimulationProperty>
<csml:viewProperty>
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<csml:biologicalProperty refBiologicalEventID="cso30:i:ME_Dimerization" refCellComponentID="cso30:i:CC_Cytosol"/>
<csml:comments>
<csml:comment type="text">PMID: 15618008,12539043,12471095
Interferon-regulatory factor
(IRF)-3 dimerizes as a result of TICAM-1 transfection suggesting TICAM-1 is the molecule that activates
IRF-3, which in turn enhances activation of the IFN
promoter</csml:comment>
</csml:comments>
</csml:process>
<csml:process id="p9" name="p9" type="cso30:c:ProcessBiological">
<csml:connector id="c24" name="c24" refID="e5" type="cso30:c:InputProcess">
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Moderate activation of NF-KappaB was
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Moderate activation of NF-KappaB was
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Moderate activation of NF-KappaB was
induced by MyD88 or Mal/TIRAP and TICAM-1</csml:comment>
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<csml:comment type="text">PMID: 15618008
Moderate activation of NF-KappaB was
induced by MyD88 or Mal/TIRAP and TICAM-1

PMID: 15618008,15064760
TICAM-1 recruits RIP1 in
its C-terminal domain and induces NF-kappaB activation</csml:comment>
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<csml:comments>
<csml:comment type="text">PMID: 15618008
Robust activation of
the IFN-beta promoter was observed when cells were
transfected with TICAM-1

PMID: 15618008
Interferon-regulatory factor
(IRF)-3 dimerizes as a result of TICAM-1 transfection suggesting TICAM-1 is the molecule that activates
IRF-3, which in turn enhances activation of the IFN
promoter</csml:comment>
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<csml:comment type="text">PMID: 15618008
TICAM-2 appears to
bridge TLR4 and TICAM-1 by forming heterodimers
with TICAM-1.

PMID: 15618008
TLR4 recruited
TICAM-2 in the absence of TICAM-1, but TLR4 recruited
TICAM-1 only in the presence of TICAM-2.</csml:comment>
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<csml:comment type="text">PMID: 15618008,15064760
TICAM-1 recruits RIP1 in
its C-terminal domain and induces NF-kappaB activation</csml:comment>
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<csml:comment type="text">PMID: 15618008,15064760
TICAM-1 recruits RIP1 in
its C-terminal domain and induces NF-KappaB activation</csml:comment>
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</csml:connector>
<csml:connector id="c46" name="c46" refID="e18" type="cso30:c:OutputProcess">
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<csml:connectorKinetic>
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</csml:connectorSimulationProperty>
<csml:viewProperty>
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<csml:processKinetic calcStyle="csml-calcStyle:speed" fast="false" kineticStyle="csml-kineticStyle:mass">
<csml:parameter key="coefficient2" value="1.0"/>
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</csml:processKinetic>
</csml:processSimulationProperty>
<csml:viewProperty>
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<csml:comments>
<csml:comment type="text">PMID: 15618008,15064760
TICAM-1 recruits RIP1 in
its C-terminal domain and induces NF-kappaB activation</csml:comment>
</csml:comments>
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</csml:connector>
<csml:connector id="c49" name="c49" refID="e20" type="cso30:c:OutputProcess">
<csml:connectorSimulationProperty>
<csml:connectorFiring connectorFiringStyle="csml-connectorFiringStyle:threshold" value="0"/>
<csml:connectorKinetic>
<csml:parameter key="stoichiometry" value="1"/>
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</csml:connectorSimulationProperty>
<csml:viewProperty>
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</csml:connector>
<csml:processSimulationProperty>
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<csml:processKinetic calcStyle="csml-calcStyle:speed" fast="false" kineticStyle="csml-kineticStyle:mass">
<csml:parameter key="coefficient2" value="1.0"/>
<csml:parameter key="coefficient1" value="0.1"/>
</csml:processKinetic>
</csml:processSimulationProperty>
<csml:viewProperty>
<csml:position position="auto" positionID="default" x="377.0" y="213.0"/>
<csml:shape shapeID="default" visible="true">
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<csml:biologicalProperty refBiologicalEventID="cso30:i:ME_Binding" refCellComponentID="cso30:i:CC_Cytoplasm"/>
<csml:comments>
<csml:comment type="text">PMID: 15618008,15611223
TICAM-1 recruits a kinase
complex consisting of NAP1, IKKepsilon, and TBK1
to induce IRF-3 activation</csml:comment>
</csml:comments>
</csml:process>
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<csml:comment type="text">indirect</csml:comment>
</csml:comments>
</csml:connector>
<csml:connector id="c52" name="c52" refID="MO000007694" type="cso30:c:InputProcess">
<csml:connectorSimulationProperty>
<csml:connectorFiring connectorFiringStyle="csml-connectorFiringStyle:threshold" value="0"/>
<csml:connectorKinetic>
<csml:parameter key="stoichiometry" value="1"/>
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<csml:viewProperty>
<csml:position position="auto" positionID="default" x="429.0" y="481.0"/>
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</csml:connector>
<csml:connector id="c53" name="c53" refID="e21" type="cso30:c:OutputProcess">
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<csml:processKinetic calcStyle="csml-calcStyle:speed" fast="false" kineticStyle="csml-kineticStyle:mass">
<csml:parameter key="coefficient2" value="1.0"/>
<csml:parameter key="coefficient1" value="0.1"/>
</csml:processKinetic>
</csml:processSimulationProperty>
<csml:viewProperty>
<csml:position position="auto" positionID="default" x="451.0" y="519.0"/>
<csml:shape shapeID="default" visible="true">
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<csml:biologicalProperty refBiologicalEventID="cso30:i:ME_Phosphorylation" refCellComponentID="cso30:i:CC_Cytoplasm"/>
<csml:comments>
<csml:comment type="text">PMID: 15618008
IRF-3 phosphorylation induced by TICAM-1 transfection
was also promoted in the presence of TICAM-
2.</csml:comment>
</csml:comments>
</csml:process>
<csml:process id="p20" name="p20" type="cso30:c:ProcessBiological">
<csml:connector id="c54" name="c54" refID="MO000022528" type="cso30:c:InputProcess">
<csml:connectorSimulationProperty>
<csml:connectorFiring connectorFiringStyle="csml-connectorFiringStyle:threshold" value="0"/>
<csml:connectorKinetic>
<csml:parameter key="stoichiometry" value="1"/>
</csml:connectorKinetic>
</csml:connectorSimulationProperty>
<csml:viewProperty>
<csml:position position="auto" positionID="default" x="867.0" y="869.0"/>
<csml:shape shapeID="default" visible="true">
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<figure xmlns="http://www.csml.org/csml/cigraphics">
<processConnector depth="0" points="867.0 869.0 921.3863310579156 886.543977760618" visible="true"/>
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<targetArrow xmlns="http://www.csml.org/csml/cigraphics">
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</csml:connector>
<csml:connector id="c55" name="c55" refID="e14" type="cso30:c:InputProcess">
<csml:connectorSimulationProperty>
<csml:connectorFiring connectorFiringStyle="csml-connectorFiringStyle:threshold" value="0"/>
<csml:connectorKinetic>
<csml:parameter key="stoichiometry" value="1"/>
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<csml:viewProperty>
<csml:position position="auto" positionID="default" x="955.2900319205088" y="746.0"/>
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</csml:toolSpecificGraphics>
</csml:shape>
</csml:viewProperty>
</csml:connector>
<csml:connector id="c56" name="c56" refID="e22" type="cso30:c:OutputProcess">
<csml:connectorSimulationProperty>
<csml:connectorFiring connectorFiringStyle="csml-connectorFiringStyle:threshold" value="0"/>
<csml:connectorKinetic>
<csml:parameter key="stoichiometry" value="1"/>
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</csml:connectorSimulationProperty>
<csml:viewProperty>
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</csml:connector>
<csml:processSimulationProperty>
<csml:priority value="0"/>
<csml:firing firingOnce="false" firingStyle="csml-firingStyle:and" type="csml-variable:Boolean" value="true"/>
<csml:delay delayStyle="nodelay" value="0.0"/>
<csml:processKinetic calcStyle="csml-calcStyle:speed" fast="false" kineticStyle="csml-kineticStyle:mass">
<csml:parameter key="coefficient2" value="1.0"/>
<csml:parameter key="coefficient1" value="0.1"/>
</csml:processKinetic>
</csml:processSimulationProperty>
<csml:viewProperty>
<csml:position position="auto" positionID="default" x="929.0" y="881.0"/>
<csml:shape shapeID="default" visible="true">
<csml:image fileFormat="svg" filePath="" fileType="resourceFile" height="22.0" outlineColor="0 0 0 0" resourceID="10005" width="22.0"/>
<csml:toolSpecificGraphics/>
</csml:shape>
</csml:viewProperty>
<csml:biologicalProperty refBiologicalEventID="cso30:i:ME_Binding" refCellComponentID="cso30:i:CC_Cytoplasm"/>
<csml:comments>
<csml:comment type="text">PMID: 15618008
Moderate activation of NF-KappaB was
induced by MyD88 or Mal/TIRAP and TICAM-1
</csml:comment>
</csml:comments>
</csml:process>
<csml:process id="p21" name="p21" type="cso30:c:ProcessBiological">
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<csml:comments>
<csml:comment type="text">indirect</csml:comment>
</csml:comments>
</csml:connector>
<csml:connector id="c59" name="c59" refID="G010329" type="cso30:c:OutputProcess">
<csml:connectorSimulationProperty>
<csml:connectorFiring connectorFiringStyle="csml-connectorFiringStyle:threshold" value="0"/>
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</csml:processKinetic>
</csml:processSimulationProperty>
<csml:viewProperty>
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<csml:comments>
<csml:comment type="text">PMID: 15618008
These two adapters mediate the
NF-KappaB activation and IRF-3 activation respectively resulting
in the reported cytokine induction (TNF-alpha, IL-6 and IL-12p40).</csml:comment>
</csml:comments>
</csml:process>
<csml:process id="p22" name="p21" type="cso30:c:ProcessBiological">
<csml:connector id="c60" name="c60" refID="e15" type="cso30:c:InputAssociation">
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<csml:comments>
<csml:comment type="text">indirect</csml:comment>
</csml:comments>
</csml:connector>
<csml:connector id="c62" name="c62" refID="G010657" type="cso30:c:OutputProcess">
<csml:connectorSimulationProperty>
<csml:connectorFiring connectorFiringStyle="csml-connectorFiringStyle:threshold" value="0"/>
<csml:connectorKinetic>
<csml:parameter key="stoichiometry" value="1"/>
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</csml:connectorSimulationProperty>
<csml:viewProperty>
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<csml:processKinetic calcStyle="csml-calcStyle:speed" fast="false" kineticStyle="csml-kineticStyle:mass">
<csml:parameter key="coefficient2" value="1.0"/>
<csml:parameter key="coefficient1" value="0.1"/>
</csml:processKinetic>
</csml:processSimulationProperty>
<csml:viewProperty>
<csml:position position="auto" positionID="default" x="623.0" y="871.0"/>
<csml:shape shapeID="default" visible="true">
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<csml:toolSpecificGraphics/>
</csml:shape>
</csml:viewProperty>
<csml:biologicalProperty refBiologicalEventID="cso30:i:ME_GeneExpression" refCellComponentID="cso30:i:CC_Nucleoplasm"/>
<csml:comments>
<csml:comment type="text">PMID: 15618008
These two adapters mediate the
NF-KappaB activation and IRF-3 activation respectively resulting
in the reported cytokine induction (TNF-alpha, IL-6 and IL-12p40).</csml:comment>
</csml:comments>
</csml:process>
<csml:process id="p23" name="p21" type="cso30:c:ProcessBiological">
<csml:connector id="c61" name="c61" refID="e15" type="cso30:c:InputAssociation">
<csml:connectorSimulationProperty>
<csml:connectorFiring connectorFiringStyle="csml-connectorFiringStyle:threshold" value="0"/>
<csml:connectorKinetic>
<csml:parameter key="stoichiometry" value="1"/>
</csml:connectorKinetic>
</csml:connectorSimulationProperty>
<csml:viewProperty>
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<figure xmlns="http://www.csml.org/csml/cigraphics">
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</csml:viewProperty>
<csml:comments>
<csml:comment type="text">indirect</csml:comment>
</csml:comments>
</csml:connector>
<csml:connector id="c63" name="c63" refID="G010262" type="cso30:c:OutputProcess">
<csml:connectorSimulationProperty>
<csml:connectorFiring connectorFiringStyle="csml-connectorFiringStyle:threshold" value="0"/>
<csml:connectorKinetic>
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</csml:connectorSimulationProperty>
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</csml:processKinetic>
</csml:processSimulationProperty>
<csml:viewProperty>
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<csml:shape shapeID="default" visible="true">
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<csml:biologicalProperty refBiologicalEventID="cso30:i:ME_GeneExpression" refCellComponentID="cso30:i:CC_Nucleoplasm"/>
<csml:comments>
<csml:comment type="text">PMID: 15618008
These two adapters mediate the
NF-KappaB activation and IRF-3 activation respectively resulting
in the reported cytokine induction (TNF-alpha, IL-6 and IL-12p40).</csml:comment>
</csml:comments>
</csml:process>
<csml:process id="p24" name="p18" type="cso30:c:ProcessBiological">
<csml:connector id="c64" name="c64" refID="e19" type="cso30:c:InputProcess">
<csml:connectorSimulationProperty>
<csml:connectorFiring connectorFiringStyle="csml-connectorFiringStyle:threshold" value="0"/>
<csml:connectorKinetic>
<csml:parameter key="stoichiometry" value="1"/>
</csml:connectorKinetic>
</csml:connectorSimulationProperty>
<csml:viewProperty>
<csml:position position="auto" positionID="default" x="538.0" y="323.0"/>
<csml:shape shapeID="default" visible="true">
<csml:toolSpecificGraphics>
<figure xmlns="http://www.csml.org/csml/cigraphics">
<processConnector depth="0" points="538.0 323.0 605.76 555.32" visible="true"/>
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<targetArrow xmlns="http://www.csml.org/csml/cigraphics">
<processConnectorArrow points="0.0 0.0 0.0 6.0 8.0 3.0" pointsInAbsoluteCoordinate="608.64 554.48 602.88 556.16 608.0 563.0" size="8.0 6.0"/>
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</csml:toolSpecificGraphics>
</csml:shape>
</csml:viewProperty>
</csml:connector>
<csml:connector id="c65" name="c65" refID="e12" type="cso30:c:InputProcess">
<csml:connectorSimulationProperty>
<csml:connectorFiring connectorFiringStyle="csml-connectorFiringStyle:threshold" value="0"/>
<csml:connectorKinetic>
<csml:parameter key="stoichiometry" value="1"/>
</csml:connectorKinetic>
</csml:connectorSimulationProperty>
<csml:viewProperty>
<csml:position position="auto" positionID="default" x="631.9971570716941" y="564.0"/>
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</csml:viewProperty>
</csml:connector>
<csml:connector id="c66" name="c66" refID="e23" type="cso30:c:OutputProcess">
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TICAM-1 recruits a kinase
complex consisting of NAP1, IKKepsilon, and TBK1
to induce IRF-3 activation</csml:comment>
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Interferon-regulatory factor
(IRF)-3 dimerizes as a result of TICAM-1 transfection suggesting TICAM-1 is the molecule that activates
IRF-3, which in turn enhances activation of the IFN
promoter

PMID: 15618008,15611223
TICAM-1 recruits a kinase
complex consisting of NAP1, IKKepsilon, and TBK1
to induce IRF-3 activation</csml:comment>
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<csml:comments>
<csml:comment type="text">PMID: 15618008
The maturation
markers of DCs, CD80, CD83 and CD86, are upregulated
by TLR signaling.</csml:comment>
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TRAF6
was reported to bind the N-terminus of TICAM-1, but the macrophages from TRAF6
gene-disrupted mice expressed no phenotype related
to TICAM-1 activation </csml:comment>
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</csml:process>
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TRAF6
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gene-disrupted mice expressed no phenotype related
to TICAM-1 activation </csml:comment>
</csml:comments>
</csml:process>
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The maturation
markers of DCs, CD80, CD83 and CD86, are upregulated
by TLR signaling.</csml:comment>
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The maturation
markers of DCs, CD80, CD83 and CD86, are upregulated
by TLR signaling.</csml:comment>
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The maturation
markers of DCs, CD80, CD83 and CD86, are upregulated
by TLR signaling.</csml:comment>
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The maturation
markers of DCs, CD80, CD83 and CD86, are upregulated
by TLR signaling.</csml:comment>
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The maturation
markers of DCs, CD80, CD83 and CD86, are upregulated
by TLR signaling.</csml:comment>
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The maturation
markers of DCs, CD80, CD83 and CD86, are upregulated
by TLR signaling.</csml:comment>
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<csml:comment type="text">PMID: 15618008
The maturation
markers of DCs, CD80, CD83 and CD86, are upregulated
by TLR signaling.</csml:comment>
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The maturation
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by TLR signaling.</csml:comment>
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