|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0031727,
umls-concept:C0037083,
umls-concept:C0205314,
umls-concept:C0258441,
umls-concept:C0332256,
umls-concept:C0336821,
umls-concept:C0439855,
umls-concept:C0679622,
umls-concept:C1336579,
umls-concept:C1366777,
umls-concept:C1523116,
umls-concept:C1710082,
umls-concept:C1823478
|
|
pubmed:issue |
23
|
|
pubmed:dateCreated |
2000-1-31
|
|
pubmed:databankReference |
|
|
pubmed:abstractText |
The activation of NF-kappaB by receptors in the tumor necrosis factor (TNF) receptor and Toll/interleukin-1 (IL-1) receptor families requires the TRAF family of adaptor proteins. Receptor oligomerization causes the recruitment of TRAFs to the receptor complex, followed by the activation of a kinase cascade that results in the phosphorylation of IkappaB. TANK is a TRAF-binding protein that can inhibit the binding of TRAFs to receptor tails and can also inhibit NF-kappaB activation by these receptors. However, TANK also displays the ability to stimulate TRAF-mediated NF-kappaB activation. In this report, we investigate the mechanism of the stimulatory activity of TANK. We find that TANK interacts with TBK1 (TANK-binding kinase 1), a novel IKK-related kinase that can activate NF-kappaB in a kinase-dependent manner. TBK1, TANK and TRAF2 can form a ternary complex, and complex formation appears to be required for TBK1 activity. Kinase-inactive TBK1 inhibits TANK-mediated NF-kappaB activation but does not block the activation mediated by TNF-alpha, IL-1 or CD40. The TBK1-TANK-TRAF2 signaling complex functions upstream of NIK and the IKK complex and represents an alternative to the receptor signaling complex for TRAF-mediated activation of NF-kappaB.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD40,
http://linkedlifedata.com/resource/pubmed/chemical/CD40 Ligand,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TANK protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TNF Receptor-Associated Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Dec
|
|
pubmed:issn |
0261-4189
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
1
|
|
pubmed:volume |
18
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
6694-704
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:10581243-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:10581243-Amino Acid Sequence,
pubmed-meshheading:10581243-Antigens, CD40,
pubmed-meshheading:10581243-CD40 Ligand,
pubmed-meshheading:10581243-Cell Line,
pubmed-meshheading:10581243-Dose-Response Relationship, Drug,
pubmed-meshheading:10581243-Enzyme Activation,
pubmed-meshheading:10581243-Humans,
pubmed-meshheading:10581243-Interleukin-1,
pubmed-meshheading:10581243-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:10581243-Membrane Glycoproteins,
pubmed-meshheading:10581243-Mitogen-Activated Protein Kinases,
pubmed-meshheading:10581243-Molecular Sequence Data,
pubmed-meshheading:10581243-NF-kappa B,
pubmed-meshheading:10581243-Protein-Serine-Threonine Kinases,
pubmed-meshheading:10581243-Proteins,
pubmed-meshheading:10581243-Sequence Homology, Amino Acid,
pubmed-meshheading:10581243-Signal Transduction,
pubmed-meshheading:10581243-TNF Receptor-Associated Factor 2,
pubmed-meshheading:10581243-Tumor Necrosis Factor-alpha,
pubmed-meshheading:10581243-Two-Hybrid System Techniques
|
|
pubmed:year |
1999
|
|
pubmed:articleTitle |
NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase.
|
|
pubmed:affiliation |
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
