|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
7
|
|
pubmed:dateCreated |
2009-6-22
|
|
pubmed:abstractText |
Transforming growth factor-alpha-activated kinase 1 (TAK1) has been widely recognized as a kinase that regulates multiple intracellular signaling pathways evoked by cytokines and immune receptor activation. We have recently reported that tumor necrosis factor-alpha (TNF-alpha) triggers internalization of epidermal growth factor receptor (EGFR) through a TAK1-p38alpha signaling pathway, which results in a transient suppression of the EGFR. In the present study, we investigated the pathway of intracellular signaling in the opposite direction. Ligand-induced activation of EGFR caused phosphorylation of the TAK1-binding proteins TAB1 and TAB2 in a TAK1-independent manner. EGFR-mediated phosphorylation of TAB1 was completely inhibited by a chemical inhibitor and siRNA of p38alpha. The phosphorylation of TAB1 was occurred at Ser-423 and Thr-431, the residues underlying the p38-mediated feedback inhibition of TAK1. In contrast, phosphorylation of TAB2 was sustained, and largely resistant to p38 inhibition. The inducible phosphorylation of TAB1 interfered with a response of EGF-treated cells to TNF-alpha-induced TAK1 activation, which led to the reduction of NF-kappaB activation. Collectively, these results demonstrated that EGFR activation interfered with TNF-alpha-induced TAK1 activation via p38-mediated phosphorylation of TAB1.
|
|
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/EGFR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/MAP kinase kinase kinase 7,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Monoester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/TAB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jul
|
|
pubmed:issn |
0006-3002
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
1793
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1156-64
|
|
pubmed:dateRevised |
2011-11-2
|
|
pubmed:meshHeading |
pubmed-meshheading:19393267-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:19393267-Blotting, Western,
pubmed-meshheading:19393267-Cells, Cultured,
pubmed-meshheading:19393267-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:19393267-Epidermal Growth Factor,
pubmed-meshheading:19393267-Humans,
pubmed-meshheading:19393267-Immunoblotting,
pubmed-meshheading:19393267-Immunoprecipitation,
pubmed-meshheading:19393267-Kidney,
pubmed-meshheading:19393267-Luciferases,
pubmed-meshheading:19393267-MAP Kinase Kinase Kinases,
pubmed-meshheading:19393267-NF-kappa B,
pubmed-meshheading:19393267-Phosphoric Monoester Hydrolases,
pubmed-meshheading:19393267-Phosphorylation,
pubmed-meshheading:19393267-RNA, Messenger,
pubmed-meshheading:19393267-RNA, Small Interfering,
pubmed-meshheading:19393267-Receptor, Epidermal Growth Factor,
pubmed-meshheading:19393267-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19393267-Signal Transduction,
pubmed-meshheading:19393267-Tumor Necrosis Factor-alpha,
pubmed-meshheading:19393267-p38 Mitogen-Activated Protein Kinases
|
|
pubmed:year |
2009
|
|
pubmed:articleTitle |
Cross interference with TNF-alpha-induced TAK1 activation via EGFR-mediated p38 phosphorylation of TAK1-binding protein 1.
|
|
pubmed:affiliation |
Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
