Source:http://linkedlifedata.com/resource/pubmed/id/16195372
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2005-9-30
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| pubmed:abstractText |
In normal kidney, TNFR1 is expressed in glomerular and peritubular capillary EC, and some tubular cells, and colocalizes with inactive apoptosis signal-regulating kinase-1 (ASK1) phosphorylated at serine 967. Biopsies of rejecting or ischemic renal allografts, which show both tubular cell injury and proliferation, display down-regulation of TNFR1 and activation of ASK1 as well as up-regulation of TNFR2 on tubular cells, where it colocalizes with phosphorylated endothelial/epithelial tyrosine kinase (Etk). We have exploited receptor-selective muteins and evaluated phosphorylation of receptor-specific kinases to study TNF responses in situ. In organ culture, a TNFR1-specific mutein changes phosphorylation of ASK1 to threonine 845, indicative of kinase activation. A TNFR2-specific mutein down-regulates TNFR1 in glomerular EC, up-regulates TNFR2 and Etk in tubular cells, and induces phosphorylation of Etk. Wild-type TNF induces TNFR2 and Etk and activates both ASK1 and Etk but does not down-regulate TNFR1. Wild-type TNF and TNFR1-specific mutein trigger tubular cell apoptosis whereas wild-type TNF and TNFR2-specific mutein induce tubular cells to express proliferating cell nuclear antigen. Differential activation of ASK1 and Etk by regulated TNFRs in patient-derived materials provides an explanation for diverse and opposing responses to TNF at distinct sites, and an in situ bioassay of TNFR signaling.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/BMX protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinase 5,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Threonine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
|
| pubmed:issn |
1530-6860
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
19
|
| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1637-45
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:16195372-Apoptosis,
pubmed-meshheading:16195372-Biological Assay,
pubmed-meshheading:16195372-Biopsy,
pubmed-meshheading:16195372-Cell Proliferation,
pubmed-meshheading:16195372-Down-Regulation,
pubmed-meshheading:16195372-Enzyme Activation,
pubmed-meshheading:16195372-Humans,
pubmed-meshheading:16195372-In Situ Hybridization,
pubmed-meshheading:16195372-In Situ Nick-End Labeling,
pubmed-meshheading:16195372-Kidney,
pubmed-meshheading:16195372-Kidney Diseases,
pubmed-meshheading:16195372-Kidney Neoplasms,
pubmed-meshheading:16195372-Kidney Transplantation,
pubmed-meshheading:16195372-Kidney Tubules,
pubmed-meshheading:16195372-MAP Kinase Kinase Kinase 5,
pubmed-meshheading:16195372-Microscopy, Confocal,
pubmed-meshheading:16195372-Models, Biological,
pubmed-meshheading:16195372-Organ Culture Techniques,
pubmed-meshheading:16195372-Phosphorylation,
pubmed-meshheading:16195372-Protein-Tyrosine Kinases,
pubmed-meshheading:16195372-Receptors, Tumor Necrosis Factor, Type I,
pubmed-meshheading:16195372-Receptors, Tumor Necrosis Factor, Type II,
pubmed-meshheading:16195372-Signal Transduction,
pubmed-meshheading:16195372-Threonine,
pubmed-meshheading:16195372-Up-Regulation
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| pubmed:year |
2005
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| pubmed:articleTitle |
TNFR1- and TNFR2-mediated signaling pathways in human kidney are cell type-specific and differentially contribute to renal injury.
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| pubmed:affiliation |
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|