Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-9-10
pubmed:abstractText
The molecular regulation of the recruitment of initial signaling complexes at the TNF-R1 is poorly defined. We demonstrate here that within minutes internalized TNF-R1 (TNF receptosomes) recruits TRADD, FADD, and caspase-8 to establish the "death-inducing signaling complex" (DISC). In addition, we identified the TNF-R1 internalization domain (TRID) required for receptor endocytosis and provide evidence that TNF-R1 internalization, DISC formation, and apoptosis are inseparable events. Analyzing cell lines expressing an internalization-deficient receptor (TNF-R1 DeltaTRID) revealed that recruitment of RIP-1 and TRAF-2 to TNF-R1 occurred at the level of the plasma membrane. In contrast, aggregation of TRADD, FADD, and caspase-8 to establish the TNF-R1-associated DISC is critically dependent on receptor endocytosis. Furthermore, fusion of TNF receptosomes with trans-Golgi vesicles results in activation of acid sphingomyelinase and cathepsin D. Thus, TNF receptosomes establish the different TNF signaling pathways by compartmentalization of plasma membrane-derived endocytic vesicles harboring the TNF-R1-associated DISC.
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, CD, http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Casp8 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8, http://linkedlifedata.com/resource/pubmed/chemical/Caspases, http://linkedlifedata.com/resource/pubmed/chemical/Death Domain Receptor Signaling..., http://linkedlifedata.com/resource/pubmed/chemical/FADD protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Fadd protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Fas-Associated Death Domain Protein, http://linkedlifedata.com/resource/pubmed/chemical/GPI-Linked Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proteins, 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/TNF Receptor-Associated Death..., http://linkedlifedata.com/resource/pubmed/chemical/TNF Receptor-Associated Factor 1, http://linkedlifedata.com/resource/pubmed/chemical/TNFRSF10C protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Tradd protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor Decoy..., http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor...
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1074-7613
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
415-28
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15357952-Adaptor Proteins, Signal Transducing, pubmed-meshheading:15357952-Animals, pubmed-meshheading:15357952-Antigens, CD, pubmed-meshheading:15357952-Apoptosis, pubmed-meshheading:15357952-Carrier Proteins, pubmed-meshheading:15357952-Caspase 8, pubmed-meshheading:15357952-Caspases, pubmed-meshheading:15357952-Cell Membrane, pubmed-meshheading:15357952-Death Domain Receptor Signaling Adaptor Proteins, pubmed-meshheading:15357952-Endocytosis, pubmed-meshheading:15357952-Endosomes, pubmed-meshheading:15357952-Fas-Associated Death Domain Protein, pubmed-meshheading:15357952-Fluorescent Antibody Technique, pubmed-meshheading:15357952-GPI-Linked Proteins, pubmed-meshheading:15357952-Golgi Apparatus, pubmed-meshheading:15357952-HeLa Cells, pubmed-meshheading:15357952-Humans, pubmed-meshheading:15357952-Mice, pubmed-meshheading:15357952-Microscopy, Electron, pubmed-meshheading:15357952-NIH 3T3 Cells, pubmed-meshheading:15357952-Precipitin Tests, pubmed-meshheading:15357952-Proteins, pubmed-meshheading:15357952-Receptors, Tumor Necrosis Factor, pubmed-meshheading:15357952-Receptors, Tumor Necrosis Factor, Type I, pubmed-meshheading:15357952-Signal Transduction, pubmed-meshheading:15357952-TNF Receptor-Associated Death Domain Protein, pubmed-meshheading:15357952-TNF Receptor-Associated Factor 1, pubmed-meshheading:15357952-Tumor Necrosis Factor Decoy Receptors, pubmed-meshheading:15357952-Tumor Necrosis Factor Receptor-Associated Peptides and..., pubmed-meshheading:15357952-U937 Cells
pubmed:year
2004
pubmed:articleTitle
Compartmentalization of TNF receptor 1 signaling: internalized TNF receptosomes as death signaling vesicles.
pubmed:affiliation
Institute of Medical Microbiology and Hygiene, University of Regensburg, D-93053, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't