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rdf:type |
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lifeskim:mentions |
umls-concept:C0033684,
umls-concept:C0037903,
umls-concept:C0077503,
umls-concept:C0086982,
umls-concept:C0205314,
umls-concept:C0332281,
umls-concept:C0449432,
umls-concept:C0597357,
umls-concept:C0679622,
umls-concept:C1179435,
umls-concept:C1419030,
umls-concept:C1420280,
umls-concept:C1521761,
umls-concept:C1524073,
umls-concept:C1548799,
umls-concept:C1704675,
umls-concept:C1705248,
umls-concept:C1879547,
umls-concept:C1882074,
umls-concept:C2825492
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pubmed:issue |
9
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pubmed:dateCreated |
2002-10-22
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pubmed:abstractText |
Factor associated with neutral sphingomyelinase activation (FAN) represents a p55 TNFR (TNF-R55)-associated protein essential for the activation of neutral sphingomyelinase. By means of the yeast interaction trap system, we have identified the scaffolding protein receptor for activated C-kinase (RACK)1 as an interaction partner of FAN. Mapping studies in yeast revealed that RACK1 is recruited to the C-terminal WD-repeat region of FAN and binds to FAN through a domain located within WD repeats V to VII of RACK1. Our data indicate that binding of both proteins is not mediated by linear motifs but requires folding into a secondary structure, such as the multibladed propeller characteristic of WD-repeat proteins. The interaction of FAN and RACK1 was verified in vitro by glutathione S-transferase-based coprecipitation assays as well as in eukaryotic cells by coimmunoprecipitation experiments. Colocalization studies in transfected cells suggest that TNF-R55 forms a complex with FAN and that this complex recruits RACK1 to the plasma membrane. Furthermore, activation of N-SMase by TNF was strongly enhanced when RACK1, FAN, and a noncytotoxic TNF-R55 mutant were expressed concurrently, suggesting RACK1 as a modulator of N-SMase activation. Together, these findings implicate RACK1 as a novel component of the signaling pathways of TNF-R55.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/NSMAF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
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/Sphingomyelin Phosphodiesterase,
http://linkedlifedata.com/resource/pubmed/chemical/receptors for activated C kinase
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
169
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5161-70
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:12391233-Amino Acid Motifs,
pubmed-meshheading:12391233-Amino Acid Sequence,
pubmed-meshheading:12391233-Animals,
pubmed-meshheading:12391233-Antigens, CD,
pubmed-meshheading:12391233-COS Cells,
pubmed-meshheading:12391233-Cell Line,
pubmed-meshheading:12391233-Enzyme Activation,
pubmed-meshheading:12391233-HeLa Cells,
pubmed-meshheading:12391233-Humans,
pubmed-meshheading:12391233-Intracellular Fluid,
pubmed-meshheading:12391233-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:12391233-Jurkat Cells,
pubmed-meshheading:12391233-Molecular Sequence Data,
pubmed-meshheading:12391233-Peptide Fragments,
pubmed-meshheading:12391233-Precipitin Tests,
pubmed-meshheading:12391233-Protein Binding,
pubmed-meshheading:12391233-Protein Interaction Mapping,
pubmed-meshheading:12391233-Protein Kinase C,
pubmed-meshheading:12391233-Proteins,
pubmed-meshheading:12391233-Receptors, Cell Surface,
pubmed-meshheading:12391233-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:12391233-Receptors, Tumor Necrosis Factor, Type I,
pubmed-meshheading:12391233-Repetitive Sequences, Amino Acid,
pubmed-meshheading:12391233-Signal Transduction,
pubmed-meshheading:12391233-Sphingomyelin Phosphodiesterase
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pubmed:year |
2002
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pubmed:articleTitle |
Interaction with factor associated with neutral sphingomyelinase activation, a WD motif-containing protein, identifies receptor for activated C-kinase 1 as a novel component of the signaling pathways of the p55 TNF receptor.
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pubmed:affiliation |
Institut für Immunologie and I Medizinische Klinik, Christian-Albrechts-Universität Kiel, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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