Source:http://linkedlifedata.com/resource/pubmed/id/16246731
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
|
pubmed:dateCreated |
2005-10-25
|
pubmed:abstractText |
Nerve growth factor (NGF) binding to p75(NTR) influences TrkA signaling, yet the molecular mechanism is unknown. We observe that NGF stimulates TrkA polyubiquitination, which was attenuated in p75(-/-) mouse brain. TrkA is a substrate of tumor necrosis factor receptor-associated factor 6 (TRAF6), and expression of K63R mutant ubiquitin or an absence of TRAF6 abrogated TrkA polyubiquitination and internalization. NGF stimulated formation of a TrkA/p75(NTR) complex through the p62 scaffold, recruiting the E3/TRAF6 and E2/UbcH7. Peptide targeted to the TRAF6 binding site present in p62 blocked interaction with TRAF6 and inhibited ubiquitination of TrkA, signaling, internalization, and NGF-dependent neurite outgrowth. Mutation of K485 to R blocked TRAF6 and NGF-dependent polyubiquitination of TrkA, resulting in retention of the receptor on the membrane and an absence in activation of specific signaling pathways. These findings reveal that polyubiquitination serves as a common platform for the control of receptor internalization and signaling.
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Lysine,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Polyubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, trkA,
http://linkedlifedata.com/resource/pubmed/chemical/TNF Receptor-Associated Factor 6
|
pubmed:status |
MEDLINE
|
pubmed:month |
Oct
|
pubmed:issn |
1097-2765
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
28
|
pubmed:volume |
20
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
301-12
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:16246731-Animals,
pubmed-meshheading:16246731-Cell Line,
pubmed-meshheading:16246731-Humans,
pubmed-meshheading:16246731-Lysine,
pubmed-meshheading:16246731-Mice,
pubmed-meshheading:16246731-Mice, Knockout,
pubmed-meshheading:16246731-Models, Biological,
pubmed-meshheading:16246731-Nerve Growth Factors,
pubmed-meshheading:16246731-PC12 Cells,
pubmed-meshheading:16246731-Polyubiquitin,
pubmed-meshheading:16246731-Rats,
pubmed-meshheading:16246731-Receptor, trkA,
pubmed-meshheading:16246731-Signal Transduction,
pubmed-meshheading:16246731-Structure-Activity Relationship,
pubmed-meshheading:16246731-TNF Receptor-Associated Factor 6
|
pubmed:year |
2005
|
pubmed:articleTitle |
Lysine 63 polyubiquitination of the nerve growth factor receptor TrkA directs internalization and signaling.
|
pubmed:affiliation |
Department of Biological Sciences, Program in Cellular and Molecular Biosciences, Auburn University, Auburn, Alabama 36849, USA.
|
pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|