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Association of the p75 Neurotrophin Receptor with TRAF6
In addition to the Trk tyrosine kinase receptors, neurotrophins also bind to a second receptor, p75, a member of the tumor necrosis factor receptor superfamily. Several signaling pathways have been implicated for p75 in the absence of Trk receptors, including induction of NF-κB and c-Jun kinase act...
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Published in: | The Journal of biological chemistry 1999-01, Vol.274 (5), p.2597-2600 |
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Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | In addition to the Trk tyrosine kinase receptors, neurotrophins also bind to a second receptor, p75, a member of the tumor
necrosis factor receptor superfamily. Several signaling pathways have been implicated for p75 in the absence of Trk receptors,
including induction of NF-κB and c-Jun kinase activities and increased production of ceramide. However, to date, the mechanisms
by which the p75 receptor initiates intracellular signal transduction have not been defined. Here we report a specific interaction
between p75 and TRAF6 ( t umor necrosis factor r eceptor- a ssociated f actor-6) after transient transfection in HEK293T cells. The interaction was ligand-dependent and maximal at 100 ng/ml of nerve
growth factor (NGF). Other neurotrophins also promoted the association of TRAF6 with p75 but to a lesser extent. The binding
of TRAF6 was localized to the juxtamembrane region of p75 by co-immunoprecipitation and Western blotting. To assess the functional
significance of this interaction, we have tested responses in cultured Schwann cells that express p75 and TRAF6. An NGF-mediated
increase in the nuclear localization of the p65 subunit of NF-κB could be blocked by the introduction of a dominant negative
form of TRAF6 in Schwann cells. These results indicate that TRAF6 can potentially function as a signal transducer for NGF
actions through the p75 receptor. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.274.5.2597 |