
Target‐derived neurotrophins regulate neuronal survival and growth by interacting with cell‐surface tyrosine kinase receptors. The p75 neurotrophin receptor (p75NTR) is coexpressed with Trk receptors in long‐range projection neurons, in which it facilitates neurotrophin binding to Trk and enhances Trk activity. Here, we show that TrkA and TrkB receptors undergo robust ligand‐dependent ubiquitination that is dependent on activation of the endogenous Trk activity of the receptors. Coexpression of p75NTR attenuated ubiquitination of TrkA and TrkB and delayed nerve growth factor‐induced TrkA receptor internalization and receptor degradation. These results indicate that p75NTR may prolong cell‐surface Trk‐dependent signalling events by negatively regulating receptor ubiquitination.
Neurons, Ubiquitin, Brain-Derived Neurotrophic Factor, Immunoblotting, Transfection, PC12 Cells, Receptor, Nerve Growth Factor, Rats, Nerve Growth Factor, Animals, Humans, Immunoprecipitation, Receptor, trkB, Electrophoresis, Polyacrylamide Gel, Receptor, trkA, Cells, Cultured, Signal Transduction
Neurons, Ubiquitin, Brain-Derived Neurotrophic Factor, Immunoblotting, Transfection, PC12 Cells, Receptor, Nerve Growth Factor, Rats, Nerve Growth Factor, Animals, Humans, Immunoprecipitation, Receptor, trkB, Electrophoresis, Polyacrylamide Gel, Receptor, trkA, Cells, Cultured, Signal Transduction
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