p75 neurotrophin receptor reduces ligand-induced Trk receptor ubiquitination and delays Trk receptor internalization and degradation
p75 neurotrophin receptor reduces ligand-induced Trk receptor ubiquitination and delays Trk receptor internalization and degradation
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DOI：
10.1038/sj.embor.7400503
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发表时间：
2005-10-01
期刊：
影响因子：
7.7
通讯作者：
Barker, PA
中科院分区：
文献类型：
--
作者：
Makkerh, JPS;Ceni, C;Barker, PA
靶源性神经营养因子通过与细胞表面酪氨酸激酶受体相互作用调节神经元的存活和生长。p75神经营养因子受体（p75NTR）与Trk受体在长距离投射神经元中共表达，其中它促进神经营养因子与Trk结合并增强Trk活性。在这里，我们表明，TrkA和TrkB受体进行强大的配体依赖性泛素化，这是依赖于激活的内源性Trk活性的受体。p75 NTR的共表达减弱了TrkA和TrkB的泛素化，并延迟了神经生长因子诱导的TrkA受体内化和受体降解。这些结果表明，p75 NTR可以延长细胞表面的Trk依赖的信号转导事件负调节受体泛素化。
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.