PKA phosphorylates the p75 receptor and regulates its localization to lipid rafts
PKA phosphorylates the p75 receptor and regulates its localization to lipid rafts
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DOI：
10.1093/emboj/cdg177
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发表时间：
2003-04-15
期刊：
影响因子：
11.4
通讯作者：
Tohyama, M
中科院分区：
文献类型：
--
作者：
Higuchi, H;Yamashita, T;Tohyama, M
尽管对常见神经营养因子受体p75（NTR）介导的多种作用进行了大量研究，但对p75（NTR）启动细胞内信号转导的分子机制知之甚少。我们发现了camp依赖性蛋白激酶(pkacβ) β催化亚基的一个变体，作为p75（NTR）相互作用蛋白，它使p75（NTR）的Ser304磷酸化。小脑神经元细胞内cAMP通过与p75（NTR）的配体结合而短暂积累。cAMP-PKA的激活是p75（NTR）向脂质筏转运以及p75（NTR）的生化和生物活性（如Rho的失活和神经突的生长）所必需的。激活的p75（NTR）在脂质筏（代表特殊信号细胞器的结构）上的适当募集对于确定p75（NTR）的生物活性至关重要。
Although a large number of studies have been carried out on the diverse effects mediated by the common neurotrophin receptor p75(NTR), little is known about the molecular mechanisms by which p75(NTR) initiates intracellular signal transduction. We identified a variant of the beta catalytic subunit of cAMP-dependent protein kinase (PKACbeta) as a p75(NTR)-interacting protein, which phosphorylates p75(NTR) at Ser304. Intracellular cAMP in cerebellar neurons was accumulated transiently by ligand binding to p75(NTR). Activation of cAMP-PKA is required for translocation of p75(NTR) to lipid rafts, and for biochemical and biological activities of p75(NTR), such as inactivation of Rho and the neurite outgrowth. Proper recruitment of activated p75(NTR) to lipid rafts, structures that represent specialized signaling organelles, is of fundamental importance in determining p75(NTR) bioactivity.