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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >P48 Ebp1 acts as a downstream mediator of Trk signaling in neurons, contributing neuronal differentiation.
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P48 Ebp1 acts as a downstream mediator of Trk signaling in neurons, contributing neuronal differentiation.

机译：P48 Ebp1充当神经元Trk信号的下游介质，促进神经元分化。

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摘要

Two Ebp1 isoproteins, p48 and p42, regulate cell survival and differentiation distinctively. Here we show that p48 is the major isoform in hippocampal neurons and is localized throughout the entire neuron. Notably, reduction of p48 Ebp1 expression inhibited BDNF-mediated neurite outgrowth in hippocampal neurons. The p48 protein acts as a downstream effector of the Trk receptor, which mediates the functions of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in hippocampal cells. Trk receptor activation by both NGF and BDNF induced phosphorylation of Ebp1 at the S360 upon the activation of protein kinase Cdelta (PKCdelta) and triggered dissociation of p48 from retinoblastoma (Rb). Although both NGF and BDNF activate mitogen-activated protein kinase (MAPK; extracellular signal-related kinase (ERK)) as well as phosphatidylinositide 3-kinase (PI3K)/Akt, their activation is regulated in different time-frame upon growth factor specificity, especially, eliciting PKCdelta mediated p48 S360 phosphorylation. Thus, p48 Ebp1 contributes to neuronal cell differentiation and growth factor specificity through the activation of PKCdelta, acting as a crucial downstream effector of neurotrophin signaling.
机译：两种Ebp1异蛋白p48和p42分别调节细胞存活和分化。在这里，我们显示p48是海马神经元中的主要同工型，并且位于整个神经元中。值得注意的是，p48 Ebp1表达的减少抑制了海马神经元中BDNF介导的神经突生长。 p48蛋白充当Trk受体的下游效应物，其介导海马细胞中神经生长因子（NGF）和脑源性神经营养因子（BDNF）的功能。 Nrk和BDNF激活Trk受体后，蛋白激酶Cdelta（PKCdelta）激活后，S360处Ebp1磷酸化，并引发视网膜母细胞瘤（Rb）分离p48。尽管NGF和BDNF均可激活促分裂原激活的蛋白激酶（MAPK;细胞外信号相关激酶（ERK））以及磷脂酰肌醇3激酶（PI3K）/ Akt，但它们的激活在不同时间范围内受生长因子特异性的调节，尤其是引起PKCdelta介导的p48 S360磷酸化。因此，p48 Ebp1通过激活PKCdelta来促进神经元细胞分化和生长因子特异性，而PKCdelta是神经营养蛋白信号传导的关键下游效应子。

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