Neutral Sphingomyelinase 2 Activity and Protein Stability Are Modulated by Phosphorylation of Five Conserved Serines
Neutral Sphingomyelinase 2 Activity and Protein Stability Are Modulated by Phosphorylation of Five Conserved Serines
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DOI：
10.1074/jbc.m111.315481
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发表时间：
2012-01-02
影响因子：
4.8
通讯作者：
Goldkorn, Tzipora
中科院分区：
文献类型：
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作者：
Filosto, Simone;Ashfaq, Majid;Goldkorn, Tzipora
我们之前提出，中性鞘磷脂酶2 （nSMase2）是暴露于氧化应激（ox-应激）后，人类气道上皮（HAE）细胞中唯一激活的SMase，产生神经酰胺积累，从而诱导细胞凋亡。此外，我们报道了nSMase2是一种磷酸化蛋白，其磷酸化水平控制着氧化应激诱导的nSMase2激活。在这里，我们确定了在nSMase2中磷酸化的五个特定丝氨酸，并证明它们的磷酸化以一种相互依赖的方式控制着缺氧胁迫暴露时nSMase2的活性。此外，我们发现nSMase2蛋白的稳定性及其表达水平也受到这五个丝氨酸磷酸化位点的翻译后调控。该研究提供了关于nSMase2磷酸化位点的初步结构/功能见解，并为未来旨在充分阐明nSMase2调控机制的研究提供了一些新的联系。
We previously presented that the neutral sphingomyelinase 2 (nSMase2) is the only SMase activated in human airway epithelial (HAE) cells following exposure to oxidative stress (ox-stress), yielding ceramide accumulation and thereby inducing apoptosis. Furthermore, we reported that nSMase2 is a phospho-protein in which the level of phosphorylation controls nSMase2 activation induced by ox-stress. Here we identify five specific serines that are phosphorylated in nSMase2 and demonstrate that their phosphorylation controls the nSMase2 activity upon ox-stress exposure in an interdependent manner. Furthermore, we show that the nSMase2 protein stability and thus its level of expression is also post-translationally regulated by these five serine phosphorylation sites. This study provides initial structure/function insights regarding nSMase2 phosphorylation sites and offers some new links for future studies aiming to fully elucidate nSMase2 regulatory machinery.