Identification of functional nuclear export sequences in human sphingosine kinase 1
Identification of functional nuclear export sequences in human sphingosine kinase 1
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DOI：
10.1016/j.bbrc.2003.09.194
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发表时间：
2003-11-07
影响因子：
3.1
通讯作者：
Igarashi, Y
中科院分区：
文献类型：
--
作者：
Inagaki, Y;Li, PY;Igarashi, Y
鞘氨醇激酶（SPHK）是一种将鞘氨醇磷酸化形成鞘氨醇I-磷酸（SIP）的酶。人SPHK 1（hSPHK 1）在Cos 7细胞中瞬时表达时主要定位于细胞质中。在本研究中，我们在hSPHK 1的中间区域发现了两个功能性的核输出信号（内斯）序列。缺失和突变研究表明，SPHK 1的细胞质定位取决于其核输出，由内斯指导。此外，在用核输出受体CRM 1的特异性抑制剂来普霉素B处理后，观察到hSPHK 1的显著核积累，表明hSPHK 1在细胞质和细胞核之间穿梭。我们的研究结果提供了SPHK 1活性核输出的第一个证据，并表明它是由CRM 1依赖性途径介导的。(C)2003年爱思唯尔公司All rights reserved.
Sphingosine kinase (SPHK) is an enzyme that phosphorylates sphingosine to form sphingosine I-phosphate (SIP). Human SPHK1 (hSPHK1) was localized predominantly in the cytoplasm when transiently expressed in Cos7 cells. In this study, we have found two functional nuclear export signal (NES) sequences in the middle region of hSPHK1. Deletion and mutagenesis studies revealed that the cytoplasmic localization of SPHK1 depends on its nuclear export, directed by the NES. Furthermore, upon treatment with leptomycin B, a specific inhibitor of the nuclear export receptor CRM1, a marked nuclear accumulation of hSPHK1 was observed, indicating that hSPHK1 shuttles between the cytoplasm and the nucleus. Our results provide the first evidence of the active nuclear export of SPHK1 and suggest it is mediated by a CRM1-dependent pathway. (C) 2003 Elsevier Inc. All rights reserved.