Ligand-induced nuclear translocation of S1P(1) receptors mediates Cyr61 and CTGF transcription in endothelial cells.

Ligand-induced nuclear translocation of S1P(1) receptors mediates Cyr61 and CTGF transcription in endothelial cells.
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DOI:
10.1007/s00418-008-0521-9
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发表时间:
2009-02
影响因子:
2.3
通讯作者:
Lee, Menq-Jer
Lee, Menq-Jer
中科院分区:
生物学3区
文献类型:
--
作者:
Estrada, Rosendo;Wang, Lichun;Jala, Venkatakrishna R.;Lee, Jen-Fu;Lin, Cheng-Yon;Gray, Robert D.;Haribabu, Bodduluri;Lee, Menq-Jer

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1-磷酸鞘氨醇(S1 P)受体亚型1(S1 P1)是一种G蛋白偶联受体(GPCR),调节内皮细胞(EC)的多种生物学活性。在这份报告中,我们表明,S1 P1受体存在于细胞的细胞核中,通过使用各种生化和显微镜技术,如细胞分级分离,免疫金标记,共聚焦显微镜分析。活细胞成像显示,质膜S1 P1受体被迅速内化,随后易位到核隔室后S1 P刺激。利用膜生物素化技术进一步支持了核S1 P1受体在配体处理后从质膜S1 P1内化的观点。此外,核S1 P1能够调节Cyr 61和CTGF的转录,这两种生长因子在脉管系统的调节中具有重要的功能。这些数据表明,在内皮细胞的核区室中存在一种新的S1 P-S1 P1信号轴,其可能调节内皮细胞的生物学反应。
Sphingosine-1-phosphate (S1P) receptor subtype 1 (S1P1), a G-protein coupled receptor (GPCR), regulates many biological activities of endothelial cells (ECs). In this report, we show that S1P1 receptors are present in the nuclei of ECs by using various biochemical and microscopic techniques such as cellular fractionation, immunogold labeling, and confocal microscopic analysis. Live cell imaging showed that plasma membrane S1P1 receptors are rapidly internalized and subsequently translocated to nuclear compartment upon S1P stimulation. Utilizing membrane biotinylation technique further supports the notion that nuclear S1P1 receptors were internalized from plasma membrane S1P1 after ligand treatment. Moreover, nuclear S1P1 is able to regulate the transcription of Cyr61 and CTGF, two growth factors functionally important in the regulation of vasculature. Collectively, these data suggest a novel S1P–S1P1 signaling axis present in the nuclear compartment of endothelial cells, which may regulate biological responses of endothelium.
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