Gαq-mediated plasma membrane translocation of sphingosine kinase-1 and cross-activation of S1P receptors
Gαq-mediated plasma membrane translocation of sphingosine kinase-1 and cross-activation of S1P receptors
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DOI：
10.1016/j.bbalip.2009.01.019
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发表时间：
2009-05-01
影响因子：
4.8
通讯作者：
Heringdorf, Dagmar Meyer zu
中科院分区：
文献类型：
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作者：
ter Braak, Michael;Danneberg, Kerstin;Heringdorf, Dagmar Meyer zu
1-磷酸鞘氨醇 (S1P) 由鞘氨醇激酶 (SphK) 形成，通过作为特定受体的激动剂或在细胞内调节细胞增殖和迁移。由于 SIP 的作用可能依赖于其形成和降解的亚细胞定位，因此我们研究了 G 蛋白偶联受体对 SphK1 定位的影响。 G(q) 偶联受体的激活诱导 SphK1 深刻、快速（半衰期 3-5 秒）且持久（>2 小时）易位至质膜。这是通过组成型活性 G 蛋白 α 亚基（特别是 G(q) 家族）的表达来模拟的。 HEK-293 细胞中经典的 G(q) 信号通路或 Ser(225)、磷脂酶 D 和 Ca2+/钙调蛋白的磷酸化不参与 M-3 受体诱导的 SphK1 易位。易位与S1P受体内化相关，其依赖于SphK1和SIP受体结合的催化活性，因此是SIP受体交叉激活的结果。结论是SphK1是G(q)偶联受体的重要效应子，通过SIP受体与G(i)和G(12/13)信号通路的交叉激活将它们连接起来。 (C) 2009 Elsevier B.V. 保留所有权利。
Sphingosine-1-phosphate (S1P), formed by sphingosine kinases (SphKs), regulates cellular proliferation and migration by acting as an agonist at specific receptors or intracellularly Since SIP's effects are probably dependent on subcellular localization of its formation and degradation, we have studied the influence of G protein-coupled receptors on the localization of SphK1. Activation of G(q)-coupled receptors induced a profound, rapid (half-life 3-5 s) and long-lasting (>2 h) translocation of SphK1 to the plasma membrane. This was mimicked by expression of constitutively active G protein alpha-subunits specifically of the G(q) family. Classical G(q) signalling pathways, or phosphorylation at Ser(225), phospholipase D and Ca2+/calmodulin were not involved in M-3 receptor-induced SphK1 translocation in HEK-293 cells. Translocation was associated with S1P receptor internalization, which was dependent on catalytic activity of SphK1 and SIP receptor binding and thus resulted from SIP receptor cross-activation. It is concluded that SphK1 is an important effector of G(q)-coupled receptors, linking them via cross-activation of SIP receptors to G(i) and G(12/13) signalling pathways. (C) 2009 Elsevier B.V. All rights reserved.