Gα_q-mediated plasma membrane translocation of sphingosine kinase-1 and cross-activation of S1P receptors

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• 作者：Michael ter Braak ; Kerstin Danneberg ; Karin Lichte ; Kerstin Liphardt ; Nicholas T. Ktistakis ; Stuart M. Pitson ; Timothy Hla ; Karl H. Jakobs ; Dagmar Meyer zu Heringdorf
• 关键词：Sphingosine-1-phosphate ; Sphingosine kinase ; G-protein-coupled receptor ; G_q ; Plasma membrane translocation ; Receptor cross-activation
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：2009
• 出版时间：May 2009
• 年：2009
• 卷：1791
• 期：5
• 页码：357-370
• 全文大小：2832 K

文摘

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 S1P'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 α-subunits specifically of the G_q family. Classical G_q signalling pathways, or phosphorylation at Ser²²⁵, phospholipase D and Ca²⁺/calmodulin were not involved in M₃ receptor-induced SphK1 translocation in HEK-293 cells. Translocation was associated with S1P receptor internalization, which was dependent on catalytic activity of SphK1 and S1P receptor binding and thus resulted from S1P receptor cross-activation. It is concluded that SphK1 is an important effector of G_q-coupled receptors, linking them via cross-activation of S1P receptors to G_i and G_12/13 signalling pathways.