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Type: Journal article
Title: G alpha(q)-mediated plasma membrane translocation of sphingosine kinase-1 and cross-activation of S1P receptors
Author: ter Braak, M.
Danneberg, K.
Lichte, K.
Liphardt, K.
Ktistakis, N.
Pitson, S.
Hla, T.
Jakobs, K.
Meyer zu Heringdorf, D.
Citation: BBA: Molecular and Cell Biology of Lipids, 2009; 1791(5):357-370
Publisher: Elsevier Science BV
Issue Date: 2009
ISSN: 1388-1981
Statement of
Michael ter Braak, Kerstin Danneberg, Karin Lichte, Kerstin Liphardt, Nicholas T. Ktistakis, Stuart M. Pitson, Timothy Hla, Karl H. Jakobs and Dagmar Meyer zu Heringdorf
Abstract: 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 Gq-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 Gq family. Classical Gq 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 Gq-coupled receptors, linking them via cross-activation of S1P receptors to G(i) and G12/13 signalling pathways.
Keywords: Sphingosine-1-phosphate
Sphingosine kinase
G-protein-coupled receptor
Plasma membrane translocation
Receptor cross-activation
Rights: © 2009 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.bbalip.2009.01.019
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Molecular and Biomedical Science publications

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