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Andree Blaukat, Ivan Dikic

Activation of Sphingosine Kinase by the Bradykinin B2 Receptor and Its Implication in Regulation of the ERK/MAP Kinase Pathway

Sphingosine kinase phosphorylates sphingosine to generate sphingosine 1-phosphate, a phospholipid that has been implicated in signaling by a number of transmembrane receptors and was recently shown to act as a ligand for a specific class of G protein-coupled receptors. Here we show that the G protein-coupled bradykinin B₂ receptor activates sphingosine kinase leading to a time- and dose-dependent elevation of cellular sphingosine 1-phosphate levels that was blocked by the sphingosine kinase inhibitor dihydrosphingosine. Furthermore, increasing doses of this inhibitor partially affected the bradykinin-mediated ERK/MAP kinase activation and fully blocked the protein kinase C-independent component of the signaling pathway from the B₂ receptor to the ERK/MAP kinase cascade. Overexpression of sphingosine kinase did not additionally increase the bradykinin-induced ERK/MAP kinase activity, indicating a permissive rather than activating role of sphingosine 1-phosphate in B₂ receptor-mediated mitogenic signaling.

Biological Chemistry, Walter de Gruyter

Print ISSN: 1431-6730
Volume: 382, 02/2001
Pages: 135 - 139

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