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Activation of sphingosine kinase by the bradykinin B2 receptor and its implication in regulation of the ERK/MAP kinase pathway.
Ludwiginstitutet för Cancerforskning.
2001 (English)In: Biol Chem, ISSN 1431-6730, Vol. 382, no 1, 135-9 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2001. Vol. 382, no 1, 135-9 p.
Keyword [en]
Enzyme Activation/physiology, Enzyme Inhibitors/pharmacology, Gene Expression Regulation; Enzymologic/genetics, Humans, Lysophospholipids, Mitogen-Activated Protein Kinases/biosynthesis/genetics/*metabolism, Phosphotransferases (Alcohol Group Acceptor)/antagonists & inhibitors/*metabolism, Receptor; Bradykinin B2, Receptors; Bradykinin/*physiology, Research Support; Non-U.S. Gov't, Signal Transduction/drug effects/physiology, Sphingosine/*analogs & derivatives/biosynthesis/pharmacology
URN: urn:nbn:se:uu:diva-73601PubMedID: 11258664OAI: oai:DiVA.org:uu-73601DiVA: diva2:101511
Available from: 2005-06-10 Created: 2005-06-10 Last updated: 2011-01-13

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ReferencesLink to record
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