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Activation of Sphingosine Kinase by the Bradykinin B2 Receptor and Its Implication in Regulation of the ERK/MAP Kinase Pathway
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Andree Blaukat
Published/Copyright:
July 5, 2005
Abstract
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.
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Published Online: 2005-07-05
Published in Print: 2001-01-06
Copyright © 2001 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- To Our Authors, Readers and Subscribers
- Kinins 1925-2000
- The Expanded Human Kallikrein (KLK) Gene Family: Genomic Organisation, Tissue-Specific Expression and Potential Functions
- Novel Roles of Kallistatin, a Specific Tissue Kallikrein Inhibitor, in Vascular Remodeling
- Signal Transduction from Bradykinin, Angiotensin, Adrenergic and Muscarinic Receptors to Effector Enzymes, Including ADP-Ribosyl Cyclase
- Classification of Kinin Receptors
- Metabolism-Resistant Bradykinin Antagonists: Development and Applications
- Kinins, Receptors, Kininases and Inhibitors Where Did They Lead Us?
- Bradykinin Signalling to MAP Kinase: Cell-Specific Connections versus Principle Mitogenic Pathways
- Kinins and Epithelial Ion Transport in the Alimentary Tract
- Role of the Renal Kallikrein-Kinin System in the Development of Salt-Sensitive Hypertension
- Role of the Light Chain of High Molecular Weight Kininogen in Adhesion, Cell-Associated Proteolysis and Angiogenesis
- Activation of the Kinin-Forming Cascade on the Surface of Endothelial Cells
- Kallikrein and Kinin Receptor Expression in Inflammation and Cancer
- Altered Neutrophil Homeostasis in Kinin B1 Receptor-Deficient Mice
- Cystatins as Calpain Inhibitors: Engineered Chicken Cystatin- and Stefin B-Kininogen Domain 2 Hybrids Support a Cystatin-Like Mode of Interaction with the Catalytic Subunit of µ-Calpain
- Synthetic Peptides and Fluorogenic Substrates Related to the Reactive Site Sequence of Kunitz-Type Inhibitors Isolated from Bauhinia: Interaction with Human Plasma Kallikrein
- Identification and Characterization of an Aromatic Amino Acid Decarboxylase from the Filarial Nematode, Dirofilaria immitis
- Molecular Cloning and Pharmacological Characterization of the Canine B1 and B2 Bradykinin Receptors
- Ligand-Mediated Regulation of Kinin Receptors in the Rabbit
- Activation of Sphingosine Kinase by the Bradykinin B2 Receptor and Its Implication in Regulation of the ERK/MAP Kinase Pathway
