Calcium mobilization via sphingosine kinase in signalling by the FcɛRI antigen receptor
| Autor: | Oksoon Hong Choi, Jae-Heup Kim, Jean-Pierre Kinet |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Sphingosine kinase
chemistry.chemical_element Inositol 1 4 5-Trisphosphate Biology Calcium Calcium in biology Cell Line Mice chemistry.chemical_compound Cytosol Sphingosine Animals Humans Enzyme Inhibitors Receptor Calcium metabolism Multidisciplinary Receptors IgE 3T3 Cells Protein-Tyrosine Kinases Genistein Isoflavones Receptors Muscarinic Rats Cell biology Enzyme Activation Phosphotransferases (Alcohol Group Acceptor) chemistry Biochemistry Second messenger system Lysophospholipids Signal transduction Signal Transduction |
| Zdroj: | Nature. 380:634-636 |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | Calcium mobilization through antigen receptors, including high-affinity IgE receptors (Fc epsilon RI), is thought to be mediated by inositol-1,4,5-trisphosphate production (InsP3). Here we show that antigen clustering of Fc epsilon RI on the rat mast-cell line (RBL-2H3) activates a sphingosine kinase (SK) and produces sphingosine-1-phosphate (S1P), and alternative second messenger for intracellular calcium mobilization. The sphingosine analogue, D-L-threo-dihydrosphingosine (DHS), inhibits the SK enzyme competitively with a dissociation constant, K1, of 5 to 18 microM. This inhibition substantially suppresses the Fc epsilon RI-mediated calcium signal, but leaves intact the syk tyrosine kinase activation and the small InsP3 production. The entire InsP3-dependent pathway activated by a transfected G-protein coupled receptor, used here as a positive control, also remained intact. Thus Fc epsilon RI principally utilizes a SK pathway to mobilize calcium. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|