Abstract
Contribution of sphingosine kinase (SPK)-catalyzed production of sphingosine-1-phosphate (SPP), in comparison to phospholipase C (PLC), to Ca(2+) signalling by epidermal growth factor (EGF) was studied in two HEK-293 cell clones (HEK2 and HEK3), expressing functional EGF receptors and exhibiting release of stored Ca(2+) by intracellular SPP. In HEK3 cells, EGF increased [Ca(2+)](i) and stimulated both, SPK and PLC. [Ca(2+)](i) increase, but not PLC stimulation, was strongly reduced by SPK inhibition. In HEK2 cells, EGF similarly stimulated PLC, but did not increase [Ca(2+)](i) or stimulate SPK, suggesting that intracellular SPP production plays a major role for Ca(2+) signalling by EGF in HEK-293 cells.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Calcium Signaling / drug effects
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Calcium Signaling / physiology*
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Cell Line
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Enzyme Activation
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Epidermal Growth Factor / pharmacology
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ErbB Receptors / physiology*
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Humans
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Inositol 1,4,5-Trisphosphate / metabolism
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Kidney
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Lysophospholipids*
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MAP Kinase Signaling System / drug effects
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Phosphatidylinositol Diacylglycerol-Lyase
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Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
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Phosphotransferases (Alcohol Group Acceptor) / physiology*
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Receptors, Muscarinic / metabolism
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Sphingosine / analogs & derivatives
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Sphingosine / metabolism
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Type C Phospholipases / metabolism
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Virulence Factors, Bordetella / pharmacology
Substances
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Lysophospholipids
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Receptors, Muscarinic
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Virulence Factors, Bordetella
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sphingosine 1-phosphate
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Epidermal Growth Factor
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Inositol 1,4,5-Trisphosphate
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Phosphotransferases (Alcohol Group Acceptor)
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sphingosine kinase
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ErbB Receptors
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Type C Phospholipases
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Phosphatidylinositol Diacylglycerol-Lyase
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Sphingosine