Role of sphingosine kinase in Ca(2+) signalling by epidermal growth factor receptor.
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.
Meyer zu Heringdorf
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Institut für Pharmakologie, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122, Essen, Germany. meyer-heringdorf@uni-essen.de
Lass
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Kuchar
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Alemany
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Guo
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Schmidt
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Jakobs
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D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000502:physiology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007668:Kidney; D008246:Lysophospholipids; D020935:MAP Kinase Signaling System / Q000187:drug effects; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000099157:Sphingosine Kinase
D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D015544:Inositol 1,4,5-Trisphosphate; D008246:Lysophospholipids; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D017853:Phosphotransferases (Alcohol Group Acceptor); D011976:Receptors, Muscarinic; D013110:Sphingosine; D010738:Type C Phospholipases; D010566:Virulence Factors, Bordetella; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate