Role of sphingosine kinase in Ca2+ signalling by epidermal growth factor receptor

• DOI: 10.1016/s0014-5793(99)01463-5
• Publication Date: 2002-07-25T13:52:28Z
• Authors: Dagmar Meyer zu H...; Holger Lass; Igor Kuchar; Regina Alemany; Yuanjian Guo; Martina Schmidt; Karl H Jakobs
• Keywords: 0303 health sciences; Epidermal Growth Factor; MAP Kinase Signaling System; Phosphatidylinositol Diacylglycerol-Lyase; Epidermal growth factor; Inositol 1,4,5-Trisphosphate; Kidney; Receptors, Muscarinic; Cell Line; Sphingosine kinase; Enzyme Activation; ErbB Receptors; Phosphotransferases (Alcohol Group Acceptor); 03 medical and health sciences; Phospholipase C; Sphingosine; Ca2+ signalling; Type C Phospholipases; Humans; Calcium Signaling; Virulence Factors, Bordetella; Lysophospholipids

Contribution of sphingosine kinase (SPK)‐catalyzed production of sphingosine‐1‐phosphate (SPP), in comparison to phospholipase C (PLC), to Ca2+ 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 Ca2+ by intracellular SPP. In HEK3 cells, EGF increased [Ca2+]i and stimulated both, SPK and PLC. [Ca2+]i increase, but not PLC stimulation, was strongly reduced by SPK inhibition. In HEK2 cells, EGF similarly stimulated PLC, but did not increase [Ca2+]i or stimulate SPK, suggesting that intracellular SPP production plays a major role for Ca2+ signalling by EGF in HEK‐293 cells.