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

FEBS Letters

Jakobs, Karl H¹  Schmidt, Martina¹  Alemany, Regina¹  Meyer zu Heringdorf, Dagmar¹  Kuchar, Igor¹  Guo, Yuanjian¹  Lass, Holger¹ 

[1] Institut für Pharmakologie, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany

关键词: Epidermal growth factor;    Sphingosine kinase;    Ca2+ signalling;    Phospholipase C;    [Ca2+]i;    cytosolic free Ca2+ concentration;    DHS;    DL-threo-dihydrosphingosine;    EGF;    epidermal growth factor;    GPCR;    G-protein-coupled receptor;    HBSS;    Hanks’ balanced salt solution;    IP3;    myo-inositol 1;    4;    5-trisphospate;    mAChR;    muscarinic acetylcholine receptor;    MAP kinase;    mitogen-activated protein kinase;    PDGF;    platelet-derived growth factor;    PLC;    phospholipase C;    PTX;    pertussis toxin;    SPK;    sphingosine kinase;    SPP;    sphingosine-1-phosphate;   

DOI  :  10.1016/S0014-5793(99)01463-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown