Involvement of pertussis toxin‐sensitive GTP‐binding proteins in sphingosine 1‐phosphate‐induced activation of phospholipase CCa2+ system in HL60 leukemia cells

FEBS Letters

Nochi, Hiromi¹  Tamoto, Koichi¹  Tomura, Hideaki²  Sho, Kimie²  Kondo, Yoichi²  Okajima, Fumikazu² 

[1] Department of Microbiology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0, Japan;Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371, Japan

关键词: Spingosine 1-phosphate;    GTP-binding protein;    Phospholipase C;    HL60 cell;    S1P;    sphingosine 1-phosphate;    PTX;    pertussis toxin;    [Ca2+]i;    cytoplasmic free Ca2+ concentration;    G-protein;    GTP-binding regulatory protein;    Hepes;    4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid;    PMA;    phorbol 12-myristate 13-acetate;    EGTA;    (ethylenebis(oxyethylenenitrilo))tetraacetic acid;    IP2;    inositol bisphosphate;    IP3;    inositol trisphosphate;    fMLP;    formyl-Met-Leu-Phe;   

DOI  :  10.1016/0014-5793(95)01526-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Exogenous sphingosine 1-phosphate (S1P) induced Ca²⁺ mobilization, in association with an increase in inositol polyphosphate production reflecting activation of phospholipase C in HL60 leukemia cells. The increase in intracellular Ca²⁺ concentration ([Ca²⁺]_i) induced by S1P was inhibited by an appropriate treatment of the cells with pertussis toxin (PTX), U73122 (a phospholipase C inhibitor) or phorbol 12-myristate 13-acetate (PMA). In parallel with the Ca²⁺ response, these agents also inhibited inositol polyphosphate production. The S1P-induced Ca²⁺ response was also attenuated in the dibutyryl cAMP-induced differentiated cells, where GTP-binding protein-induced Ca²⁺ response is suggested to be enhanced. Lysophosphatidic acid (LPA) also increased [Ca²⁺]_i in the cells, but the maximal response was about half of that of S1P, and furthermore PTX and dibutyryl cAMP treatment hardly affected the LPA-induced Ca²⁺ mobilization. We conclude that exogenous S1P mobilizes Ca²⁺ through phospholipase C activation. The S1P-induced enzyme activation is at least partly mediated by PTX-sensitive GTP-binding protein-coupled receptors which may be different from LPA receptors.

【 授权许可】

Unknown