title: Involvement of pertussis toxin-sensitive GTP-binding proteins in sphingosine 1-phosphate-induced activation of phospholipase C-Ca2+ system in HL60 leukemia cells.
abstract: 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 suggested to be enhanced. Lysophosphatidic acid (LPA) also increased [Ca2+]i in the cels, 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.
authors.affiliation: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Okajima
authors.forename: H
authors.initials: H
authors.lastname: Tomura
authors.forename: K
authors.initials: K
authors.lastname: Sho
authors.forename: H
authors.initials: H
authors.lastname: Nochi
authors.forename: K
authors.initials: K
authors.lastname: Tamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kondo
mesh_terms: D002118:Calcium / Q000378:metabolism*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D007938:Leukemia; D008246:Lysophospholipids; D037342:Pertussis Toxin; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000378:metabolism*
chemical_list: D007295:Inositol Phosphates; D008246:Lysophospholipids; D010566:Virulence Factors, Bordetella; C060506:sphingosine 1-phosphate; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D013110:Sphingosine; D002118:Calcium