The intracellular action of sphingosine 1-phosphate in GPVI-mediated Ca2+ mobilization in platelets.
We analyzed the intracellular action of sphingosine 1-phosphate (Sph-1-P), formed from sphingosine (Sph) by sphingosine kinase (SPHK), in platelets. When sphingosine kinase activity was inhibited by N,N-dimethylsphingosine (DMS), Ca2+ mobilization induced by convulxin, an agonist of the collagen receptor glycoprotein VI (GPVI), was moderately but specifically abolished; that induced via G protein-coupled receptors was not affected. Under the same conditions, however, tyrosine phosphorylation of Syk and phospholipase Cgamma2, which is essential for the GPVI-mediated signaling, was not inhibited. Sphingosine kinase activity of the platelet membrane fraction increased specifically upon stimulation with convulxin or collagen. Our results suggest that intracellular sphingosine 1-phosphate is related to Ca2+ mobilization in GPVI-mediated signaling pathways.
Ohmori
T
T
Department of Laboratory Medicine, University of Yamanashi Faculty of Medicine, 1110 Shimokato, Tamaho, Yamanashi 409-3898, Japan.
Yatomi
Y
Y
Osada
M
M
Ozaki
Y
Y
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D003094:Collagen / Q000494:pharmacology; D003435:Crotalid Venoms / Q000494:pharmacology; D006801:Humans; D037181:Lectins, C-Type; D008246:Lysophospholipids / Q000097:blood / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000819:agonists / Q000378:metabolism*; D018179:Receptors, Thrombin / Q000737:chemistry; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D014443:Tyrosine / Q000187:drug effects / Q000378:metabolism; D000099157:Sphingosine Kinase
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002118:Calcium; D003094:Collagen; D003435:Crotalid Venoms; D037181:Lectins, C-Type; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D010980:Platelet Membrane Glycoproteins; D018179:Receptors, Thrombin; D013110:Sphingosine; D014443:Tyrosine; D000099157:Sphingosine Kinase; C098341:platelet membrane glycoprotein VI; C060506:sphingosine 1-phosphate; C028890:convulxin; C061800:N,N-dimethylsphingosine