Intracellular calcium release mediated by sphingosine derivatives generated in cells.
Soluble and hydrophobic lipid breakdown products have a variety of important signaling roles in cells. Here sphingoid bases derived in cells from sphingolipid breakdown are shown to have a potent and direct effect in mediating calcium release from intracellular stores. Sphingosine must be enzymically converted within the cell to a product believed to be sphingosine-1-phosphate, which thereafter effects calcium release from a pool including the inositol 1,4,5-trisphosphate-sensitive calcium pool. The sensitivity, molecular specificity, and reversibility of the effect on calcium movements closely parallel sphingoid base-mediated inhibition of protein kinase C. Generation of sphingoid bases in cells may activate a dual signaling pathway involving regulation of calcium and protein kinase C, comparable perhaps to the phosphatidylinositol and calcium signaling pathway.
Ghosh
T K
TK
Department of Biological Chemistry, University of Maryland School of Medicine, Baltimore 21201.
Bian
J
J
Gill
D L
DL
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D007700:Kinetics; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013816:Thermodynamics
C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D000001:Calcimycin; D000244:Adenosine Diphosphate; D011493:Protein Kinase C; C023553:mannose-6-phosphatase; D010744:Phosphoric Monoester Hydrolases; D013110:Sphingosine; D002118:Calcium