Calcium mobilization via sphingosine kinase in signalling by the FcεRI antigen receptor

O. H. Choi, J. H. Kim, J. P. Kinet

Research output: Contribution to journalArticle

Abstract

Calcium mobilization through antigen receptors, including high-affinity IgE receptors (FcεRI), is thought to be mediated by inositol-1,4,5-trisphosphate production (InsP3). Here we show that antigen clustering of FcεRI on the rat mast-cell line (RBL-2H3) activates a sphingosine kinase (SK) and produces sphingosine-1-phosphate (S1P), an alternative second messenger for intracellular calcium mobilization. The sphingosine analogue, D-L-threo-dihydrosphingosine (DHS), inhibits the SK enzyme competitively with a dissociation constant, K(i) of 5 to 18 μM. This inhibition substantially suppresses the FcεRI-mediated calcium signal, but leaves intact the syk tyrosine kinase activation and the small InsP3 production. The entire InsP3 dependent pathway activated by a transfected G-protein coupled receptor, used here as a positive control, also remained intact. Thus FcεRI principally utilizes a SK pathway to mobilize calcium.

Original languageEnglish (US)
Pages (from-to)634-636
Number of pages3
JournalNature
Volume380
Issue number6575
DOIs
StatePublished - May 1 1996

ASJC Scopus subject areas

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