Open AccessEarly Activation of Sphingosine Kinase in Mast Cells and Recruitment to FcεRI Are Mediated by Its Interaction with Lyn Kinase
Author(s) -
Nicole Urtz,
Ana Olivera,
Elisa Bofill-Cardona,
Robert Csonga,
Andreas Billich,
Diana Mechtcheriakova,
Frédéric Bornancin,
Max Woisetschläger,
Juan Rivera,
Thomas Baumruker
Publication year - 2004
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.24.19.8765-8777.2004
Subject(s) - lyn , sphingosine kinase 1 , sphingosine , sphingosine kinase , biology , microbiology and biotechnology , degranulation , tyrosine kinase , cyclin dependent kinase 9 , kinase , sphingosine 1 phosphate , sphingolipid , signal transduction , protein kinase a , mitogen activated protein kinase kinase , biochemistry , receptor
Sphingosine kinase has been recognized as an essential signaling molecule that mediates the intracellular conversion of sphingosine to sphingosine-1-phosphate. In mast cells, induction of sphingosine kinase and generation of sphingosine-1-phosphate have been linked to the initial rise in Ca(2+), released from internal stores, and to degranulation. These events either precede or are concomitant with the activation of phospholipase C-gamma and the generation of inositol trisphosphate. Here we show that sphingosine kinase type 1 (SPHK1) interacts directly with the tyrosine kinase Lyn and that this interaction leads to the recruitment of this lipid kinase to the high-affinity receptor for immunoglobulin E (FcepsilonRI). The interaction of SPHK1 with Lyn caused enhanced lipid and tyrosine kinase activity. After FcepsilonRI triggering, enhanced sphingosine kinase activity was associated with FcepsilonRI in sphingolipid-enriched rafts of mast cells. Bone marrow-derived mast cells from Lyn(-/)(-) mice, compared to syngeneic wild-type cells, were defective in the initial induction of SPHK1 activity, and the defect was overcome by retroviral Lyn expression. These findings position the activation of SPHK1 as an FcepsilonRI proximal event.