Early activation of sphingosine kinase in mast cells and recruitment to FcepsilonRI are mediated by its interaction with Lyn kinase.
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.
Urtz
Nicole
N
Novartis Institute for Biomedical Research, Brunner Strasse 59, A-1235 Vienna, Austria.
Olivera
Ana
A
Bofill-Cardona
Elisa
E
Csonga
Robert
R
Billich
Andreas
A
Mechtcheriakova
Diana
D
Bornancin
Frederic
F
Woisetschläger
Max
M
Rivera
Juan
J
Baumruker
Thomas
T
D000818:Animals; D006367:HeLa Cells; D006801:Humans; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism*; D013997:Time Factors; D019061:src-Family Kinases / Q000378:metabolism*; D000099157:Sphingosine Kinase
D017853:Phosphotransferases (Alcohol Group Acceptor); D017455:Receptors, IgE; D019061:src-Family Kinases; D000099157:Sphingosine Kinase; C060902:lyn protein-tyrosine kinase