This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Urtz, N. Articles by Baumruker, T. Search for Related Content PubMed PubMed Citation Articles by Urtz, N. Articles by Baumruker, T.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2004, p. 8765-8777, Vol. 24, No. 19
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.19.8765-8777.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Early Activation of Sphingosine Kinase in Mast Cells and Recruitment to FcRI Are Mediated by Its Interaction with Lyn Kinase

Novartis Institute for Biomedical Research Vienna, Vienna, Austria,¹ Molecular Immunology and Inflammation Branch, National Institutes of Health, Bethesda, Maryland²

Received 28 January 2004/ Returned for modification 1 April 2004/ Accepted 6 July 2004

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 Ca²⁺, released from internal stores, and to degranulation. These events either precede or are concomitant with the activation of phospholipase C- 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 (FcRI). The interaction of SPHK1 with Lyn caused enhanced lipid and tyrosine kinase activity. After FcRI triggering, enhanced sphingosine kinase activity was associated with FcRI 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 FcRI proximal event.

This article has been cited by other articles:

• Oskeritzian, C. A., Alvarez, S. E., Hait, N. C., Price, M. M., Milstien, S., Spiegel, S. (2008). Distinct roles of sphingosine kinases 1 and 2 in human mast-cell functions. Blood 111: 4193-4200 [Abstract] [Full Text]  
• Leclercq, T. M., Moretti, P. A. B., Vadas, M. A., Pitson, S. M. (2008). Eukaryotic Elongation Factor 1A Interacts with Sphingosine Kinase and Directly Enhances Its Catalytic Activity. J. Biol. Chem. 283: 9606-9614 [Abstract] [Full Text]  
• Hait, N. C., Bellamy, A., Milstien, S., Kordula, T., Spiegel, S. (2007). Sphingosine Kinase Type 2 Activation by ERK-mediated Phosphorylation. J. Biol. Chem. 282: 12058-12065 [Abstract] [Full Text]  
• Mitra, P., Oskeritzian, C. A., Payne, S. G., Beaven, M. A., Milstien, S., Spiegel, S. (2006). Role of ABCC1 in export of sphingosine-1-phosphate from mast cells. Proc. Natl. Acad. Sci. USA 103: 16394-16399 [Abstract] [Full Text]  
• Olivera, A., Urtz, N., Mizugishi, K., Yamashita, Y., Gilfillan, A. M., Furumoto, Y., Gu, H., Proia, R. L., Baumruker, T., Rivera, J. (2006). IgE-dependent Activation of Sphingosine Kinases 1 and 2 and Secretion of Sphingosine 1-Phosphate Requires Fyn Kinase and Contributes to Mast Cell Responses. J. Biol. Chem. 281: 2515-2525 [Abstract] [Full Text]  
• Olivera, A., Rivera, J. (2005). Sphingolipids and the Balancing of Immune Cell Function: Lessons from the Mast Cell. J. Immunol. 174: 1153-1158 [Abstract] [Full Text]