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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4736-4742. Prepublished online as a Blood First Edition Paper on March 1, 2005; DOI 10.1182/blood-2004-12-4686. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-12-4686v1 105/12/4736    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jolly, P. S. Articles by Spiegel, S. Search for Related Content PubMed PubMed Citation Articles by Jolly, P. S. Articles by Spiegel, S. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Expression of SphK1 impairs degranulation and motility of RBL-2H3 mast cells by desensitizing S1P receptors Puneet S. Jolly, Meryem Bektas, Kenneth R. Watterson, Heidi Sankala, Shawn G. Payne, Sheldon Milstien, and Sarah Spiegel From the Department of Biochemistry, Virginia Commonwealth University School of Medicine, Richmond, VA; Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC; and National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD. Mast cells play a central role in inflammatory and immediate-type allergic reactions by secreting a variety of biologically active substances, including sphingosine-1 phosphate (S1P). Sphingosine kinase 1 (SphK1) and formation of S1P, which leads to transactivation of S1P receptors and their downstream signaling pathways, regulates mast-cell functions initiated by cross-linking of the high-affinity immunoglobulin E (IgE) receptor FcRI. Surprisingly, overexpression of SphK1 in rat basophilic leukemia (RBL)-2H3 mast cells impaired degranulation as well as migration toward antigen. These effects were reversed by serum withdrawal, yet the increased formation and secretion of S1P were the same as in the presence of serum. Nonetheless, serum increased localization of SphK1 at the plasma membrane. This restricted formation of S1P induced internalization and desensitization of S1P receptors on the surface of mast cells as determined by confocal immunofluorescence microscopy, aberrant S1P receptor signaling, and lack of S1P receptor coupling to G proteins. Serum starvation, which significantly reduced membrane-associated SphK1 activity, restored S1P receptor functions. Our results have important implications for mast-cell migration and degranulation as well as for the biologic functions of the S1P receptors on cells that are circulating in the bloodstream. (Blood. 2005;105:4736-4742) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. A. Oskeritzian, S. E. Alvarez, N. C. Hait, M. M. Price, S. Milstien, and S. Spiegel Distinct roles of sphingosine kinases 1 and 2 in human mast-cell functions Blood, April 15, 2008; 111(8): 4193 - 4200. [Abstract] [Full Text] [PDF] Y. Kurashima, J. Kunisawa, M. Higuchi, M. Gohda, I. Ishikawa, N. Takayama, M. Shimizu, and H. Kiyono Sphingosine 1-Phosphate-Mediated Trafficking of Pathogenic Th2 and Mast Cells for the Control of Food Allergy J. Immunol., August 1, 2007; 179(3): 1577 - 1585. [Abstract] [Full Text] [PDF] P. Hanel, P. Andreani, and M. H. Graler Erythrocytes store and release sphingosine 1-phosphate in blood FASEB J, April 1, 2007; 21(4): 1202 - 1209. [Abstract] [Full Text] [PDF] S. G. Payne, C. A. Oskeritzian, R. Griffiths, P. Subramanian, S. E. Barbour, C. E. Chalfant, S. Milstien, and S. Spiegel The immunosuppressant drug FTY720 inhibits cytosolic phospholipase A2 independently of sphingosine-1-phosphate receptors Blood, February 1, 2007; 109(3): 1077 - 1085. [Abstract] [Full Text] [PDF] D. Leiber, Y. Banno, and Z. Tanfin Exogenous sphingosine 1-phosphate and sphingosine kinase activated by endothelin-1 induced myometrial contraction through differential mechanisms Am J Physiol Cell Physiol, January 1, 2007; 292(1): C240 - C250. [Abstract] [Full Text] [PDF] P. Mitra, C. A. Oskeritzian, S. G. Payne, M. A. Beaven, S. Milstien, and S. Spiegel Role of ABCC1 in export of sphingosine-1-phosphate from mast cells PNAS, October 31, 2006; 103(44): 16394 - 16399. [Abstract] [Full Text] [PDF] R. Xu, J. Jin, W. Hu, W. Sun, J. Bielawski, Z. Szulc, T. Taha, L. M. Obeid, and C. Mao Golgi alkaline ceramidase regulates cell proliferation and survival by controlling levels of sphingosine and S1P FASEB J, September 1, 2006; 20(11): 1813 - 1825. [Abstract] [Full Text] [PDF] N. F. Lamour and C. E. Chalfant Ceramide-1-phosphate: The "missing" link in eicosanoid biosynthesis and inflammation Mol. Interv., December 1, 2005; 5(6): 358 - 367. [Abstract] [Full Text] [PDF] C. E. Chalfant and S. Spiegel Sphingosine 1-phosphate and ceramide 1-phosphate: expanding roles in cell signaling J. Cell Sci., October 15, 2005; 118(20): 4605 - 4612. [Abstract] [Full Text] [PDF]

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