HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 18, 18688-18693, April 30, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/18/18688    most recent M401205200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yamaoka, S. Articles by Okazaki, T. Search for Related Content PubMed PubMed Citation Articles by Yamaoka, S. Articles by Okazaki, T. Social Bookmarking                      What's this?

Expression Cloning of a Human cDNA Restoring Sphingomyelin Synthesis and Cell Growth in Sphingomyelin Synthase-defective Lymphoid Cells^*

Shohei Yamaoka, Michihiko Miyaji, Toshiyuki Kitano, Hisanori Umehara, and Toshiro Okazaki

From the Departments of Hematology/Oncology and Clinical Immunology and the Outpatient Oncology Unit, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 6068507, Japan

Sphingomyelin (SM) synthase has been assumed to be involved in both cell death and survival by regulating pro-apoptotic mediator ceramide and pro-survival mediator diacylglycerol. However, its precise functions are ambiguous due to the lack of molecular cloning of SM synthase gene(s). We isolated WR19L/Fas-SM(-) mouse lymphoid cells, which show a defect of SM at the plasma membrane due to the lack of SM synthase activity and resistance to cell death induced by an SM-directed cytolytic protein lysenin. WR19L/Fas-SM(-) cells were also highly susceptible to methyl--cyclodextrin (MCD) as compared with the WR19L/Fas-SM(+) cells, which are capable of SM synthesis. By expression cloning method using WR19L/Fas-SM(-) cells and MCD-based selection, we have succeeded in cloning of a human cDNA responsible for SM synthase activity. The cDNA encodes a peptide of 413 amino acids named SMS1 (putative molecular mass, 48.6 kDa), which contains a sterile motif domain near the N-terminal region and four predicted transmembrane domains. WR19L/Fas-SM(-) cells expressing SMS1 cDNA (WR19L/Fas-SMS1) restored the resistance against MCD, the accumulation of SM at the plasma membrane, and SM synthesis by transferring phosphocholine from phosphatidylcholine to ceramide. Furthermore, WR19L/Fas-SMS1 cells, as well as WR19L/Fas-SM(-) cells supplemented with exogenous SM, restored cell growth ability in serum-free conditions, where the growth of WR19L/Fas-SM(-) cells was severely inhibited. The results suggest that SMS1 is responsible for SM synthase activity in mammalian cells and plays a critical role in cell growth of mouse lymphoid cells.

Received for publication, February 3, 2004

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AB154421.

^* This work was supported by a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel. and Fax: 81-75-751-3154; E-mail: toshiroo{at}kuhp.kyoto-u.ac.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. Tomishige, K. Kumagai, J. Kusuda, M. Nishijima, and K. Hanada Casein Kinase I{gamma}2 Down-Regulates Trafficking of Ceramide in the Synthesis of Sphingomyelin Mol. Biol. Cell, January 1, 2009; 20(1): 348 - 357. [Abstract] [Full Text] [PDF]

				Z.-X. Jin, C.-R. Huang, L. Dong, S. Goda, T. Kawanami, T. Sawaki, T. Sakai, X.-P. Tong, Y. Masaki, T. Fukushima, et al. Impaired TCR signaling through dysfunction of lipid rafts in sphingomyelin synthase 1 (SMS1)-knockdown T cells Int. Immunol., November 1, 2008; 20(11): 1427 - 1437. [Abstract] [Full Text] [PDF]

				T. K. Hailemariam, C. Huan, J. Liu, Z. Li, C. Roman, M. Kalbfeisch, H. H. Bui, D. A. Peake, M.-S. Kuo, G. Cao, et al. Sphingomyelin Synthase 2 Deficiency Attenuates NF{kappa}B Activation Arterioscler. Thromb. Vasc. Biol., August 1, 2008; 28(8): 1519 - 1526. [Abstract] [Full Text] [PDF]

				T. Ding, Z. Li, T. Hailemariam, S. Mukherjee, F. R. Maxfield, M.-P. Wu, and X.-C. Jiang SMS overexpression and knockdown: impact on cellular sphingomyelin and diacylglycerol metabolism, and cell apoptosis J. Lipid Res., February 1, 2008; 49(2): 376 - 385. [Abstract] [Full Text] [PDF]

				D. Halter, S. Neumann, S. M. van Dijk, J. Wolthoorn, A. M. de Maziere, O. V. Vieira, P. Mattjus, J. Klumperman, G. van Meer, and H. Sprong Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis J. Cell Biol., October 8, 2007; 179(1): 101 - 115. [Abstract] [Full Text] [PDF]

				S. Bao, Y. Li, X. Lei, M. Wohltmann, W. Jin, A. Bohrer, C. F. Semenkovich, S. Ramanadham, I. Tabas, and J. Turk Attenuated Free Cholesterol Loading-induced Apoptosis but Preserved Phospholipid Composition of Peritoneal Macrophages from Mice That Do Not Express Group VIA Phospholipase A2 J. Biol. Chem., September 14, 2007; 282(37): 27100 - 27114. [Abstract] [Full Text] [PDF]

				R. P. Rao, C. Yuan, J. C. Allegood, S. S. Rawat, M. B. Edwards, X. Wang, A. H. Merrill Jr., U. Acharya, and J. K. Acharya Ceramide transfer protein function is essential for normal oxidative stress response and lifespan PNAS, July 3, 2007; 104(27): 11364 - 11369. [Abstract] [Full Text] [PDF]

				F. G. Tafesse, K. Huitema, M. Hermansson, S. van der Poel, J. van den Dikkenberg, A. Uphoff, P. Somerharju, and J. C. M. Holthuis Both Sphingomyelin Synthases SMS1 and SMS2 Are Required for Sphingomyelin Homeostasis and Growth in Human HeLa Cells J. Biol. Chem., June 15, 2007; 282(24): 17537 - 17547. [Abstract] [Full Text] [PDF]

				F. G. Tafesse, P. Ternes, and J. C. M. Holthuis The Multigenic Sphingomyelin Synthase Family J. Biol. Chem., October 6, 2006; 281(40): 29421 - 29425. [Full Text] [PDF]

				J. Dong, J. Liu, B. Lou, Z. Li, X. Ye, M. Wu, and X.-C. Jiang Adenovirus-mediated overexpression of sphingomyelin synthases 1 and 2 increases the atherogenic potential in mice J. Lipid Res., June 1, 2006; 47(6): 1307 - 1314. [Abstract] [Full Text] [PDF]

				S. Mitsutake and Y. Igarashi Calmodulin Is Involved in the Ca2+-dependent Activation of Ceramide Kinase as a Calcium Sensor J. Biol. Chem., December 9, 2005; 280(49): 40436 - 40441. [Abstract] [Full Text] [PDF]

				M. Miyaji, Z.-X. Jin, S. Yamaoka, R. Amakawa, S. Fukuhara, S. B. Sato, T. Kobayashi, N. Domae, T. Mimori, E. T. Bloom, et al. Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis J. Exp. Med., July 18, 2005; 202(2): 249 - 259. [Abstract] [Full Text] [PDF]

				A. Kihara and Y. Igarashi FVT-1 Is a Mammalian 3-Ketodihydrosphingosine Reductase with an Active Site That Faces the Cytosolic Side of the Endoplasmic Reticulum Membrane J. Biol. Chem., November 19, 2004; 279(47): 49243 - 49250. [Abstract] [Full Text] [PDF]

				Y. Uchida, M. Itoh, Y. Taguchi, S. Yamaoka, H. Umehara, S.-i. Ichikawa, Y. Hirabayashi, W. M. Holleran, and T. Okazaki Ceramide Reduction and Transcriptional Up-Regulation of Glucosylceramide Synthase through Doxorubicin-Activated Sp1 in Drug-Resistant HL-60/ADR Cells Cancer Res., September 1, 2004; 64(17): 6271 - 6279. [Abstract] [Full Text] [PDF]