J. Biochem, 2003, Vol. 134, No. 5 667-673
© 2003 Japanese Biochemical Society
BIOCHEMISTRY |
Truncation of the N-Terminal Ectodomain Has Implications in the N-Glycosylation and Transport to the Cell Surface of Edg-1/S1P1 Receptor
Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Nishi 6, Kita 12, Kita-ku, Sapporo 060-0812
The endothelial cell-expressed sphingosine 1-phosphate receptors Edg-1/S1P1 and Edg-3/S1P3 have been implicated in various physiological events such as the regulation of angiogenesis. Since there is an excess of a ligand constitutively in blood, these receptors may have some mechanism(s) avoiding overstimulation. In this study, we found that the N-terminal ectodomains of Edg-1/S1P1 and Edg-3/S1P3 were truncated in overexpressing cells. The truncated form of Edg-1/S1P1 expressed on the cell surface had undergone complex-type oligosaccharide modification at the Golgi. A deletion mutant lacking the N-terminal processing domain of Edg-1/S1P1 accumulated in the endoplasmic reticulum, and was not expressed on the cell surface. When a basic amino acid residue was introduced at the cleavage site of Edg-1/S1P1, the molecular weight of the glycosylated protein was greater in the mutant compared to the wild type, due to the bound oligosaccharide. These results demonstrated that the structure of the N-terminal ectodomain of Edg-1/S1P1 affects both its transport to the cell surface and the N-glycosylation process. Ectodomain shedding of many membrane proteins has been implicated in various diseases. Therefore, N-terminal processing of Edg-1/S1P1 and Edg-3/S1P3 might play roles in endothelial cell functions.
* To whom correspondence should be addressed. Tel: +81-11-706-3970, Fax: +81-11-706-4986, E-mail: yigarash{at}pharm.hokudai.ac.jp
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Q. Deng, J. A. Clemas, G. Chrebet, P. Fischer, J. J. Hale, Z. Li, S. G. Mills, J. Bergstrom, S. Mandala, R. Mosley, et al. Identification of Leu276 of the S1P1 Receptor and Phe263 of the S1P3 Receptor in Interaction with Receptor Specific Agonists by Molecular Modeling, Site-Directed Mutagenesis, and Affinity Studies Mol. Pharmacol., March 1, 2007; 71(3): 724 - 735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-P. Fortin, E. K. Dziadulewicz, L. Gera, and F. Marceau A Nonpeptide Antagonist Reveals a Highly Glycosylated State of the Rabbit Kinin B1 Receptor Mol. Pharmacol., April 1, 2006; 69(4): 1146 - 1157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. I. Singer, M. Tian, L. A. Wickham, J. Lin, S. S. Matheravidathu, M. J. Forrest, S. Mandala, and E. J. Quackenbush Sphingosine-1-Phosphate Agonists Increase Macrophage Homing, Lymphocyte Contacts, and Endothelial Junctional Complex Formation in Murine Lymph Nodes J. Immunol., December 1, 2005; 175(11): 7151 - 7161. [Abstract] [Full Text] [PDF]
|
|