Glycobiology Advance Access published online on October 9, 2003
Glycobiology, doi:10.1093/glycob/cwh013
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2003 Oxford University Press
ORIGINAL ARTICLES
1 Department of Biochemistry, Osaka University Graduate School of Medicine, B1, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Revised on September 26, 2003
Accepted on September 29, 2003
Addition of
1-6 GlcNAc branching to the oligosaccharide attached to Asn 772 in the serine protease domain of matriptase plays a pivotal role in its stability and resistance against trypsin
2 Department of Biochemistry, Osaka University Graduate School of Medicine, B1, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Molecular Biochemistry & Clinical Investigations, Osaka University Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan
3 Department of Molecular Biochemistry & Clinical Investigations, Osaka University Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan
4 Department of Oncology, Lombardi Cancer Center, Georgetown University, Medical Center, Washington, DC 20007, USA
1-6 GlcNAc branching, a product of N-acetylglucosaminyltransferase V (GnT-V) is a key structure that is associated with malignant transformations and cancer metastasis. While a number of reports concerning tumor metastasis-related glycoproteins that contain 1-6 GlcNAc branching have appeared, the precise function of 1-6 GlcNAc branching on glycoproteins remains to be elucidated. We previously reported on the importance of 1-6 GlcNAc branching on matriptase in terms of proteolytic degradation in tumor metastasis. Here we report that matriptase purified from GnT-V transfectant (1-6 GlcNAc matriptase), binds strongly to L4-PHA, which preferentially recognizes 1-6 GlcNAc branches of tri- or tetra- antennary sugar chains, indicating that the isolated matriptase contains 1-6 GlcNAc branching. The 1-6 GlcNAc matriptase was resistant to auto-degradation, as well as to trypsin digestion, compared with matriptase purified from mock transfected cells. Furthermore, N-glycosidase-F treatment of 1-6 GlcNAc matriptase greatly reduced its the resistance to degradation. An analysis of matriptase mutants that do not contain potential N-glycosylation sites clearly show that the 1-6 GlcNAc branching on N-glycans attached to Asn 772 in the serine protease domain plays a major role in trypsin resistance. This is the first example of a demonstration of a direct relationship between 1-6 GlcNAc branching and a biological function at the protein level.
GnT-V, protease, matriptase, 1-6 GlcNAc branching
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M.-S. Lee, I-C. Tseng, Y. Wang, K.-i. Kiyomiya, M. D. Johnson, R. B. Dickson, and C.-Y. Lin Autoactivation of matriptase in vitro: requirement for biomembrane and LDL receptor domain Am J Physiol Cell Physiol, July 1, 2007; 293(1): C95 - C105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ihara, Y. Ikeda, S. Toma, X. Wang, T. Suzuki, J. Gu, E. Miyoshi, T. Tsukihara, K. Honke, A. Matsumoto, et al. Crystal structure of mammalian {alpha}1,6-fucosyltransferase, FUT8 Glycobiology, May 1, 2007; 17(5): 455 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-i. Kiyomiya, M.-S. Lee, I-C. Tseng, H. Zuo, R. J. Barndt, M. D. Johnson, R. B. Dickson, and C.-Y. Lin Matriptase activation and shedding with HAI-1 is induced by steroid sex hormones in human prostate cancer cells, but not in breast cancer cells Am J Physiol Cell Physiol, July 1, 2006; 291(1): C40 - C49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Watanabe, H. Ihara, E. Miyoshi, K. Honke, N. Taniguchi, and T. Taguchi A specific detection of GlcNAc{beta}1-6Man{alpha}1 branches in N-linked glycoproteins based on the specificity of N-acetylglucosaminyltransferase VI Glycobiology, May 1, 2006; 16(5): 431 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ito, A. Akinaga, K. Yamanaka, T. Nakagawa, A. Kondo, R. B. Dickson, C.-Y. Lin, A. Miyauchi, N. Taniguchi, and E. Miyoshi Co-expression of matriptase and N-acetylglucosaminyltransferase V in thyroid cancer tissues--its possible role in prolonged stability in vivo by aberrant glycosylation Glycobiology, May 1, 2006; 16(5): 368 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. F. Siddiqui, J. Pawelek, T. Handerson, C.-Y. Lin, R. B. Dickson, D. L. Rimm, and R. L. Camp Coexpression of {beta}1,6-N-Acetylglucosaminyltransferase V Glycoprotein Substrates Defines Aggressive Breast Cancers with Poor Outcome Cancer Epidemiol. Biomarkers Prev., November 1, 2005; 14(11): 2517 - 2523. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Handerson, R. Camp, M. Harigopal, D. Rimm, and J. Pawelek {beta}1,6-Branched Oligosaccharides Are Increased in Lymph Node Metastases and Predict Poor Outcome in Breast Carcinoma Clin. Cancer Res., April 15, 2005; 11(8): 2969 - 2973. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-S. Lee, K.-i. Kiyomiya, C. Benaud, R. B. Dickson, and C.-Y. Lin Simultaneous activation and hepatocyte growth factor activator inhibitor 1-mediated inhibition of matriptase induced at activation foci in human mammary epithelial cells Am J Physiol Cell Physiol, April 1, 2005; 288(4): C932 - C941. [Abstract] [Full Text] [PDF]
|
|